Toxicity and Teratogenicity Studies with the Hypolipidemic Drug RMI 14,514 in Rats

Toxicity and Teratogenicity Studies with the Hypolipidemic DrugRMI 14,514 in Rats. Gibson, J.P., Larson, E.J.^A, Yarrington,J.T., Hook, R.H., Kariya, T. and Blohm, T.R. (1981 ).Fundam.Appl.Toxicol. 1:19–25. The hypolipidemic drug RMI 14,514 (5-tetradecyloxy-2-furoicacid) has an oral LD50 of over 5000 mg/kg in rats. In a chronictoxicity study (6 months drug diet) doses of 30,100, or 300mg/kg/day produced no obvious signs of toxicity or abnormalclinical pathology parameters, other than prominent growth retardationat 300 mg/ kg, which was somewhat alleviated when the dose wasreduced to 200 mg/kg after 6 weeks. Hepatic change in the formof mild lipid accumulation was noted histopathologically after6 months of treatment at 100 or 300 mg/kg/day, but was not presentat 3 months or after 4 weeks off drug. The administration ofRMI 14,514 in the diet to pregnant rats at 30, 100, or 150 mg/kg/dayon Days 7 thru 21 of pregnancy (day 1 = day sperm detected)did not induce any teratogenic effects. When rats were exposedto the drug from implantation thru sexual maturity (126 daysof age) at the same dosage, it produced no adverse developmentalor behavioral effects, except for slight reduction in weightgain from birth to sexual maturity at 150 mg/kg/day. The drugcaused reductions in plasma cholesterol and total fatty acids,but no distinct changes in various tissue lipids, except inthe erythrocyte where fatty acids and phospholipids were reduced.These differences did not affect membrane integrity of the erythrocyteas far as osmotic or mechanical fragility tests could determine.The drug, which bears a structural resemblance to long-chainfatty acids, was incorporated into tissue lipids in detectableamounts, but tended to disappear from tissues at a rate similarto that of expected lipid turnover after treatment was stopped.     

Effects of eating on plasma hyaluronan in patients with cirrhosis: Its mechanism and influence on clinical interpretation

Circulating levels of hyaluronan (HA) may be a clinically useful non-invasive test in liver disease to evaluate, for example, the degree of fibrosis or cirrhosis. Healthy subjects exhibit a two-fold or greater postprandial elevation of plasma HA. We undertook this work to determine the effect of eating on plasma HA in patients with cirrhosis, to define mechanisms underlying the changes observed and to examine whether using fasting samples improves the discriminating value of plasma HA as a clinical test. Plasma HA was measured using a protein-binding assay in serial samples obtained over 2.5 h, during which a 2100 kJ meal and/or intravenous infusion of octreotide (25 μg stat, 25 μg stat, 25 μg/h) were given, or in paired random and fasting samples from patients with cirrhosis. In six patients with Pugh's A cirrhosis, plasma HA increased more than two-fold after food ingestion, peaking after 75–90 min. In four patients (one Pugh's A), no response was observed. Octreotide transiently increased plasma HA by a mean of 20%, but, in combination with eating, reduced the peak plasma HA by 80% in responding patients. In 30 patients with cirrhosis, random plasma HA was abnormal in only 70% compared with 93% of autologous fasting samples, using the respective normal ranges ( P =0.01). Ingestion of food markedly increased plasma HA in patients with compensated but not decompensated cirrhosis, most likely due to a postprandial increase in splanchnic blood flow. Fasting patients prior to taking blood improves the clinical discriminating value of plasma HA.     

Fatty acid composition of infant formulae1

ABSTRACT. The fatty acid composition of the fats extracted from 27 infant formulae were examined in detail using gas chromatography. The results obtained enabled certain conclusions to be made. These include (1) confirmation that raw cow's milk and unmodified cow's milk preparations are low in essential fatty acids, (2) several of the formulae designed for normal infants contained fatty acids in different proportions to that found in breast milk, and (3) many of the 'special' formulae designed for use when certain specific metabolic or dietary intolerances exist were found to contain either an excess of certain fatty acids considered not beneficial to man such as lauric acid or insufficient essential fatty acid. It is concluded that there is a need for closer scrutiny of the composition of infant formulae.     

OUTPATIENT LUMBAR EPIDURAL CORTICOSTEROID INJECTION IN THE MANAGEMENT OF SCIATICA

The value of epidural injections of corticosteroid as an outpatienttreatment of sciatica has been hitherto uncertain. An epiduralinjection of 80 mg methylprednisolone in 10 ml physiologicalsaline was compared with an interspinous injection of 2 ml physiologicalsaline in a double blind fashion amongst 39 outpatients. Significantdifferences of pain relief were seen between the two groupswithin 2 weeks. This benefit disappeared for six (35%) patientswithin 6 months of treatment although 11 (65%) successfullytreated subjects had sustained improvement up to this time.Outpatient epidural injections of corticosteroid are thus auseful short-term means of relieving pain in sciatica but probablyhave little effect on the long-term natural history of symptoms.Factors associated with a failure to respond to epidural steroidinjections are discussed. KEY WORDS: Nerve root, Disc prolapse, Methylprednisolone, Pain relief ^* Present address: Department of Rheumatology, St Thomas' Hospital,London, SE1.