Do colonic bacteria contribute to cholesterol gall-stone formation? Effects of lactulose on bile.

Ten healthy middle-aged women volunteered for a study to test the effect of lactulose--a synthetic, non-absorbable disaccharide--on the colonic metabolism of bile acids and on bile lipid composition. Lactulose (60 g daily in eight cases, 39 g daily in two) was taken as a proprietary syrup for six weeks, and bile was collected by duodenal intubation before and immediately after six weeks. All subjects showed a fall in the percentage of the 7-alpha-dehydroxylated bile acid deoxycholic acid (mean 28.4 +/- SEM 3.7 to 15.6 +/- 2.4; p less than 0.002) and a rise in the percentage of the primary bile acid chenodeoxycholic acid (mean 33.2 +/- 42.9 +/- 2.9; p less than 0.001). The percentage of cholic acid rose in eight subjects but mean values did not differ significantly. Bile was initially super-saturated with cholesterol in most subjects and became less saturated with cholesterol in all but one (mean saturation index 1.40 +/- 0.11 to 1.19 +/- 0.07; p less these 0.005). These data support the theory colonic bacteria contribute to cholesterol gall-stone formation.     

Growth-induced mass flows in fungal networks

Cord-forming fungi form extensive networks that continuously adapt to maintain an efficient transport system. As osmotically driven water uptake is often distal from the tips, and aqueous fluids are incompressible, we propose that growth induces mass flows across the mycelium, whether or not there are intrahyphal concentration gradients. We imaged the temporal evolution of networks formed by Phanerochaete velutina, and at each stage calculated the unique set of currents that account for the observed changes in cord volume, while minimizing the work required to overcome viscous drag. Predicted speeds were in reasonable agreement with experimental data, and the pressure gradients needed to produce these flows are small. Furthermore, cords that were predicted to carry fast-moving or large currents were significantly more likely to increase in size than cords with slow-moving or small currents. The incompressibility of the fluids within fungi means there is a rapid global response to local fluid movements. Hence velocity of fluid flow is a local signal that conveys quasi-global information about the role of a cord within the mycelium. We suggest that fluid incompressibility and the coupling of growth and mass flow are critical physical features that enable the development of efficient, adaptive biological transport networks.     

Pycnogenol® and vitamin E inhibit ethanol‐induced apoptosis in rat cerebellar granule cells

Pycnogenol® (PYC), a patented combination of bioflavonoids extracted from the bark of French maritime pine (Pinus maritima), scavenges free radicals and promotes cellular health. The protective capacity of PYC against ethanol toxicity of neurons has not previously been explored. The present study demonstrates that in postnatal day 9 (P9) rat cerebellar granule cells the antioxidants vitamin E (VE) and PYC (1) dose dependently block cell death following 400, 800, and 1600 mg/dL ethanol exposure (2) inhibit the ethanol‐induced activation of caspase‐3 in the same model system; and (3) reduce neuronal membrane disruption as assayed by phosphatidylserine translocation to the cell surface. These results suggest that both PYC and VE have the potential to act as therapeutic agents, antagonizing the induction of neuronal cell death by ethanol exposure. © 2004 Wiley Periodicals, Inc. J Neurobiol 59: 261–271, 2004     

Alcohol consumption and its relation to cardiovascular risk factors in British women.

OBJECTIVE--To examine the relation between alcohol consumption and risk factors for coronary heart disease in women. DESIGN--Cross sectional study of a stratified random sample of the population grouped into five categories of habitual alcohol consumption. SETTING--People registered with general practitioners at two large health centres in east Bristol, England. SUBJECTS--1048 women aged 25-69 years. MAIN OUTCOME MEASURES--Fasting plasma concentrations of insulin, total cholesterol, total triglycerides, and high density lipoprotein cholesterol, including its subfractions HDL2 and HDL3, and body mass index. RESULTS--Compared with non-drinkers women consuming a moderate amount of alcohol (1-20 g/day) had lower plasma concentrations of triglycerides, by 0.19 mmol/l (95% confidence interval 0.07 to 0.35); cholesterol, by 0.4 mmol/l (0.19 to 0.61); and insulin, by 1.4 mU/l (0.43 to 1.97) and a lower body mass index, by 1.2 kg/m2 (0.43 to 1.97). They also had higher concentrations of high density lipoprotein cholesterol, by 0.09 mmol/l (0.03 to 0.15); HDL2 cholesterol by 0.05 mmol/l (-0.02 to 0.10) and HDL3 cholesterol, by 0.06 mmol/l (0.06 to 0.11). All these were independent of body mass index, smoking habits, and taking oral contraceptives. CONCLUSIONS--Moderate alcohol consumption is associated with lower levels of cardiovascular risk factors in women. Insulin may have a central role.     

Sugar,fat, and the risk of colorectal cancer.

