Background : 5‐aminosalicylic acid (5‐ASA) has been associated with renal complications in inflammatory bowel disease. Renal function is typically monitored using serum creatinine; however, significant disease may predate increases in creatinine. Aims : To identify whether markers of early renal disease (urinary albumin, α‐1‐microglobulin [α‐1‐M] and N‐acetyl‐β‐D‐glucosaminidase [NAG], and serum cystatin C) are useful in the assessment of renal function in inflammatory bowel disease patients receiving 5‐ASA. Methods : Twenty‐one patients with a new diagnosis of inflammatory bowel disease were investigated. Samples were taken at diagnosis, and at 3‐monthly intervals after the commencement of 5‐ASA, for 1 year. Results : Mean creatinine clearance was 100 mL/min and did not change following treatment. Inflammatory bowel disease was not associated with albuminuria. Urinary N‐acetyl‐β‐D‐glucosaminidase and α‐1‐microglobulin at diagnosis were increased in 10 (48%) and 11 (52%) patients, respectively: treatment was not associated with consistent changes in urinary protein excretion. There was a significant correlation between cystatin C and creatinine clearance both at diagnosis (r=–0.533, P=0.0275) and combining the initial and follow‐up data (r=–0.601, P < 0.01), but not between creatinine and creatinine clearance (P > 0.05). Conclusions : Tubular proteinuria is an extra‐intestinal manifestation of inflammatory bowel disease irrespective of 5‐ASA treatment. Tubular proteins are not useful predictors of an adverse renal response to 5‐ASA. Serum cystatin C may be an improved marker of glomerular filtration rate in this setting.

SUMMARYAim: To establish whether bone disease is present at diagnosis in inflammatory bowel disease and to identify contributory metabolic abnormalities. Methods: Newly diagnosed patients with inflammatory bowel disease (19 males, 15 females; mean age, 44 years; range, 17-79 years; 23 ulcerative colitis, 11 Crohn's disease) were compared against standard reference ranges and a control group with irritable bowel syndrome (eight males, 10 females; mean age, 40 years; range, 19-64 years). Bone mineral density (g ⁄ cm 2 , dual-energy X-ray absorptiometry: lumbar spine and femoral neck) and biochemical bone markers were measured. Results: Femoral neck bone mineral density, T-and Z-scores (mean ± s.d., respectively) were lower in inflammatory bowel disease patients than in irritable bowel syndrome controls (0.78 ± 0.12 vs. 0.90 ± 0.16, P ¼ 0.0046; ) 0.88 ± 0.92 vs. 0.12 ± 1.17, P ¼ 0.0018; ) 0.30 ± 0.89 vs. 0.61 ± 1.10, P ¼ 0.0030). Lumbar spine bone mineral density and T-scores were also significantly lower in patients than controls (0.98 ± 0.15 vs. 1.08 ± 0.13, P ¼ 0.0342; ) 1.05 ± 1.39 vs. ) 0.14 ± 1.19, P ¼ 0.0304). Compared with controls, the urinary deoxypyridinoline : creatinine ratio was increased (7.66 vs. 5.70 nmol ⁄ mmol, P ¼ 0.0163) and serum 25-hydroxy vitamin D was decreased (18.7 vs. 28.5 lg ⁄ L, P ¼ 0.0016); plasma osteocalcin and serum parathyroid hormone did not differ (P > 0.05). Conclusions: The bone mineral density is reduced at diagnosis, prior to corticosteroid treatment, in both Crohn's disease and ulcerative colitis. Our data suggest that this is attributable to increased resorption rather than decreased bone formation.

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The hormone erythropoietin (Epo) produced in the kidneys in response to hypoxia stimulates the production of red blood cells. We measured serum Epo levels in 26 healthy men over a 24-h period to determine whether Epo is secreted according to a circadian rhythm. Samples were collected every 2-4 h, and Epo was measured by using a radioimmunoassay (INCSTAR Epo-trac). To determine whether blood collection had any effect on Epo production, one-half of the subjects began the collection period in the morning and the other half in the evening. Exercise and the use of prostaglandin inhibitors were prohibited to eliminate fluctuations in Epo production in response to discrete stimuli. The daily Epo concentration for all subjects combined was 15.5 +/- 5.3 (SD) U/l. No significant circadian variation in serum Epo concentrations was observed in either group or when both groups were combined; however, a measure of individual variance was observed (mean deviation = 0.8 +/- 0.4 U/l).

