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Biomedical subjects

R Shangraw

Publications and source records attributed to R Shangraw.

8 recordsLinked to original sources
PubMed1996

Dichloroacetate reduces plasma lactate levels but does not reduce infarct size in rabbit myocardium.

Dichloroacetate (DCA), an activator of pyruvate dehydrogenase (PDHC), enhances postischemic mechanical recovery of isolated hearts. It is not known whether this is secondary to reduced infarction or preservation of contractile function in viable cardiomyocytes. This study investigated the effect of DCA on myocardial infarct size. Anesthetized open chest rabbits underwent regional coronary occlusion and reperfusion. DCA (300 mg/kg plus 150 mg/kg 1 h later) was administered intravenously either before occlusion (DCA-O; n = 8) or at reperfusion (DCA-R; n = 7). Control rabbits (n = 8) received saline vehicle. Myocardial PDHC activity was measured after administration of 300 mg/kg i.v. DCA in 10 separate rabbits. DCA reduced plasma lactate levels and increased PDHC activity by 76%, from 2.79 +/- .30 mumol/min.g-1 to 4.92 +/- .44 mumol/min.g-1 (p < .005). However, infarct size in DCA-treated animals was not significantly different from Control (60 +/- 5% DCA-O, 57 +/- 6% DCA-R, 58 +/- 7% Control). We conclude that stimulation of pyruvate dehydrogenase does not limit infarct size.

Animals↗
PubMed1996

Dilution potential: a new perspective.

The objective of this work was to develop a method to assess the dilution capacity of direct compression excipients based on a technique previously proposed by Minchom and Armstrong (MA). The technique involves the addition of increasing quantities of a poorly compactible (compressible) material to the excipient and measuring the resultant decrease in the AUC of the tensile strength versus compaction force profiles. The AUC of each mixture is divided by the AUC of the "0% mixture" to obtain MA's "work potential," called "area ratios" in the present study. The applicability of this approach was tested using three excipients differing in their deformation mechanisms: microcrystalline cellulose (Avicel PH 101, 102, 200, 301, 302) representing a plastic material; dibasic calcium phosphate (Cal-Star) representing a brittle material, and anhydrous lactose, which exhibits both brittle and plastic properties. Ascorbic acid or acetaminophen was the poorly compactible challenge material. In the first study, the MA method was found to apply only to Avicel PH 101, since the area ratios for mixtures containing different compositions of acetaminophen with either Cal-Star or anhydrous lactose remain constant until a certain percentage of drug is exceeded, after which a decline starts to be observed. Further work carried out on mixtures of different grades of Avicel with ascorbic acid revealed that MA's approach reflects only the ability of the excipient to handle internal stress induced by the drug and does not take into account the intrinsic ability of the drug-free excipient to form strong compacts. A new index was thus proposed, called the dilution capacity index (DCI), which weights the MA index by the AUC of the drug-free excipient. The results suggest that DCI can be used to compare different grades of microcrystalline cellulose and provide in-house quality control for microcrystalline cellulose suppliers.

Acetaminophen↗
PubMed1979

Biphasic alterations in glucose metabolism by soleus muscle from the burned limb.

Tissue temperature and in vitro glucose metabolism by rat soleus muscle were studied following a 3-second burn on one hind limb in 90 degrees C water. The injury increased the subcutaneous temperature in the calf of the burned limb to 53.4 +/- 0.7 (SE) degrees C and that between soleus muscle and fibula to 49.4 +/- 1.3 degrees C, both temperatures returning to normal at approximately 3 minutes postburn. The injury resulted in biphasic alterations in glucose metabolism by the soleus muscle from the burned limb; glucose uptake and lactate release were depressed at 4 hours but were elevated above control levels at 3 days postburn. The maintenance of an approximate 1:2 ratio of glucose uptake to lactate release suggested that changes in glucose uptake reflected primarily conversion to tricarbon units rather than changes in the rate of glucose oxidation. Since glucose metabolism by soleus muscle from contralateral unburned limb of injured animals did not differ from controls at any of the test times, the changes in the burned limb were not likely the result of systemic alterations in metabolic and endocrine environment. The biphasic alterations did not correlate with the degree of soleus muscle edema. It is concluded that proximity to the burn wound is a new determinant of abnormal glucose utilization by skeletal muscle.

Animals↗
PubMed1975

Stability of stabilized nitroglycerin tablets in typical distribution and administration systems.

A study was undertaken to determine whether or not the present extreme restrictions on the packaging of nitroglycerin tablets are indeed necessary when dispensing the newer stabilized tablets. Baseline tests were conducted on two molded and two compressed sublingual nitroglycerin tablets to determine weight variation, content uniformity, average potency and friability. Stability tests included: (1) use test designed to simulate patient use from a single bottle of 100 tablets over a one-month period; (2) an open plate study wherein tablets were exposed to the atmosphere for 100 days; (3) strip packaging of tablets using foil-foil or foil-cello systems; (4) placement of tablets in medication cups for a seven-day period; (5) repackaging 30-tablet batches in a variety of common prescription containers. All brands of tablets retained potency during normal use when dispensed and stored in their original containers. However, one brand was superior to all others when placed under stress conditions such as open plate exposure. These tablets also retained labeled potency when exposed in a medication cup for a seven-day period, or when repackaged in either foil-foil or foil-cello strips, or when dispensed in a number of ordinary prescription containers. The study indicated that this brand of nitroglycerin tablets might be handled like any other solid dosage form in hospital distribution systems without endangering patient care. However, exceptions to present packaging restrictions must be cleared with the Food and Drug Administration.

Drug Packaging↗