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Biomedical subjects

J Wiegand

Publications and source records attributed to J Wiegand.

45 records · Page 3Linked to original sources

A comparison of the iron-clearing properties of 1,2-dimethyl-3-hydroxypyrid-4-one, 1,2-diethyl-3-hydroxypyrid-4-one, and deferoxamine.

A comparative study of the iron-clearing properties of subcutaneously (SC) administered deferoxamine (DFO) with those of orally administered 1,2-dimethyl-3-hydroxypyrid-4-one (CP20) and 1,2-diethyl-3-hydroxypyrid-4-one (CP94) is presented. The studies were performed in both a non-iron-overloaded, bile duct-cannulated rat model and an iron-loaded Cebus monkey model. All three drugs performed well in the rodent, promoting the excretion of iron in both the urine and the bile, with total iron output efficiencies of 2.8%, 1.2%, and 7.1%, respectively. The efficiency of DFO increased slightly in the Cebus model, while that of the hydroxypyridones was essentially the same in the monkey, with total iron output efficiencies of 5.5%, 2.1%, and 7.4%, respectively. Iron balance studies showed that both DFO and CP94 were able to maintain the animals in a negative iron balance, while CP20 had little impact.

Animals↗

Synovial and serum levels of triamcinolone following intra-articular administration of triamcinolone acetonide in the horse.

Seven mature thoroughbred horses, weighing between 400 and 541 kg, were each injected intra-articularly into three joints with 6 mg/joint of triamcinolone acetonide (Vetalog). The fourth joint, the control, was injected with saline. Synovial fluid was taken from all four legs of the horses on days 1, 2, 3, 4, 5, 6, 7, 8, 11, and 15 following the injections. Triamcinolone acetonide was assayed by a radioimmunoassay. Blood was collected at 1, 2, 4, 6, 12 h and on days 1, 2, 3, 4, 5, 6, 7, 8, 11, and 15 following injection of either triamcinolone or saline. Both cortisol and triamcinolone were assayed. The results show that the synovial fluid level of triamcinolone was 7.5 micrograms/ml 1 day following treatment and decreased to 10 ng/ml by the 4th day. These low levels were maintained for approximately 14 days. By the 15th day, the triamcinolone was below a detectable level. Serum levels of triamcinolone increased to 3 ng/ml within 1 h and further increased to a peak of 4.3 ng/ml at 4th h. The level then decreased to 2 ng/ml at 24 h and to nearly an undetectable level in 48 h. The mean level of serum cortisol, on the other hand, gradually decreased as the serum level of triamcinolone increased. As the serum level of triamcinolone reached an undetectable level on the 2nd day, the serum cortisol level gradually increased and returned to the pre-administration level by the 5th day. These results showed that the intra-articular administration of triamcinolone maintained triamcinolone in the synovial fluid for 4-14 days and that the triamcinolone reached the blood within 1 h. The serum level of triamcinolone was maintained for 2 days and resulted in the inhibition of adrenal function for 4 days.

Animals↗

Evaluation of desferrithiocin and its synthetic analogues as orally effective iron chelators.

Desferrithiocin, a novel microbial siderophore isolated from cultures of Streptomyces antibioticus DSM 1865, and a number of its derivatives and analogues are evaluated for their ability to promote iron clearance. The compounds have been designed with the objective of identifying the structural features of desferrithiocin which render this ligand an orally effective iron chelator. The desferrithiocin aromatic hydroxyl and the thiazoline ring carboxyl group are shown to be central to desferrithiocin's activity. The ligand's methyl and the aromatic nitrogen play little role in the compound's efficacy. The animal model chosen for this study, the bile duct cannulated rat, provides information regarding both the chelator-induced total iron output and the kinetics of both biliary and urinary iron excretion.

Administration, Oral↗

Synthesis and biological evaluation of hydroxamate-based iron chelators.

A new and versatile route to desferrioxamine B (DFO, 1) is described. Hydroxamate reagent 4 was elaborated in a series of high yield steps to the tert-butoxycarbonyl nitrile 11, which provided DFO in three transformations. The intermediate 11 could also be utilized in the preparation of DFO analogues which contain terminal N-acyl groups other than acetyl. The methodology was further employed in the syntheses of the DFO polyether analogues 2 and 3, beginning with the 3,6,9-trioxadecylation of N-(tert-butoxycarbonyl)-O-benzylhydroxylamine. Polyethers 2 and 3 are neutral molecules, which are somewhat more lipophilic than the parent DFO. Polyether hydroxamate 2 was shown to be nearly 3 times as effective as desferrioxamine at clearing iron in rats.

Animals↗

A comparative evaluation of iron clearance models.

