Biomedical subjects

M D Taylor

Publications and source records attributed to M D Taylor.

95 records · Page 6Linked to original sources

PubMedDate not supplied

Transplacental pharmacokinetics of flecainide in the gravid baboon and fetus.

The objective of this study was to characterize the transfer of flecainide across the placenta and determine the fetal: maternal ratio of flecainide in the gravid baboon. Flecainide acetate has been especially successful for the treatment of fetal supraventricular tachycardia associated with hydrops fetalis. However, the degree of transplacental transmission remains unknown. In this study, all animals were placed under general anesthesia. Flecainide 2.5 mg/kg was administered intravenously. Percutaneous umbilical blood sampling was performed simultaneously with maternal sampling. Flecainide levels were measured using high-performance liquid chromatography with ultraviolet detection. A total of six gravid baboons were studied at an average gestational age of 132 days. The mean maternal volume of distribution at steady state was 5.1 +/- 1.8 L/kg. The mean combined elimination constant (k(el)) was 0.79 +/- 0.19 hr(-1) [95% confidence interval (CI), 0.64-0.93]. There was a linear relationship between maternal and fetal concentrations, with a ratio of fetal-to-maternal serum levels of 0.49 +/- 0.05 (95% CI, 0.39-0.59). At steady state, fetal flecainide levels are approximately 50% of maternal flecainide levels. Flecainide is rapidly distributed in the mother and fetus following a single intravenous dose with a maternal volume of distribution similar to that reported in normal healthy human adults. Since fetal levels correlate closely with maternal levels, we propose that it is possible to estimate fetal levels by monitoring maternal levels.

Animals↗

PubMedDate not supplied

Low grip strength, impaired tongue force and hyperactivity induced by overexpression of neurotrophin-3 in mouse skeletal muscle.

Transgenic mice overexpressing neurotrophin-3 (NT-3) in skeletal muscle (mlc/NT-3 mice) develop abnormal muscle spindles in skeletal muscle and display abnormal motor function in the form of gait and locomotive disturbances. The purpose of this work was to characterize the functional consequences of NT-3 overexpression in skeletal muscle with further behavioral assessments that permitted inferences about muscle weakness in the tongue or forelimbs as well as potential central nervous system (CNS) abnormalities compared to wild-type controls. Wild-type (n=12) and mlc/NT-3 (n=12) male mice were tested in five procedures (in chronological order): lick dynamics, locomotor activity, grid ataxia, go-no-go discrimination procedure, and grip strength. Relative to wild-type mice, the mlc/NT-3 mice exhibited lower tongue force, hyperactivity, slowed limb retrieval in the grid ataxia test, similar discrimination performance, and lower grip strength. Overall, the data suggest that chronically elevated levels of NT-3 in mouse skeletal muscle cause muscle weakness in the mlc/NT-3 mice. Surprisingly, mlc/NT-3 mice also exhibited significant hyperactivity, suggesting that NT-3 overexpression in the periphery may have caused abnormalities in the CNS that are related to the cortical processing of proprioceptive afferent information.

Afferent Pathways↗

PubMedDate not supplied

Protective action by methylprednisolone, allopurinol and indomethacin against stroke-induced damage to adenylate cyclase in gerbil cerebral cortex.

Adenylate cyclase activity was investigated in either homogenate or particulate fractions from the frontal cerebral cortex of the gerbil following five experimental conditions of bilateral ischemia. After periods of 15 min ischemia, 15 min ischemia plus 15 min of recirculation or 60 min ischemia the enzyme generally displayed enhanced responses to GTP, norepinephrine (NE), dopamine (DA), NE + GTP and DA + GTP. Pretreatment of the gerbils with methylprednisolone, allopurinol or indomethacin did not significantly influence the outcome of these findings. When the animals were subjected to 60 min ischemia plus 15 min of reflow, enzyme responses to the stimulatory agents including forskolin and NaF were all reduced. Pretreatment with methylprednisolone, allopurinol or indomethacin prevented the damage to adenylate cyclase in the 60 min ischemia plus 15 min reflow animals. When animals were made ischemic for 15 min followed by one week of recovery, enzyme sensitivity to GTP, calmodulin-Ca++, NE, combinations thereof and forskolin were reduced in only the particulate fractions. Enzyme damage was reversed following methylprednisolone. Enzyme damage may result from generation of free radicals during reflow and drugs that either inhibit synthesis pathways generating free radicals, stabilize cell membranes or act as free radical scavengers may be therapeutically beneficial under specific conditions of stroke.