The habitual diet of 50 patients with large bowel cancer, as assessed by a dietary history method, was compared with that of 50 closely matched controls. Patients were included only if their symptoms were unlikely to have changed previous eating habits. The mean daily intakes of all major nutrient classes and of dietary fibre were estimated. Patients with large bowel cancer consumed 16% more energy than controls (mean (SEM) daily intake 9.92 (0.41) v 8.56 (0.32) MJ (2370 (98) v 2046 (76) kcal), respectively; p less than 0.0001), mainly in the form of carbohydrate (21% more; 282.6 (13.7) v 233.4 (10.5) g; p less than 0.0001) and fat (14% more; 100.8 (4.3) v 88.4 (3.2) g; p less than 0.001). The extra carbohydrate was largely in the form of sugars depleted in fibre and the extra fat as combinations of fat and such sugars. As the selection criteria used make it unlikely that this eating pattern was caused by the disease the data suggest that a high intake of sugars depleted in fibre and fat predisposes to the development of large bowel cancer.     

Insulin regulation of insulin-like growth factor action in rat hepatoma cells

We have reported previously that insulin causes a complete but reversible desensitization to insulin action in rat hepatoma HTC cells in tissue culture, and that this insulin resistance is mediated by postbinding mechanisms rather than receptor down-regulation (Heaton, J. H., and Gelehrter, T. D. (1981) J. Biol. Chem. 256, 12257-12262). We report here that insulin causes a similar desensitization to the induction of tyrosine aminotransferase by the insulin-like growth factors IGF-I and IGF-II isolated from human plasma, and by multiplication-stimulating activity, the rat homologue of IGF-II. The results of both competition-binding studies and affinity cross-linking experiments indicate that insulin-like growth factors (IGFs) bind primarily to IGF receptors rather than to insulin receptors. The low concentrations at which these factors induce transaminase is consistent with their acting primarily via IGF receptors. This is confirmed by experiments utilizing anti-insulin receptor antibody which both inhibits 125I-insulin binding and shifts the concentration dependence of insulin induction of tyrosine aminotransferase to the right. This same immunoglobulin does not inhibit 125I-multiplication-stimulating activity binding and only minimally inhibits 125I-IGF-I binding. Anti-insulin receptor antibody also does not significantly shift the concentration dependence for the IGFs, suggesting that IGFs induce transaminase by acting via IGF receptors. Although insulin down regulates insulin receptors, it does not decrease IGF-I or IGF-II binding. We conclude that insulin causes desensitization of HTC cells to IGFs by affecting a postbinding step in IGF action, which may be common to the actions of both insulin and insulin-like growth factors.     

Patients' and general practitioners' satisfaction with information given on discharge from hospital: audit of a new information card.

OBJECTIVE--To determine the attitudes of patients discharged from hospital and their general practitioners to a new information card giving details about admission, diagnosis, and treatment and to assess the completeness of the information on the card. DESIGN--Consecutive patients discharged from the care of three consultant physicians over 16 weeks. SETTING--One general medical ward in a large teaching hospital. PATIENTS--A total of 275 consecutive discharges of 258 patients were studied. The mean age of patients was 60 years and mean duration of admission five days. INTERVENTION--At discharge from the ward all study patients received an information card and a copy of the card in the form of an interim discharge letter to be delivered to their general practitioner. Patients and general practitioners were asked to complete a questionnaire giving their views on the legibility, helpfulness, quality, and quantity of the information they received. Copies of all the information cards were scrutinised for completeness. MAIN RESULTS--The results were based on 208 (76%) forms returned by patients and 214 (78%) forms returned by general practitioners. Information was considered very helpful or quite helpful according to 170 (83%) forms from patients and 197 (92%) forms from general practitioners; sufficient information was provided according to 160 and 182 forms. Most patients and nearly all general practitioners thought it was a good idea to provide this information for patients at discharge. According to 125 forms from patients and 188 from general practitioners the information card was very easy or quite easy to read; 155 patients had read it at least twice and 149 were likely to refer to it again. OTHER RESULTS--The written information about the patient, the diagnosis, and what the patient had been told was generally well completed, although the date of discharge was omitted from 42 (15%) cards. Details of drugs prescribed at discharge were generally thorough. CONCLUSIONS--Giving an information card to all patients at discharge was feasible and favoured by most patients and their general practitioners. Having made minor changes in design, we think that we have produced an information card that is a convenient size and will improve communication between patients, their general practitioners, and hospital doctors. We now issue this card routinely to all patients discharged from our ward and hope that it might be widely adopted.     

Structure and assembly of turnip crinkle virus. VI. Identification of coat protein binding sites on the RNA

Structural studies of turnip crinkle virus have been extended to include the identification of high-affinity coat protein binding sites on the RNA genome. Virus was dissociated at elevated pH and ionic strength, and a ribonucleoprotein complex (rp-complex) was isolated by chromatography on Sephacryl S-200. Genomic RNA fragments in the rp-complex, resistant to RNase A and RNase T1 digestion and associated with tightly bound coat protein subunits, were isolated using coat-protein-specific antibodies. The identity of the protected fragments was determined by direct RNA sequencing. These approaches allowed us to study the specific RNA-protein interactions in the rp-complex obtained from dissociated virus particles. The location of one protected fragment downstream from the amber terminator codon in the first and largest of the three viral open reading frames suggests that the coat protein may play a role in the regulation of the expression of the polymerase gene. We have also identified an additional cluster of T1-protected fragments in the region of the coat protein gene that may represent further high-affinity sites involved in assembly recognition.