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Biomedical subjects

D Freeman

Publications and source records attributed to D Freeman.

11 recordsLinked to original sources
PubMed2026

Addressing the dual-use of antifungals and fungal antimicrobial resistance (fAMR) through a One Health approach.

Fungal antimicrobial resistance (fAMR) is accelerating, driven in part by the dual-use of antifungal modes of action in agriculture and medicine, threatening therapy. Addressing this challenge requires a unified One Health response that balances agricultural productivity, economic stability, and human and animal health. By focusing on the United Kingdom's policy approach, we argue that current efforts are constrained by fragmented governance, surveillance and regulation. To resolve this, we propose three policy recommendations: 1. a cross-government fAMR body, 2. mandatory environmental and clinical surveillance, and 3. for fungicide approvals to look beyond crop pathogens and integrate risk assessments for potential hotspots of resistance selection in human fungal pathogens. These measures will safeguard current and future antifungals while providing much-needed regulatory clarity and will be translatable to other national and regional contexts.

Journal Article↗
PubMed1992

Simultaneous solid-phase extraction and chromatographic analysis of morphine and hydromorphone in plasma by high-performance liquid chromatography with electrochemical detection.

High-performance liquid chromatography has become an important analytical tool for the quantitation of opioid drugs. Using solid-phase extraction and coulometric electrochemical detection, we have developed a chromatographic method for the simultaneous measurement of morphine and hydromorphone which is both sensitive and specific. Using 1 ml of plasma, intra-assay and inter-assay data show that the detection limit for accurate quantitation of these compounds is about 1.2 ng/ml (coefficient of variation 11.6%) for morphine and 2.5 ng/ml (coefficient of variation 10.5%) for hydromorphone. The method is simple and readily adaptable to most pharmacokinetic studies and toxic screens involving these drugs.

Chromatography, High Pressure Liquid↗
PubMed1992

Differences in metabolism of time-release and unmodified nicotinic acid: explanation of the differences in hypolipidemic action?

The possibility that differences in metabolism might underly the differences in efficacy and toxicity between time-release and unmodified formulations of nicotinic acid was investigated by measuring 24-hour urinary excretion of metabolites in 10 subjects who received both forms. Nicotinic acid has two metabolic fates: formation of nicotinamide adenine dinucleotide (NAD) and formation of nicotinuric acid, the glycine conjugate of nicotinic acid. Catabolism of NAD releases nicotinamide, which is subsequently methylated and/or oxidized to form a number of metabolites, with 2-pyridone predominating. Excretion of nicotinuric acid was more than four times greater when subjects took unmodified nicotinic acid than when they took time-release nicotinic acid (78.2 and 18.8 mg, respectively). In contrast, excretion of 2-pyridone with unmodified nicotinic acid was only 30% more than with time-release nicotinic acid (171.0 and 129.9 mg, respectively). These results demonstrate a marked difference in the metabolism of unmodified and time-release nicotinic acid. It is proposed that nicotinyl coenzyme A (CoA), the metabolic intermediate in the formation of nicotinuric acid, mediates some of the hypolipidemic actions of nicotinic acid, as the acyl-CoA esters of xenobiotics, including clofibrate, have been shown to interfere with lipid metabolism.

Adult↗
PubMed1991

Proton editing and imaging of lactate.

Highly specific NMR assays for the detection, quantitation and imaging of lactate in vivo are described. Applications in animals include tumor monitoring, the determination of hypoxic cell distribution and the demonstration of the efficacy of tumor-sensitizers. The methods (GE-DQCOSY and GE-HMQC) may be particularly useful in heteronuclear NMR in vivo.

Animals↗
PubMed1978

Synthesis of 1 alpha-hydroxy[7-3H]cholecalciferol and its metabolism in the chick.

1. 1 alpha-Hydroxy[7-3H]cholecalciferol (specific radioactivity of 2-Ci/mmol) was synthesized, and its metabolism in chicks studied. 2. 1 alpha-Hydroxy[7-3H]cholecalciferol was metabolized very rapidly in the chick to 1 alpha,25-dihydroxy[7-3H]cholecalciferol and to a metabolite less polar than 1 alpha-hydroxycholecalciferol. Intestine exhibited highest accumulation of 1 alpha-25-dihydroxy[7-3H]cholecalciferol, and liver exhibited highest accumulation of the non-polar metabolite. 3. Tissue uptake of 1 alpha-hydroxy[7-3H]cholecalciferol and its metabolites in chicks that were dosed continuously for 16 days with 1 alpha-hydroxy[7-3H]cholecalciferol did not exceed by very much that observed in tissues obtained from chicks that were dosed with a single injection of 1 alpha-hydroxy[7-3H]cholecalciferol 24 h before killing, except for liver and kidney. 4. Lowest accumulation of metabolites was noted in muscle and bone, and for the latter, highest uptake of 1 alpha,25-dihydroxy[7-3H]cholecalciferol was noted in the epiphysial periosteum and the metaphysis. 5. Formation of 1 alpha,24,25-trihydroxy[7-3H]cholecalciferol was not observed in the chicks that were dosed continuously with 1 alpha-hydroxy[7-3H]cholecalciferol, despite the fact that plasma calcium and phosphorus were normal and despite the presence of renal 24-hydroxylase activity. 6. The vitamin D status of the chicks did not appear to affect the metabolic profile of the administered 1 alpha-hydroxy[7-3H]cholecalciferol.

