PSI-11 Effects of a supplemental water source and trace-mineral based electrolyte drinking solution on intake and blood cell count of newly received feedlot calves

Oral hydration therapy has been used to improve performance and health of newly received feedlot calves; however, little is known regarding water intake (WI) following arrival at the feedlot. Our objective was to evaluate WI of newly received feedlot calves provided a supplemental water source or a novel nutritional rehydration solution during initial 3 days following arrival. Crossbred heifers (n=180; initial BW = 237 ± 23 kg) were individually weighed after 16 h fasting and sorted into 12 pens (4 pens/treatment). Treatments were: 1) Control (CON): water provided through standard in-pen automatic waterer only (Richie CM480; one waterer/pen); 2) Supplemental water (SUPW): CON + water provided with one additional stock tank/pen; 3) Novel nutritional rehydration solution (NRS): trace-mineral based drinking solution provided with one stock tank/pen as the only water source. Treatments were provided from days 0 to 3 after which supplemental tanks were removed. From days 4 to 14 all heifers had access to the standard in-pen automatic waterer only. The WI was measured daily throughout the trial and BW was recorded at days 0 and 14. Whole blood was collected (5 heifers/pen) on days 0, 3, and 14. Treatments had no effect on DMI or ADG (P ≥ 0.15). SUPW and NRS had greater WI than CON from days 0 to d 3 (P ≤ 0.001), but not from days 4 to 14 nor from days 0 to 14 (P = 0.69). No treatment effect or treatment × day interactions were observed for total red (RBC) or white blood cell counts (WBC; P ≥ 0.19); however, a day effect was present (P < 0.001) and RBC and WBC linearly decreased from day 0 to 14 (P < 0.05). Our preliminary results indicate that providing a supplemental source of water during the initial 3 d after arrival increased total WI and may facilitate rehydration in stressed calves following transit.

Vitamin D oral intermittent treatment (DO IT) study, a randomized clinical trial with individual loading regimen

Comparison of several regimens of oral vitamin D including an individually calculated loading regimen with the aim of achieving serum values > 75 nmol/l. Interventional, randomized, 3-arm study in vitamin D-deficient outpatients. Participants were allocated to supplementation of 24,000 IU vitamin D monthly over three months, using either a monthly drinking solution (Vi-De 3) or capsule (D3 VitaCaps), or an individualized loading regimen with the capsules taken weekly. For the loading regimen, the cumulative dose was calculated according to baseline 25-hydroxy-vitamin D (25(OH)D) serum value and body weight. Main inclusion criteria were age ≥ 18 years and 25(OH)D serum concentration < 50 nmol/l. The primary outcome was 25(OH)D serum concentration one week after treatment termination. Secondary endpoints were patient’s preferences and adverse events. Full datasets were obtained from 52 patients. Mean 25(OH)D values were statistically significant higher after a loading regimen compared to a monthly administration of 24,000 IU vitamin D (76.4 ± 15.8 vs 61.4 ± 10.8 nmol/l; p < 0.01). All patients treated with the loading regimen reached sufficient 25(OH)D values > 50 nmol/l. Serum 25(OH)D values > 75 nmol/l were observed more frequently in patients taking the loading regimen (47% vs 11% drinking solution vs 12% capsules). Vitamin D-related adverse effects did not occur in any treatment groups. Capsules were preferred by 88.5% of the patients. Compared to treatments with monthly intake of 24,000 IU vitamin D, the intake of an individually calculated weekly loading regimen was able to raise serum concentrations > 50 nmol/l in all cases within a safe range.

Early Inflammatory Responses in Experimental Cardiac Hypertrophy and Fibrosis: Effects of 11β-Hydroxysteroid Dehydrogenase Inactivation

In epithelial tissues such as kidney, mineralocorticoid receptors (MR) are protected against glucocorticoid occupancy by the enzyme 11β-hydroxysteroid dehydrogenase (11βHSD) type 2. If the enzyme is congenitally inactive, or blocked by carbenoxolone, physiologic glucocorticoids act as MR agonists in such tissues. In most nonepithelial tissues, including cardiomyocytes, 11βHSD2 is expressed at minimal levels; in these tissues physiologic glucocorticoids act as MR antagonists, with the basis for this tissue selectivity currently unknown. Vascular smooth muscle cells (VSMC) express MR and 11βHSD1/2, with 11βHSD1 reported to show uncharacteristic oxidase activity, so that VSMC thus constitute a potential physiologic aldosterone target tissue. Because mineralocorticoid/salt administration triggers marked inflammatory responses in coronary vasculature, we reasoned that VSMC (like epithelial) MR may be activated by glucocorticoids if the protective enzyme is blocked. We thus gave uninephrectomized rats 0.9% NaCl solution to drink, and deoxycorticosterone (DOC, as a single 20 mg sc dose) or carbenoxolone (CBX, 2.5 mg/d in the drinking solution). Both DOC and CBX increased systolic blood pressure, heart, and kidney weight, and expression of cyclooxygenase 2, ED-1-positive macrophages, and osteopontin, with effects of both DOC and CBX blocked by the selective MR antagonist eplerenone. These findings suggest that local glucocorticoid excess, reflecting lower VSMC 11βHSD1/2 activity may mimic systemic mineralocorticoid excess, and play a direct etiologic role in coronary vascular inflammatory responses under circumstances of a high salt intake.

