Stability of heparin in intravenous fluids.
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Drug Stability↗
Biomedical subjects
M R Davis
Publications and source records attributed to M R Davis.
An evaluation of the British Pharmacopoeial assay of heparin: a comparison with other methods.
The potencies of six commercially manufactured heparins have been measured by the British Pharmacopoeial (BP) assay and activated partial thromboplastin time (APTT), protamine sulphate, and anti-Xa assays. The APTT/BP potency ratios were found to vary with the preparation but this was not dependent on the tissue source of heparin. For mucosal heparins, the anti-Xa/BP potency ratios were close to unity, but for heparin of lung origin the anti-Xa potency was approximately one-quarter of the BP potency. Four heparin fractions prepared by column gel chromatography of a commercial heparin were similarly examined by all four assays, and there was a wide divergence between the BP potency estimates and those obtained with the other methods. The degree of divergence was found to depend on the molecular size of the fraction.
Biopharmaceutics↗
Assessment of five quantitative methods for determination of total proteins in urine.
1. We assessed five quantitative methods for the determination of urinary total proteins, three of them with precipitation followed by spectrophotomollowed by spectrophotometry (Tsuchyga/Benedict, Tsuchyga/Biuret and TCA/Biuret); one with gel-filtration (Sephadex G50/Biuret) and a Turbidimetric procedure (SSA). 2. Day-to-day precision was between 3.58 %CV (Tsuchyga/Benedict) and 11.46 %CV (Sephadex/Biuret). The Tsuchyga/Benedict method showed the closest values to controls quantitated by the Kjeldahl method and the lowest detection limit )17.3 mg of total proteins per liter). Recovery studies showed that a level of 100-200 mg/l the Tsuchyga/Benedict recovered over the 96% of the protein added. 3. Comparison studies of 66 24-hour urine samples showed that the best correlation was obtained between the Tsuchyga/Benedict and the Tsuchyga/Biuret methods (r = 0.996). 4. We conclude that the Tsuchyga/Benedict is a sensitive, precise and accurate procedure for the routine quantitation of urinary total proteins.
Biuret Reaction↗
[Clinical evaluation of strip tests for urinary proteins assay (author's transl)].
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Humans↗
Let's put our students on the Pill.
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Contraception↗
In vivo evaluation of the effects of gravitational force (+Gz) on over-the-wire stainless steel Greenfield inferior vena cava filter in swine.
This study was done to determine the effect of exposure to gravitational force (acceleration stress) on in vivo over-the-wire stainless steel Greenfield inferior vena cava filters. Fifteen pigs underwent venous cut down and placement of a stainless steel Greenfield filter. A 4-week observation period simulated realistic convalescence and allowed sufficient time for epithelialization. Ten pigs were exposed to acceleration stress in a centrifuge (3G run for 15 sec followed by rest until return to baseline heart rate, then a 9G run for 15 sec), with inertial loading in a head-to-tail direction (+Gz). Fluoroscopy during acceleration stress allowed assessment for filter migration. Five pigs were not exposed to acceleration stress. AP and lateral abdominal radiographs were obtained at post-filter placement, convalescence, and centrifuge exposure to determine the position and integrity of the filter. All 15 IVCs were resected and evaluated for gross or histological injury to the vessel wall. IVC filter placement was technically successful in all 15 pigs. Radiographic measurements were limited secondary to differences in pig positioning. Fluoroscopy showed no filter migration. All filters were securely attached to the vena cava by the hooks without gross evidence of perforation or hemorrhage. There were varying degrees of fibroplasia involving the hooks and tip of the filters in both the control and experimental groups. Histologically, there was evidence of prior hemorrhage at the level of the hooks, which was similar between the control and experimental groups. It is concluded that Greenfield filter position and vena caval integrity at the implantation site is unaffected by high acceleration stress.
Acceleration↗
Primary hypothyroidism with pituitary hyperplasia and basal ganglia calcifications.
