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Biomedical subjects

S Barnes

Publications and source records attributed to S Barnes.

At least 235 records · Page 13Linked to original sources

Evidence for renal control of urinary excretion of bile acids and bile acid sulphates in the cholestatic syndrome.

1. The bile acids and bile acid sulphates in the urine, serum and bile of eight cholestatic patients were studied quantitatively by gasliquid chromatography and gas-liquid chromoatography/mass spectrometry. 2. The primary bile acids (cholic acid and chenodeoxycholic acid) comprised on average 94% of the total bile acids in bile, 70% in the serum and 64% in urine. 3. The percentage composition of bile acids in bile was relatively constant and was not influenced by the degree of cholestasis. In contrast, in the serum only the primary bile acids were increased, the concentrations of the secondary bile acids (deoxycholic acid and lithocholic acid) and the minor bile acids remaining constant. 4. The data do not support the hypothesis that monohydroxy bile acids accumulate in cholestasis and are related to the pathogenesis of this syndrome. 5. The pattern of bile acid urinary excretion was similar to that in the serum. But in one patient, 3alpha, 7beta, 12alpha-trihydroxy-5beta-cholan-24-oic acid was a principal urinary bile acid, although very low concentrations of the compound were found in that patient's serum, suggesting that some of the minor bile acids in urine may originate by epimerization in the kidney. 6. In bile only a small proportion of the bile acids was sulphated (range 2.1-4.6%) and in serum the degree of sulphation was very variable (9-50%). However, in urine, sulphate esters accounted for a large proportion of the total bile acids (33-72%). 7. The output of bile acid sulphate in the urine was related to the urine total bile acid output but the serum concentration of bile acid sulphate remained relatively constant. Consequently, in contrast to the non-sulphated bile acids, whose renal clearance was relatively constant, the renal clearance of sulphated bile acids was directly related to the urine total bile acid output. This finding is inconsistent with the earlier hypothesis that their predominance in urine was due to a high renal clearance. It may indicate renal synthesis of some of the bile acid sulphates in the urine and/or inhibition of active renal tubular reabsorption of sulphated bile acids by non-sulphated bile acids.

Adult↗

Assessment of the plasma disappearance of cholyl'l14C-glycine as a test of hepatocellular disease.

The plasma disappearance of a tracer dose of cholyl-l14C-glycine has been examined in 12 control subjects and in 32 patients with hepatocellular dysfunction. Simple analysis of the data did not detect hepatic dysfunction except in severe hepatocellular disease. The greatest degree of discrimination between normal subjects and patients with mild liver disease was obtained by taking the ratio of the plasma retention at 60 minutes to that at 10 minutes; it was similar to that obtained with serum gamma-glutamyl transferase. The two hour post-prandial plasma "total" bile acid concentration gave complete separation between the control subjects and patients with liver disease.

Adult↗

Bile acids in liver disease associated with inflammatory bowel disease.

To investigate the possibility that bowel-related liver disease is due to accumulation of abnormal bile acids in the enterohepatic circulation, bile acids have been measured in gall-bladder bile and portal blood of patients with chronic bowel disease, none of whom had liver disease. There was no difference in the composition and concentration of bile acids in bile and portal blood compared with control patients. In a second study, serum bile acid composition and concentrations were similar in two groups of patients with liver disease, whether they had bowel disease or not. In a further study, post-prandial serum bile acid concentrations were not elevated in a group of patients with chronic bowel disease, making it unlikely that subcliical liver disease was present. No evidence has been found to support the hypothesis that bowel-related liver disease in man results from the action of abnormal bile acids.

Adult↗

A simplified procedure for the isolation of bile acids from serum based on a batch extraction with the non-ionic resin--Amberlite XAD-7.

A simple and reproducible method using the non-ionic resin, Amberlite XAD-7, for the isolation of bile acids from serum by a batch procedure is described. Recoveries were greater than 95% for the non-sulphated bile acids and greater than 70% for the sulphate esters of bile acids. By using 1 g of resin, recoveries were independent of the mass (0.1-5 mumol) of the bile acid present. Up to 35 samples a day can be extracted without requiring dedication of the operator. When serum extracts were analysed by the 3alpha-hydroxysteroid dehydrogenase procedure for estimation of bile acids, virtually all the background fluorescence was eliminated. These extracts were also suitable for gas liquid chromatography, thin layer chromatography, and radioimmunoassay.

Bile Acids and Salts↗

Diagnositic value of serum bile acid estimations in liver disease.

Bile acid concentrations were estimated enzymatically in fasting and postprandial (two-hour) serum samples from 18 normal subjects and 30 patients with histologically proven hepatobiliary disease. The serum bile acid concentration was less than 15 mumol/1 in normal subjects and did not increase postprandially. The fasting serum bile acid concentration was raised in 27 of the patients with hepatobiliary disease, and following a meal was outside the normal range in all 30 patients. Other liver function tests were abnormal less frequently. These results suggest that the estimation of serum bile acids in the postprandial state is a sensitive screening test of hepatobiliary disease. They should be of particular value in patients in whom liver disease is suspected but not proven, and in those recovering from liver disease, especially following therapy.

