Heme biosynthesis in a chicken hepatoma cell line (LMH): comparison with primary chick embryo liver cells (CELC).
5-Aminolevulinic acid synthase (ALA synthase), the rate-controlling enzyme of hepatic heme biosynthesis, is feed-back repressed by heme. In the liver, chemicals such as barbiturates markedly induce ALA synthase, especially in the presence of partial defects of heme biosynthesis. The inducibility and regulation of ALA synthase have been investigated using a variety of models, including intact animals and liver cell culture systems. A widely used model that closely approximates what occurs in vivo and in humans is that of primary cultures of chick embryo liver cells (CELCs). However, CELCs have some limitations: the cells obtained are somewhat heterogeneous; isolation and culture must be repeated every week resulting in weekly variations; and cells are short-lived limiting the feasibility of time-course and transfection studies. The aim of this study was to determine if LMH cells, a chick hepatoma cell line, are a good model comparable to that of CELCs. In both cells similar patterns of response of, ALA synthase activities and mRNA levels, and of porphyrin accumulation were obtained following treatments known to affect heme biosynthesis. Similarly, heme repressed ALA synthase mRNA levels in both cell types and ALA synthase activities in LMH cells. We conclude that LMH cells are a useful model for the study of hepatic heme biosynthesis and regulation of ALA synthase. (+info)
Use of charcoal haemoperfusion in the management of severely poisoned patients.
The clinical use of uncoated charcoal haemoperfusion systems, despite their efficacy, has hitherto been prevented by the occurrence of a number of adverse effects including charcoal embolism and marked thrombocytopenia. Charcoal coated with a synthetic hydrogel overcomes many of the disadvantages associated with the use of uncoated material in that there is a much reduced thrombocytopenia and no evidence of charcoal embolism. Six patients, severely poisoned as a result of overdoses of either a barbiturate or glutethimide, were haemoperfused using such a system. Four made complete recoveries, and the two patients who died had both suffered cardiorespiratory arrests before perfusion. In contrast to haemodialysis charcoal haemoperfusion is simple to initiate, less expensive in terms of manpower and equipment, and gives superior clearance data for all barbiturates and glutethimide. We believe that this technique may have a significant role to play in the management of the severely poisoned patient. (+info)
Applications of a Vidicon spectrometer to analytical problems in clinical chemistry.
This report discusses characteristics of a custom-designed vidicon spectrometer and evaluates its applicability to several clinical analysis problems. Data show that the vidicon detector response is linear with intensity over about four orders of magnitude and that the uncertainty in absorbance measurements can approach 0.001 absorbance units in the range from 0 to 2 absorbance units. Applications include the enzymatic determination of glucose, the determination of lactate dehydrogenase, and determinations of barbital, chlordiazepoxide, and glutethimide. Capabilities of the instrument system for first-derivative spectroscopy are also discussed. The discussion included a critical evaluation of the potential advantages and limitations of the concept. (+info)
Comparative clinical study of two hypnotic drugs.
The comparative sleep-inducing and sleep-sustaining effects of glutethimide, 0.5 g., and ethchlorvynol, 0.5 g., were studied in 20 patients hospitalized for a considerable time (average: 21 years; minimum nine years and maximum 32 years) and not receiving psychotropic agents. Assessment of sleep and para-sleep parameters (pre-sleep tension; frequency of awakening at night; post-sleep activity) revealed that patients fell asleep faster (P>.001) and slept for a longer time with ethchlorvynol than with glutethimide. (+info)
Clinical and statistical evaluation of six hypnotic agents.
Six hypnotic drugs and a placebo were coded and administered at random, one dose at 8 p.m., to 20 patients in a Toronto hospital. A special evaluation scale was used, studying average duration of sleep, time of onset of sleep, quality of sleep and side effects. Secobarbital sodium and methyprylon were statistically significantly more effective than the placebo. The other drugs, glutethimide and three quinozolinone derivatives, were not statistically different from the placebo in their effects. The placebo effect itself was studied. A particular feature of this report is the detailed statistical treatment of the data collected. (+info)
KORSAKOFF'S SYNDROME ASSOCIATED WITH ADRENAL VIRILISM.