Pituitary enlargement as a result of hypothyroidism is a well recognized entity with several reports over the last decade. Hypothyroidism is only rarely recognized as a cause of basal ganglia calcifications, despite several large computer tomography (CT) studies. We present a case of primary hypothyroidism in which both pituitary hyperplasia and basal ganglia calcifications were observed in a young female who presented with hyperprolactinemia. Hypothyroidism should always be considered in the evaluation of hyperprolactinemia.
Adult↗
Studies on the metabolic fate of caracemide, an experimental antitumor agent, in the rat. Evidence for the release of methyl isocyanate in vivo.
Following administration to rats of a single ip dose (6.6 mg kg-1) of the investigational antitumor agent caracemide (N-acetyl-N,O-bis[methylcarbamoyl]hydroxylamine), the mercapturic acid derivative N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) was identified in urine by thermospray LC-MS. Quantification of this conjugate was carried out by stable isotope dilution thermospray LC-MS, which indicated that the fraction of the caracemide dose recovered as AMCC in 24-h urine collections was 54.0 +/- 5.5% (n = 4). Since AMCC is known to represent a major urinary metabolite of methyl isocyanate (MIC) in the rat, the results of this study support the contention that caracemide yields MIC as a toxic intermediate in vivo. Furthermore, with the aid of a specifically deuterium-labeled analog of caracemide ([carbamoyloxy-C2H3]caracemide), it was shown that the methylcarbamoyl group of AMCC derived from both the O-methylcarbamoyl (72%) and N-methylcarbamoyl (28%) side chains of the drug. In view of these findings, it is concluded that caracemide acts as a latent form of MIC in vivo and that this reactive isocyanate (or labile S-linked conjugates thereof) may contribute to the antitumor properties and/or adverse side-effects of caracemide.
Acetylcysteine↗
Glutathione and N-acetylcysteine conjugates of 2-chloroethyl isocyanate. Identification as metabolites of N,N'-bis(2-chloroethyl)-N-nitrosourea in the rat and inhibitory properties toward glutathione reductase in vitro.
The antitumor agent N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU) is known to be unstable in aqueous solution, and to degrade spontaneously to reactive alkylating and carbamoylating intermediates. Whereas the alkylating component is believed to be responsible for the antitumor effects of this drug, it has been speculated that the carbamoylating species 2-chloroethyl isocyanate (CEIC) may mediate some of the serious adverse effects of BCNU therapy. In order to determine whether CEIC is released from BCNU in vivo, rats were administered an ip injection of the drug and a targeted search was made by ionspray LC-MS/MS techniques for the glutathione (GSH) conjugate of CEIC in bile and for the corresponding N-acetylcysteine (NAC) adduct in urine. Both of these S-linked conjugates were identified on the basis of their HPLC and MS/MS characteristics, which were identical to those of the respective reference compounds prepared by synthesis. Quantitative studies indicated that, following an ip dose of BCNU (24 mg kg-1), excretion of the GSH conjugate in bile over 4 h accounted for 3.90 +/- 0.64% of the administered dose, while excretion of the mercapturic acid derivative in urine over 24 h accounted for a further 18.1 +/- 3.3% (n = 4). Experiments conducted in vitro demonstrated that the S-linked conjugates of CEIC were of limited stability under simulated physiological conditions, decomposing to generate free GSH and NAC. In addition, both adducts inhibited rat liver glutathione reductase in vitro, when they were essentially equipotent to BCNU.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetylcysteine↗
Identification of novel glutathione conjugates of disulfiram and diethyldithiocarbamate in rat bile by liquid chromatography-tandem mass spectrometry. Evidence for metabolic activation of disulfiram in vivo.