A comparative study of the non-iron-overloaded, bile duct-cannulated rat and of the Cebus monkey as iron-clearance models is presented. The ability of desferrioxamine, desferrithiocin, and a pyridoxal isonicotinoyl hydrazone (PIH) analogue to clear the metal from these two animals is evaluated. Data suggest that although rodents represent a viable first-line animal screen, there is no strict correspondence between the effectiveness of a chelator in rodents and that in primates. Rodent data should be interpreted carefully as it relates to potential human trials. Iron-loading response, the similarity between multiple human and Cebus serum and hematological values, and the ability to easily observe changes in behavioral patterns clearly render the Cebus monkey the best preclinical screen.

Animals↗

Recovery of left ventricular function after myocardial infarction can be predicted immediately after thrombolysis by semiquantitative intracoronary thallium and technetium pyrophosphate scintigraphy.

The accuracy with which intracoronary thallium and technetium pyrophosphate scintigraphy during intracoronary thrombolysis predicts myocardial salvage was studied in 58 patients with acute myocardial infarction by comparing the acute scintigraphic findings with subsequent left ventricular function. Scintigrams obtained before and immediately after thrombolysis were interpreted by three independent observers using a scoring system. Regional wall motion in the infarct area was determined from left ventricular (LV) cine angiograms using the center-line method. Patients with mild hypokinesis (hypokinesis less than or equal to -2 SD from normal) could be distinguished from those with severe hypokinesis (hypokinesis greater than -2 SD) using the prethrombolysis thallium score with an accuracy of 83%. Accuracy using the post-thrombolysis score was 76%. When the post-thrombolysis thallium and technetium pyrophosphate scores were combined, differentiation was possible in 91% of all patients studied, and in 100% of patients with anterior myocardial infarction. Thus, analysis of combined thallium and technetium pyrophosphate scintigraphy accurately predicts recovery of LV function after thrombolysis and may be helpful in deciding whether acute percutaneous transluminal coronary angioplasty or bypass surgery should be performed after thrombolysis.

Cardiac Output↗

Sodium appetite as well as 24-h variations of fluid balance, mean arterial pressure and heart rate in spontaneously hypertensive (SHR) and normotensive (WKY) rats, when on various sodium diets.

Young SHR and WKY rats were compared, first, concerning sodium (Na) appetite during 'rest', mild social stress and ACTH injections, second, concerning the diurnal patterns of water intake, urine output, mean arterial pressure (MAP) and heart rate (HR) while on various Na diets: 0.5 mmol Na(LNa), 5 or 12-13 mmol Na (CNa), 50 (HNa) or 120 mmol Na (vHNa) per 100 g food. Sodium appetite and water intake were about 50% higher in SHR than in WKY (4-4.5 vs 2.5-3 mmol Na per 100 g body wt day-1). It was modestly increased by both social stress and ACTH, and more so in WKY, thereby approaching that in SHR. Concerning the various Na diets and their influences, daytime resting MAP was modestly lowered in LNaSHR and slightly increased in vHNaSHR compared with CNaSHR but largely equal in all WKY groups. Food-water consumption was concentrated to the active night period, but even high Na-water intakes caused no signs of sustained hypervolaemia, because each intake bout was in both SHR and WKY eliminated by urine within 30-40 min. However, particularly the vHNa diet in SHR also increased the frequency of drinking, and each bout caused transient, evidently neurogenic MAP and HR increases which occurred too rapidly to be consequences of blood volume expansion. As a result, the diurnal MAP-HR patterns in SHR varied markedly with the Na diets, in vHNa group resulting in considerably raised average diurnal MAP levels even though resting daytime MAP was here nearly the same as in CNaSHR. These findings illustrate how largely continuous diurnal recordings are needed to judge correctly the relationships between, for example, Na intake, volume equilibrium and MAP. Finally, the relevance of these results in rats for also judging the control of Na balance in man is discussed.

Animals↗

[Risk factors of classical conversion syndrome--psychogenic seizures and paralyses--observations at a neurologic clinic with 172 patients].

Classical hysterical syndromes are not seldom today, either. In report on 172 patients with psychogenic fits (55% of them) or hysterical paralysis (45%) we found females preponderant in 2/3 of the cases. The beginning of symptoms was more frequent at an adolescent stage of 15 to 25 years of age and between 45 and 55. Nearly half the cases had no profession or were unskilled workers of lower strata in society. 80% of all cases have had severe conflicts or social problems in childhood or later in life. Men demonstrated more frequently professional problems: while female patients more often had problems in relationships. Younger patients were in 12% of the cases burdened with perinatal brain damages. 25% of patients with severe conversion reactions had been operated on for gastric or duodenal ulcers. Numerous occasions for symptoms manifestation are described. Long-lasting syndromes we found especially in women and in cases of psychogenic paralysis.

Adolescent↗