Animals↗
PubMed1977

Binding and biologic activity of glucagon in liver cell membranes of chronically hyperglucagonemic rats.

Glucagon binding by liver cell membranes was examined in rats with chronically elevated plasma levels of immunoreactive glucagon (IRG) resulting from insulin deficiency, starvation, or twice daily glucagon injections. The concentration of specific glucagon binding sites was significantly reduced in the three chronically hyperglucagonemic (IRG greater than 125 pg/ml) groups as compared with nondiabetic controls and insulin-treated diabetic control rats with only mild hyperglucagonemia. A reduction in glucagon binding sites did not occur with hyperglucagonemia of 12 h or less. Despite the reduced binding of glucagon in the three chronically hyperglucagonemic groups, the ability of glucagon to stimulate cAMP production was not reduced. It is concluded that while decreased glucagon binding occures in the forms of chronic hyperglucagonemia studied, it is not associated with a reduction in the ability of glucagon to stimulate cAMP production.

Adenylyl Cyclases↗
PubMed1975

Hematology and blood chemistry in saturation diving: I. Antiplatelet drugs, aspirin, and VK744.

Blood chemistry and cellular parameters were studied before, during, and after saturation (2.4 ATA) dives in the HYDRO-LAB habitat on two separate occasions. In both, platelet count fell greater than 20% 12-24 hours after surfacing and moderate (5%) reductions in hemoglobin, red-cell count, and packed-cell volume were observed. Plasma cholesterol and triglyceride levels were depressed postdive as were most plasma enzymes (GOT, GPT, CPK, LDH, ALP). The latter changes were very slight. In the first study, the incidental ingestion of aspirin by some divers did not prevent the loss of platelets even though the platelet-release reaction in response to ADP was inhibited. In the second study the platelet-suppressive drug VK744 was administered, on a double-blind randomized basis, to six divers, six others taking a placebo capsule. Dosage of VK744 was 300 mg TID for 2 days before, 5 days during, 3 days after saturation dive. The drug inhibited the postdive loss of circulatory platelets and in fact the treated group showed a rebound in platelet count above control values, 48-72 hours postdive. Megathrombocyte counts indicated the production of new platelets in both groups at this point. The treated group also showed a marked and significant reduction in plasma cholesterol and triglycerides, suggesting an antilipidemic effect of the drug. Theses results confirm previous observations and indicate that postdecompression loss of platelets may be related to sequestering of reactive platelets, possibly by microbubbles, and that the phenomenon can be inhibited by some antiplatelet drugs.

Adult↗
PubMed1975

Hematology and blood chemistry in saturation diving: II. Open-sea vs. hyperbaric chamber.

Hematograms, platelet function, and blood-enzyme chemistry were compared in two similar saturation-excursion dives, one conducted in a hyperbaric chamber and the other in the open sea. The chamber dive was more stressful in that it was preceded by a series of bounce decompression dives (one of which produced a 100% incidence of cutaneous pruritus in four subjects) and in that the excursions from saturation depth (60 fsw or 2.818 ATA) were longer and deeper (producing one case of O2 convulsions, one of confirmed decompression sickness, and several of Doppler-detected vascular bubbles). The chamber dive was associated with a marked and significant reduction in circulating platelet count; significant increases in plasma enzyme activities in the victim of O2 toxicity (LDH, CPK) and in one subject with Doppler bubbles and questionable bends symptoms (LDH, GOT, GPT) but not in another; and mild but significant anemia. In the open-water dive, one subject, who developed symptoms of gastroenteritis, showed moderate elevation of LDH, GOT, and GPT activity. No significant change in platelet counts occurred. Both dives were associated with elevated white-cell counts, apparently as a result of numerous minor infections, and reduced sensitivity of platelets of ADP-induced aggregation.

Alanine Transaminase↗