Adenylyl Cyclases↗

PubMedDate not supplied

Mechanisms of nutrient attenuation in a subsurface flow riparian wetland.

Riparian wetlands are transition zones between terrestrial and aquatic environments that have the potential to serve as nutrient filters for surface and ground water due to their topographic location. We investigated a riparian wetland that had been receiving intermittent inputs of NO3- and PO4(3-) during storm runoff events to determine the mechanisms of nutrient attenuation in the wetland soils. Few studies have shown whether infrequent pulses of NO3- are sufficient to maintain substantial denitrifying communities. Denitrification rates were highest at the upstream side of the wetland where nutrient-rich runoff first enters the wetland (17-58 microg N2O-N kg soil(-1) h(-1)) and decreased further into the wetland. Carbon limitation for denitrification was minor in the wetland soils. Samples not amended with dextrose had 75% of the denitrification rate of samples with excess dextrose C. Phosphate sorption isotherms suggested that the wetland soils had a high capacity for P retention. The calculated soil PO4(3-) concentration that would yield an equilibrium aqueous P04(3-) concentration of 0.05 mg P L(-1) was found to be 100 times greater than the soil PO4(3-) concentration at the time of sampling. This indicated that the wetland could retain a large additional mass of PO4(3-) without increasing the dissolved P04(3-) concentrations above USEPA recommended levels for lentic waters. These results demonstrated that denitrification can be substantial in systems receiving pulsed NO3- inputs and that sorption could account for extensive PO4(3-) attenuation observed at this site.

Adsorption↗

PubMedDate not supplied

Land application of domestic effluent onto four soil types: plant uptake and nutrient leaching.

Land application has become a widely applied method for treating wastewater. However, it is not always clear which soil-plant systems should be used, or why. The objectives of our study were to determine if four contrasting soils, from which the pasture is regularly cut and removed, varied in their ability to assimilate nutrients from secondary-treated domestic effluent under high hydraulic loadings, in comparison with unirrigated, fertilized pasture. Grassed intact soil cores (500 mm in diameter by 700 mm in depth) were irrigated (50 mm wk(-1)) with secondary-treated domestic effluent for two years. Soils included a well-drained Allophanic Soil (Typic Hapludand), a poorly drained Gley Soil (Typic Endoaquept), a well-drained Pumice Soil formed from rhyolitic tephra (Typic Udivitrand), and a well-drained Recent Soil formed in a sand dune (Typic Udipsamment). Effluent-irrigated soils received between 746 and 815 kg N ha(-1) and 283 and 331 kg P ha(-1) over two years of irrigation, and unirrigated treatments received 200 kg N ha(-1) and 100 kg P ha(-1) of dissolved inorganic fertilizer over the same period. Applying effluent significantly increased plant uptake of N and P from all soil types. For the effluent-irrigated soils plant N uptake ranged from 186 to 437 kg N ha(-1) yr(-1), while plant P uptake ranged from 40 to 88 kg P ha(-1) yr(-1) for the effluent-irrigated soils. Applying effluent significantly increased N leaching losses from Gley and Recent Soils, and after two years ranged from 17 to 184 kg N ha(-1) depending on soil type. Effluent irrigation only increased P leaching from the Gley Soil. All P leaching losses were less than 49 kg P ha(-1) after two years. The N and P leached from effluent treatments were mainly in organic form (69-87% organic N and 35-65% unreactive P). Greater N and P leaching losses from the irrigated Gley Soil were attributed to preferential flow that reduced contact between the effluent and the soil matrix. Increased N leaching from the Recent Soil was the result of increased leaching of native soil organic N due to the higher hydraulic loading from the effluent irrigation.

Agriculture↗