Conditioned suppression of contact sensitivity is independent of sympathetic splenic innervation

The present study investigated the role of sympathetic innervation of the spleen in conditioned suppression of a contact hypersensitivity (CHS) reaction. Behavioral conditioning was achieved by pairing saccharin drinking solution (conditioned stimulus, CS) with injection of cyclosporin A (CsA, 20 mg/kg; unconditioned stimulus, UCS). Four days after sensitization of the animals by application of a 5% 2,4-dinitrochlorobenzene (DNCB) to abdominal skin, the animals were challenged by applying a 1% DNCB solution to the ear. The CHS response was monitored by measuring the degree of ear swelling. Saccharin re-presentation reduced ear swelling to a magnitude that approached that achieved by CsA treatment. Histological examination demonstrated that the conditioned reduction of ear swelling was produced by a reduced leukocyte infiltration of the ear. Prior sympathetic denervation of the spleen did not alter the conditioned suppression of the CHS response. These data indicate that behavioral conditioning using CsA produces alterations of CHS that, unlike conditioned prolongation of heart allograft survival, are independent of sympathetically regulated conditioned alterations in the spleen.

Prostacyclin increases distal tubule HCO3 secretion in the rat

We examined whether prostacyclin (PGI2), a prostaglandin synthesized in the renal cortex that increases adenosine 3',5'-cyclic monophosphate levels in distal nephron epithelia, mediates increased HCO3 secretion in in vivo perfused distal tubules of anesthetized rats given dietary HCO3. Animals eating a minimum electrolyte diet given 80 mM NaHCO3 drinking solution increased urine excretion of 6-keto-PGF1 alpha, a PGI2 metabolite, by 2.6 +/- 0.3-fold compared with those drinking distilled H2O. NaHCO3 animals infused with indomethacin to inhibit PGI2 synthesis had lower HCO3 secretion than those without indomethacin (-8.9 +/- 0.9 vs. -18.7 +/- 1.8 pmol.mm-1.min-1, P < 0.01). By contrast, NaHCO3 animals infused with both PGI2 and indomethacin had higher HCO3 secretion than those given indomethacin alone (-16.0 +/- 1.5, P < 0.02 vs. indomethacin group). HCO3 secretion was not different between controls with and without indomethacin but was higher in the PGI2 + indomethacin compared with the indomethacin alone controls (-11.2 +/- 1.2 vs. -4.5 +/- 0.5, P < 0.01). The data show that PGI2 increases distal tubule HCO3 secretion in rats and suggest that this agent contributes to the increased distal tubule HCO3 secretion induced by dietary HCO3.

Determinants of cardiac fibrosis in experimental hypermineralocorticoid states

Uninephrectomized rats maintained on 1.0% NaCl to drink and infused with aldosterone (0.75 microgram/h) for 8 wk have previously been shown to develop hypertension, cardiac hypertrophy, and cardiac fibrosis. In the present study we have shown that K+ supplementation (1.0% NaCl plus 0.4% KCl drinking solution) alters neither the interstitial nor the perivascular fibrotic response to mineralocorticoid treatment. Second, rats receiving 0.75 microgram/h 9 alpha-fluorocortisol, a mineralocorticoid and glucocorticoid agonist, respond with hypertension and cardiac fibrosis without cardiac hypertrophy. Finally, intracerebroventricular infusion of the mineralocorticoid receptor antagonist RU-28318 blocks blood pressure elevation, but not cardiac hypertrophy or fibrosis, when aldosterone is coinfused peripherally. We conclude that the myocardial fibrosis observed in response to chronic mineralocorticoid elevation and salt loading is a humorally mediated event independent of hypokalemia, hypertension, and cardiac hypertrophy. It remains to be determined whether the fibrosis observed in the presence of excess salt represents a direct (e.g., cardiac) effect of mineralocorticoid hormones or one mediated via a primary action on classical epithelial aldosterone target tissues (e.g., kidney).

Impaired very low-density lipoprotein-triglyceride catabolism in acute and chronic fructose-fed rats

Very low-density lipoprotein (VLDL)-triglyceride (TG) catabolism was compared in rats given chow and either a 10% fructose (F) or 10% glucose (G) drinking solution for both acute (A) (16 h) and chronic (C) (14 days) periods. VLDL-TG were labeled in F and G donor rats using different isotopic forms of glycerol. A mixture of the VLDLs was injected into F and G recipients and the decline in plasma TG radioactivities used as a measure of clearance. VLDL-TG from F donors was cleared more slowly than VLDL-TG from G donors. In F recipients, the half-life of VLDL-TG from either F or G donors was longer than that in G fed recipients. VLDL from the AF group, had a lower apoprotein E-to-C apoprotein ratio (E/C) than VLDL from the AG group. VLDL from both F groups had a lower E/C than did that from control rats. The E/C negatively correlated with plasma VLDL-TG. CF and CG VLDL had elevated CIII0 and lower CIII3 levels compared with their respective A groups and controls. The ratio of VLDL apoprotein B100, B95, and B48 did not differ between treatments. AF and AG VLDL were larger and enriched in TG compared with control or the CF and CG groups. The saturated fatty acid-to-unsaturated fatty acid ratio in VLDL-TG was higher in the G groups and AF group compared with controls. The present study suggests that the E/C may be lowered as a result of F consumption, thereby contributing to the impairment in VLDL-TG removal.