The effect of sodium deoxycholate and other surfactants on the mucosal surface pH in proximal jejunum or rat

The mucosal surface pH (acid microclimate) and nucleotide levels of rat proximal jejunum were measured in vivo under various conditions which included exposure to pharmacological agents and to surfactants. Mucosal surface pH was unaffected by sodium nitroprusside, A23187 and amiloride, as was mucosal cGMP content, although amiloride and A23187 reduced cAMP content. In contrast, surfactants elevated the pH of the mucosal surface significantly (P < 0.001): control value 6.23 ± 0.02 (n = 12); Lubrol PX 0.8% (v/v) 6.98 ± 0.02 (n = 5); sodium deoxycholate 2 mmol/l 6.67 ± 0.04 (n = 5); Triton X-100 0.5% (v/v) 7.41 ± 0.03 (n = 5). No significant changes in cGMP levels were noted after surfactant treatment, although DOC and Triton X-100 reduced cAMP levels. The ability of higher concentrations of surfactant to elevate the mucosal surface pH beyond neutrality to values similar to plasma pH contrasts with the action of Escherichia coli heat-stable (STa) enterotoxin which at high concentrations could not elevate the mucosal surface pH beyond neutrality. Consistent with the known effects on tight junction permeability, surfactants may act by allowing plasma-like subepithelial fluid to neutralise the microclimate

Mechanical aspects of rabbit fecal dehydration

The hydrostatic pressure required to reduce the water content of rabbit feces in an odometer from greater than 80 to less than 65% was approximately 5 atm. This pressure was unaffected by raising the temperature from 20 to 37 degrees C. It became progressively more difficult to dehydrate feces as consolidation occurred, as is evident from the significant (P less than 0.001) reduction in the fecal consolidation coefficient (Co) from 1.76 +/- 0.25 X 10(-6) (n = 4) to 1.35 +/- 0.093 X 10(-7) m2/s (n = 4) and the fecal fluid permeability coefficient (k) from 4.10 +/- 0.51 X 10(-8) (n = 4) to 1.42 +/- 0.12 X 10(-10) m/s (n = 4), concomitant with the reduction in fecal water content. The results suggest that rabbit hard feces are unlikely to be produced, under physiological conditions, by mechanical pressure exerted by the wall of the colon or by a prolonged retention time of hard feces by the distal colon. The hypertonic absorbate (1,000 mosmol/kg) produced by rabbit descending colon is of sufficient magnitude to overcome the fecal resistance to dehydration. <br/

A novel association between a SNP in CYBRD1 and serum ferritin levels in a cohort study of HFE hereditary haemochromatosis

There is emerging evidence that there are genetic modifiers of iron indices for HFE gene mutation carriers at risk of hereditary hemochromatosis. A random sample, stratified by HFE genotype, of 863 from a cohort of 31 192 people of northern European descent provided blood samples for genotyping of 476 single nucleotide polymorphisms (SNPs) in 44 genes involved in iron metabolism. Single SNP association testing, using linear regression models adjusted for sex, menopause and HFE genotype, was conducted for four continuously distributed outcomes: serum ferritin (log transformed), transferrin saturation, serum transferrin, and serum iron. The SNP rs884409 in CYBRD1 is a novel modifier specific to HFE C282Y homozygotes. Median unadjusted serum ferritin concentration decreased from 1194 microg/l (N = 27) to 387 microg/l (N = 16) for male C282Y homozygotes and from 357 microg/l (N = 42) to 69 microg/l (N = 12) for females, comparing those with no copies to those with one copy of rs884409. Functional testing of this CYBRD1 promoter polymorphism using a heterologous expression assay resulted in a 30% decrease in basal promoter activity relative to the common genotype (P = 0.004). This putative genetic modifier of iron overload expression accounts for 11% (95% CI 0.4%, 22.6%) of the variance in serum ferritin levels of C282Y homozygotes