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L A Bricker

Publications and source records attributed to L A Bricker.

26 records · Page 2Linked to original sources
PubMed1972

In vivo demonstration of the cholesterol feedback system by means of a desmosterol suppression technique.

This report describes a "desmosterol suppression" technique with which it has been possible to demostrate the operation of the cholesterol negative feedback system in the intact animal. 0.1% triparanol in the diet causes a virtually complete block in the conversion of desmosterol to cholesterol by liver and intestine. Since desmosterol is not consumed in the diet, the level of plasma desmosterol can be employed as an index of endogenous sterol production and release into the bloodstream. With this technique it was shown that the feeding of cholesterol for 8 days to rats decreases blood desmosterol levels to less than 5% of control values. Very similar results were obtained when cholesterol synthesis was assayed in vivo with acetate-(14)C as a cholesterol precursor. These observations indicate that the cholesterol feedback system operates very effectively in the intact animal in suppressing the endogenous contribution to the circulating cholesterol pool. Since intestinal cholesterol synthesis is only slightly inhibited by exogenous cholesterol, these results also indicate that the intestine does not represent a significant source of plasma sterols in the rat.

Acetates↗
PubMed1972

Loss of the cholesterol feedback system in the intact hepatoma-bearing rat.

By means of the desmosterol suppression technique described in the previous paper, the influence of hepatomas on sterol metabolism has been studied in the intact rat. The major finding of this study is that all hepatoma-bearing rats demonstrate a consistent in vivo loss of the cholesterol feedback system that is characteristic of normal liver. The results also demonstrate that such tumors retain only minor amounts of the sterol they synthesize, releasing over 90% of such endogenous sterol into the circulation. Finally, the in vivo loss of cholesterol feedback control was found to occur in at least two minimal deviation hepatomas and in one highly malignant adenocarcinoma of hepatic origin. These findings indicate that even tumors that are capable of only very limited cholesterol synthesis in vitro, can contribute significant quantities of sterol to the bloodstream. It is concluded that as a result of their lack of normal cholesterol feedback control, hepatomas may represent a physiologically important source of sterols in the tumor-bearing animal, and that the absence of feedback control of sterol synthesis may provide a means of detecting the presence of such tumors in the intact animal.

Acetates↗
PubMedDate not supplied

Decreased serum cholesterol-binding reserve in diabetes mellitus.

Serum cholesterol-binding reserve (SCBR), the capacity of a serum sample to solubilize additional cholesterol in excess of its cholesterol content, was measured in 43 white male patients with maturity-onset diabetes in the age range of 35--59 years who were under treatment with insulin. The values were compared with those of 194 nondiabetic controls of the same race, sex, and age range. The mean +/- S.D. of SCBR of patients (71.9 +/- 29.3 mg./dl.) was lower than that of controls (88.9 +/- 30.9 mg./dl.) (p less than 0.001). Age in the range of 35 to 59 years had no correlation with SCBR in either patients or controls. SCBR was positively correlated with serum levels of cholesterol (SC) and triglycerides (TG) in both patients and controls. After adjustment for SC and TG, the difference in SCBR between patients and controls persisted (p less than 0.001). In 15 of 20 (75 per cent) patient-control pairs matched for SC and TG to within 5 per cent, the patient had lower SCBR (paired t-test, p less than 0.002). In 16 patients without elevation of serum lipid levels (SC below 250 and TG below 150 mg./dl.), the mean +/- S.D. of SCBR (59.1 +/- 17.7 mg./dl.) was lower than that of 49 controls having serum lipids in the same range (77.4 +/- 31.7 mg./dl.) (p less than 0.03). These results indicate an association of decreased SCBR with diabetes and are consistent with the hypothesis that low SCBR is associated with accelerated atherosclerosis and enhanced risk for coronary heart disease.

Adult↗
PubMedDate not supplied

Intractable diarrhea in hyperthyroidism: management with beta-adrenergic blockade.

OBJECTIVE: To describe a patient with intractable diarrhea and thyrotoxic Graves' disease, for whom b-adrenergic blockade ultimately proved to be effective therapy for the diarrhea, and to review the types of hyperthyroidism-associated diarrhea. METHODS: We present the clinical course of a young man with a prolonged siege of diarrhea that proved elusive to diagnostic inquiries and resistant to all means of management until its endocrine basis was discovered. Control of such cases with b-adrenergic blockade is discussed, as are the pathophysiologic bases of intestinal hypermotility in hyperthyroidism. RESULTS: A 26-year-old man with Down syndrome, and no prior gastrointestinal disorder, had insidious, chronic, constant diarrhea, which was associated with loss of 14 kg during a 5-month period. Numerous laboratory and imaging studies and endoscopic examinations failed to disclose the cause of the diarrhea. Furthermore, a broad range of antibiotics and other empiric remedies failed to control the problem. No other symptoms of hyperthyroidism were reported, but when the endocrinopathy was suspected and identified, the diarrhea was promptly controlled by treatment with propranolol. In patients with hyperthyroidism, two types of diarrheal disorders have been described-secretory diarrhea and steatorrhea; bile acid malabsorption may have a role in either of these settings. CONCLUSION: In addition to its capacity for blocking the peripheral effects of thyroid hormone on the heart and central nervous system, b-adrenergic blockade is effective in slowing intestinal transit time and ameliorating the uncommon diarrhea associated with hyperthyroidism. Thyroid hormone in excess, among its other possible effects on the gastrointestinal tract, may exert a stimulatory effect by means of intermediary sympathetic activation, as it does with the heart. Thus, sympathetic blockade can mimic the salutary effects on the gastrointestinal tract conventionally brought about by direct antithyroid therapy, and well before the hyperthyroid state per se is eliminated. The current patient illustrates the value of considering hyperthyroidism in the differential diagnosis of diarrhea of unknown cause.

Adrenergic beta-Antagonists↗