Adolescent↗

Abortion.

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Abortion, Legal↗

Bile salt micelles: nuclear magnetic resonance spectroscopy and crystallographic studies.

Studies of bile salt structure using nuclear magnetic resonance (NMR) and X-ray crystallography have suggested that micellar association of bile salts is a function of side chain length and of packing of the side chain and the steroid nucleus. Lanthanide NMR probe analysis has been used to determine the structure of what is probably the monomer of the bile salt glycocholate. These approaches to the structural chemistry of bile salt intra- and intermolecular interactions are providing the basis for the design of artificial bile salt-like compounds for use in the study and treatment of human gallstone disease.

Bile Acids and Salts↗

The pediatric cardiology pharmacopoeia: 2004 update.

Seven years ago, Pediatric Cardiology published the first version of a review article outlining the various medications used in the field of heart diseases in children. This article is an update and expansion to what we have previously presented. Therapeutic intervention, both surgical and through cardiac catheterization, has enabled cure and palliation of an increasingly expanding spectrum of diseases at earlier ages and with more complex lesions. Refinement of these procedures includes more advanced tools as well as the support of an expanding armament of pharmacopoeia used to stabilize and support patients before, during, and after such procedures. In addition to updating previously published data regarding inotropes, antiarrhythmics, vasodilators, diuretics, sedatives, and analgesics as well as a variety of miscellaneous medications, this article describes the use of pulmonary medications frequently needed in patients with congestive heart failure, pulmonary edema, and chronic lung disease. We also describe the difficult management of withdrawal as a result of use of sedatives and analgesics. The most recent recommendation for subacute bacterial endocarditis prophylactic antibiotic regimens is also described.

Cardiology↗

The chemopreventive properties of soy isoflavonoids in animal models of breast cancer.

Genistein (5,7,4'-trihydroxyisoflavone), one of two major isoflavonoids in soy, has anti-proliferative effects on mitogen-stimulated cell growth of human breast cancer cells in culture and is a candidate for use in the prevention of breast cancer. Soy protein preparations containing isoflavonoid conjugates have chemopreventive activity in carcinogen-induced rat models of breast cancer. Recent experiments in these models with purified genistein have revealed that the timing of the exposure of rats to this isoflavonoid is critical. Rats treated neonatally or prepuberally with genistein have a longer latency before the appearance of 7,12-dimethylbenz[a]anthracene-induced mammary tumors and a marked reduction in tumor number. The mechanism of genistein's preventive action is in part dependent on its estrogenic activity, which causes a more rapid differentiation of the cells of the mammary gland, and analogous to the effects of an early pregnancy. Rats administered genistein after 35 days of age have smaller alterations in breast cancer risk, with a maximum reduction in mammary tumor number of 27%. In ovariectomized nude mice, dietary genistein increases cell proliferation of human breast cancer MCF-7 cell xenografts compared with a control diet. This estrogen-like effect of genistein is not observed in non-ovariectomized rats. Future studies on the anticancer potential of soy isoflavonoids should examine their interaction with other phytochemical components of soybeans and exploit newly developed animal models of breast cancer in which specific genes have been activated or inactivated.

Animals↗

Cyclic-nucleotide-gated channels mediate synaptic feedback by nitric oxide.

Cyclic-nucleotide-gated (CNG) channels in outer segments of vertebrate photoreceptors generate electrical signals in response to changes in cyclic GMP concentration during phototransduction. CNG channels also allow the influx of Ca2+, which is essential for photoreceptor adaptation. In cone photoreceptors, cGMP triggers an increase in membrane capacitance indicative of exocytosis, suggesting that CNG channels are also involved in synaptic function. Here we examine whether CNG channels reside in cone terminals and whether they regulate neurotransmitter release, specifically in response to nitric oxide (NO), a retrograde transmitter that increases cGMP synthesis and potentiates synaptic transmission in the brain. Using intact retina, we show that endogenous NO modulates synapses between cones and horizontal cells. In experiments on isolated cones, we show directly that CNG channels occur in clusters and are indirectly activated by S-nitrosocysteine (SNC), an NO donor. Furthermore, both SNC and pCPT-cGMP, a membrane-permeant analogue of cGMP, trigger the release of transmitter from the cone terminals. The NO-induced transmitter release is suppressed by guanylate cyclase inhibitors and prevented by direct activation of CNG channels, indicating that their activation is required for NO to elicit release. These results expand our view of CNG channel function to include the regulation of synaptic transmission and mediation of the presynaptic effects of NO.

Ambystoma↗