No abstract

To test the hypothesis that acidosis contributes to the insulin resistance of chronic renal failure (CRF) and impairs the action of insulin to decrease protein degradation, eight CRF patients were studied using the combined L-[1-13C]leucine-euglycemic clamp technique before (acid) and after (NaHCO3) 4 wk treatment with NaHCO3 (pH: acid 7.29 +/- 0.01 vs. NaHCO3 7.36 +/- 0.01, P < 0.001). Protein degradation (PD) was estimated sequentially from the kinetics of a primed continuous infusion of L-[1-13C]leucine in the basal state and during a hyperinsulinemic euglycemic clamp. Insulin sensitivity was measured during the clamp. The correction of acidosis significantly increased the glucose infusion rate necessary to maintain euglycemia (acid 6.44 +/- 0.89 vs. bicarbonate 7.38 +/- 0.90 mg.kg-1.min-1, P < 0.01) and significantly decreased PD in the basal state (acid 126.4 +/- 8.1 vs. bicarbonate 100.1 +/- 6.9 mumol.kg-1.h-1, P < 0.001). Hyperinsulinemia decreased PD in both studies (acid basal 126.4 +/- 8.1 vs. clamp 96.5 +/- 7.7, P < 0.001; bicarbonate basal 100.1 +/- 6.9 vs. clamp 88.2 +/- 5.5 mumol.kg-1.h-1, P = 0.06), its effect being unaltered by acidosis, with a reduction of 24% before and 12% after the correction of acidosis. In conclusion, acidosis contributes to the insulin resistance of CRF but does not affect the action of insulin on PD.

Short-term measurements of instantaneous carbon-isotope discrimination have been determined from mass-spectrometric analyses of CO2 collected online during gas exchange for the epiphytic bromeliad Tillandsia utriculata L. Using this technique, the isotopic signature of CO2 exchange for each phase of Crassulacean acid metabolism (CAM) has been characterised. During night-time fixation of CO2 (Phase I), discrimination (Δ) ranged from 4.4 to 6.6‰, equivalent to an effective carbon-isotope ratio (δ(13)C) of -12.3 to -14.5‰ versus Pee Dee Belemnite (PDB). These values reflected the gross photosynthetic balance between net CO2 uptake and refixation of respiratory CO2, characteristic of CAM in the Bromeliaceae. When Δ for the relative proportion of external (p a ) and internal (p i) CO2 is taken into account, calculated p i/p a decreased during the later part of the dark period from 0.68 to 0.48. Measurements of Δ during Phase II, early in the light period, showed the transition between C4 and C3 pathways, with carboxylation being increasingly dominated by ribulose bisphosphate carboxylase (Rubisco) as Δ increased from 10.5 to 21.2‰ During decarboxylation in the light period (Phase III), CO2 leaked out of the leaf and the inherent discrimination of Rubisco was expressed. The value of Δ calculated from on-line measurements (64.4‰) showed that the CO2 lost was considerably enriched in (13)C, and this was confirmed by direct analysis of the CO2 diffusing out into a CO2-free atmosphere (δ (13)C = + 51.6‰ versus PDB). Instantaneous discrimination was characteristic of the C3 pathway during Phase IV (late in the light period), but a reduction in Δ showed an increasing contribution from phosphoenolpyruvate carboxylase. The results from this non-invasive technique confirm the observations that "double carboxylation" involving both phosphoenolpyruvate carboxylase and Rubisco occurs during the transient phases of CAM (II and IV) in the light period.

Cultured human endothelial cells were incubated with high glucose (27.5 mmol/l) supplemented medium for 0, 2, 6, 12, 24 and 48 h. Lactate dehydrogenase was assayed as a measure of cell number. Sorbitol and myoinositol were determined as trimethyl silyl derivatives using gas chromatography mass spectrometry. Sorbitol, after an initial lag phase of 2 h, accumulated rapidly to plateau at 2 to 3 fold control value by 24 h, no further increase being seen over a further 24 h (Baseline, 1.31 +/- 0.36, 24 h 3.50 +/- 0.74 pmol sorbitol/unit lactate dehydrogenase; p less than 0.001). There was no change in myoinositol levels over the 24 h period. Sorbitol accumulation occurred at glucose concentration greater than 18.1 mmol/l and only returned to baseline levels after 24 h of incubation in normal medium (glucose levels 5.9 mmol/l). Sorbitol levels are increased by incubation of endothelial cells at high glucose levels but myoinositol levels remain unchanged.

SummaryA satisfactory clinical response to long-term oral tetracycline treatment was associated with a mean serum tetracycline of 1-98 vg/ml. The surface lipid showed an increased triglyceride, decreased free fatty acids, and decreased cholesterol, and the amount of keratin within the pilosebaceous duct was reduced. At this dose level there was no quantitative decrease in the bacterial flora though there was a decrease in the fatty acids. We believe that the latter was due to a direct inhibition by tetracycline on extracellular lipases.