Korsakoff's syndrome of obscure etiology was observed in a 34-year-old single woman with an 11-year history of hirsutism and mood swings, and previous hospitalizations for mania three years ago and depression 11 years ago.Recently the virilism had intensified with increased muscularity and coarsening of facial features. The 24-hour urinary 17-ketosteroids ranged between 14.4 mg. and 21.5 mg. and were suppressed by dexamethasone. The 17-hydroxycorticosteroid excretion was normal. These and other findings suggested a diagnosis of adrenal virilism due to adrenocortical hyperplasia. In the absence of other discernible causes it appeared that the adrenal pathology was responsible for the Korsakoff's syndrome. Both conditions responded well to glucocorticoid therapy although low doses were necessary to avoid mania.It is speculated that the encephalopathy was due to an associated adrenal insufficiency. Although hypoadrenalism is accepted as a complication of only the infant form of adrenal virilism, it is noteworthy that this patient had pathological pigmentation of her skin. (+info)
A CLINICAL EVALUATION OF FOUR HYPNOTIC AGENTS, USING A LATIN-SQUARE DESIGN.
A double-blind study with a Latin-square design was undertaken on 25 elderly patients, using a placebo and four hypnotic drugs: ethchlorvynol 500 mg., glutethimide 500 mg., chloral hydrate 500 mg., and secobarbital sodium 100 mg. The trial lasted for five weeks. The drugs were all effective compared with the placebo, differences in sleeping time being statistically significant. Differences between these four drugs were not statistically significant. Sleep was induced soonest by secobarbital and ethchlorvynol. Ethchlorvynol and glutethimide had a relatively somewhat longer period of activity than the others. Glutethimide produced most side effects, especially morning drowsiness. Ethchlorvynol and chloral hydrate produced relatively few cases of drowsiness. (+info)
Haem repression of the housekeeping 5-aminolaevulinic acid synthase gene in the hepatoma cell line LMH.
Haem is essential for the health and function of nearly all cells. 5-Aminolaevulinic acid synthase-1 (ALAS-1) catalyses the first and rate-controlling step of haem biosynthesis. ALAS-1 is repressed by haem and is induced strongly by lipophilic drugs that also induce CYP (cytochrome P450) proteins. We investigated the effects on the avian ALAS-1 gene promoter of a phenobarbital-like chemical, Glut (glutethimide), and a haem synthesis inhibitor, DHA (4,6-dioxoheptanoic acid), using a reporter gene assay in transiently transfected LMH (Leghorn male hepatoma) hepatoma cells. A 9.1 kb cALAS-1 (chicken ALAS-1) promoter-luciferase-reporter construct, was poorly induced by Glut and not by DHA alone, but was synergistically induced by the combination. In contrast, a 3.5 kb promoter ALAS-1 construct was induced by Glut alone, without any further effect of DHA. In addition, exogenous haem (20 microM) repressed the basal and Glut- and DHA-induced activity of luciferase reporter constructs containing 9.1 and 6.3 kb of ALAS-1 5'-flanking region but not the construct containing the first 3.5 kb of promoter sequence. This effect of haem was subsequently shown to be dependent on the -6.3 to -3.5 kb region of the 5'-flanking region of cALAS-1 and requires the native orientation of the region. Two deletion constructs of this approx. 2.8 kb haem-repressive region (1.7 and 1.1 kb constructs) retained haem-dependent repression of basal and drug inductions, suggesting that more than one cis-acting elements are responsible for this haem-dependent repression of ALAS-1. These results demonstrate that there are regulatory regions in the 5'-flanking region of the cALAS-1 gene that respond to haem and provide a basis for further investigations of the molecular mechanisms by which haem down-regulates expression of the ALAS-1 gene. (+info)