Recent studies have shown that the inhibitory effects of disulfiram and diethyldithiocarbamate (DDTC) (to which disulfiram is rapidly reduced in vivo) on the liver mitochondrial low-Km form of aldehyde dehydrogenase (ALDH) may be mediated by a reactive metabolite(s) of these compounds. In order to investigate the nature of such electrophilic intermediates in vivo, the present study was carried out with the goal of detecting and identifying their respective glutathione (GSH) conjugates in the bile of rats dosed ip with either disulfiram (75 mg kg-1) or sodium DDTC (114 mg kg-1). By means of highly selective screening strategies based on coupled liquid chromatography-tandem mass spectrometry techniques, one major and four minor GSH adducts were identified as common biliary metabolites of disulfiram and DDTC. The major conjugate, whose excretion into bile over 4 h accounted for ca. 1% of the dose of either precursor, was identified as S-(N,N-diethylcarbamoyl)glutathione (SDEG). In vitro experiments with synthetic SDEG demonstrated that this carbamate thioester derivative is chemically stable in aqueous media under physiological conditions and does not carbamoylate nucleophiles such as cysteine. Consistent with these findings, SDEG failed to inhibit yeast ALDH in vitro. The minor GSH conjugates in bile were identified as S-(N,N-diethylthiocarbamoyl)glutathione, S-(N-ethyl-carbamoyl)glutathione, S-(N-ethylthiocarbamoyl)glutathione, and S-[N-(carboxymethyl)-N- ethylcarbamoyl]glutathione, the structures of which indicate that metabolic oxidation takes place at the thiono sulfur group and at each of the carbon atoms of disulfiram and DDTC.(ABSTRACT TRUNCATED AT 250 WORDS)
Aldehyde Dehydrogenase↗
Depression and type A behavior pattern in patients with coronary artery disease: relationships to painful versus silent myocardial ischemia and beta-endorphin responses during exercise.
A sample of 45 patients with a history of coronary heart disease and documented myocardial ischemia during exercise testing were evaluated in an investigation of the possible relationships between psychological factors (depression and Type A behavior pattern), plasma beta-endorphin response and pain experience during maximal exercise-induced ischemia. Depression was assessed using the MMPI-D subscale, while Type A was evaluated using the Structured Interview. All patients developed ischemia during exercise as defined by ST-segment depression; however, only 18 patients reported anginal pain. Patients with high depression scores (MMPI-D greater than or equal to 70; n = 13) showed lesser increases in plasma beta-endorphin levels, tended more often to report anginal pain and rated pain as more severe during exercise than patients with low depression scores (MMPI-D less than 60; n = 18). Hemodynamic responses and severity of ischemia (assessed by ejection fraction changes and wall-motion abnormalities) did not differ between depression groups. Even after adjustment for group differences in exercise duration, depression was significantly associated with a lesser beta-endorphin response in the sample as a whole and, among patients reporting angina, with earlier pain onset and greater pain duration and severity. In contrast, when Type A versus B/X subgroups were compared, no differences in pain experience, beta-endorphin response or measures of ischemia were obtained. These findings suggest that in patients with ischemic heart disease, there may be a relationship between depression and anginal pain which may in part involve a blunted or absent beta-endorphin response.
Aged↗
Cardiovascular responses to an active coping challenge as predictors of blood pressure patterns 10 to 15 years later.
To assess the long-term predictive importance of high cardiovascular reactivity in relation to subsequent blood pressure, 51 men from a pool of 204 men originally tested at age 18 to 22 years were recruited for blood pressure assessment 10 to 15 years later. Initial testing uniformly involved monitoring of systolic pressure, diastolic pressure, and heart rate during a reaction time task involving threat of shock. In 30 of the 51 men who participated at follow-up, initial testing had also included separate visits to obtain relaxation-only baseline levels of the cardiovascular indices. At follow-up, in addition to clinic-type stethoscopic determinations, blood pressure and heart rate were assessed during work and social and leisure activities via ambulatory monitoring. Men with higher levels of systolic pressure during the task showed higher stethoscopic and ambulatory systolic pressure at follow-up. Likewise, men with higher levels of diastolic pressure during the task showed higher diastolic levels at follow-up. In the 30 men with both good task and baseline data from initial testing, those with high heart rate reactivity (task minus baseline) showed higher systolic, diastolic, and heart rate levels at follow-up than low heart rate reactors, even though their baseline blood pressures had not differed at initial testing. Similarly, men with high systolic reactivity showed higher diastolic pressure at follow-up than low systolic reactors. Multiple regression analyses also demonstrated that systolic, diastolic, and heart rate reactivity improve prediction of follow-up blood pressure when added to models incorporating the standard risk factors, baseline blood pressure, and parental history of hypertension.
Adaptation, Psychological↗