IntroductionThe use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals.Materials and MethodsA set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed.ResultsNone of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR-145 correlated with nadir CD4+ T cell count.DiscussionNo associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection.

To characterize fluid and ion shifts during prolonged whole-body immersion, 16 divers wearing dry suits completed four whole-body immersions in 5 degrees C water during each of two 5-day air saturation dives at 6.1 msw. One immersion was conducted at 1000 (AM) and one at 2200 (PM) so that diurnal variations could be evaluated. Fifty-four hours separated the immersions, which lasted up to 6 h; 9 days separated each air saturation dive. Blood was collected before and after immersion; urine was collected for 12 h before, during, and after immersion for a total of 24 h. Plasma volume decreased significantly and to the same extent (approximately 17%) during both AM and PM immersions. Urine flow increased by 236.1 +/- 38.7 and 296.3 +/- 52.0%, urinary excretion of Na increased by 290.4 +/- 89.0 and 329.5 +/- 77.0%, K by 245.0 +/- 73.4 and 215.5 +/- 44.6%, Ca by 211.0 +/- 31.4 and 241.1 +/- 50.4%, Mg by 201.4 +/- 45.9 and 165.3 +/- 287%, and Zn by 427.8 +/- 93.7 and 301.9 +/- 75.4% during AM and PM immersions, respectively, compared with preimmersion. Urine flow and K excretion were significantly higher during the AM than PM. In summary, when subjects are immersed in cold water for prolonged periods, combined with a slow rate of body cooling afforded by thermal protection and enforced intermittent exercise, there is diuresis, decreased plasma volume, and increased excretions of Na, K, Ca, Mg, and Zn.

Experiments were conducted to determine the efficacy in stimulating and maintaining an immune response in the presence of maternal antibodies, compare the extent of the anamnestic responses to revaccination, and compare the maternal antibody response of 2- or 5-mL clostridial vaccination. In Exp. 1, 118 nursing calves were randomly assigned to receive a 2-mL (Alpha-7, A7) or a 5-mL clostridial vaccine (Ultrabac 7; UB7) at 50.4 +/- 15.30 (X +/- SD) d of age (d 0 = date of calving). Calves were revaccinated with the same treatment on d 170. Blood samples were collected from 10 calves of each treatment group on d 50, 170, and 191 to determine antitoxin units for Clostridium perfringens type C (PC) and D (PD) and agglutination titers for Cl. chauvoei (CC). The A7-treated calves tended (P< .10) to have higher PC units on d 170, an increased rate of change in PD units from d 170 to d 191 (P < .06), and a tendency (P < .10) for enhanced CC titers on d 191 compared with UB7-treated calves. In Exp. 2, 109 pregnant cows and 83 pregnant heifers were randomly assigned within a 2 x 2 x 2 factorial design. The main effects were dam age (cow or heifer), dam treatment (A7 or UB7), and calf treatment (A7 or UB7). Dams were vaccinated with A7 or UB7 d 124 prepartum (d -124) and d 53 after birth. At d 53.4 +/- 12.88, calves were vaccinated with A7 or UB7 (d 53). Calves were revaccinated with the same treatment on d 173. Blood samples were collected from 10 dams per treatment group on d -124, 53, and 173 and from their calves on d 53, 173, and 194. Cows had higher antitoxin levels for PC (P < .01) and PD (P < .05) than heifers. The A7-treated dams had higher (P < .01) PD units on d 53 and d 173 and CC on d 173 than did UB7-treated dams. Calves from A7-treated cows had higher (P < .03) PD units on d 53 than calves from UB7-treated cows. The A7-treated calves had higher titers for CC (P < .01) on d 173 than did UB7-treated calves, and this enhanced level seemed to continue to d 194 (P < .08). In conclusion, titers for clostridial diseases in 50- to 53-d-old calves can be enhanced if dams are vaccinated approximately 4 mo before calving, and 120 d between clostridial vaccinations seems to be too long for adequate protection.

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