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Thesis (MSc. (Companion Animal Clinical Studies))--University of Pretoria, 2000. / Also available in print format.

The work described in this thesis examines the renal excretion of nickel in humans and the Wistar Albino male rat. The renal clearance of nickel is characterized in two groups of electrolytic nickel-refinery workers. In the animal work, the mechanisms of nickel uptake in kidney tissue and its pathological consequences are investigated. Multi-void 24-h urine collections were obtained from 26 workers, as well as serum samples at the beginning and end of this sampling period. Nickel, ?[2]-microglobulin and creatinine concentrations were measured in both body fluids. In addition, specific gravity, protein and qualitative indices of kidney disfunction (by Dip Stick) were assessed in urine. Examination of the functional dependence in individuals of urinary nickel, creatinine and specific gravity on urine flow-rate indicates that specific gravity adjustment of spot-nickel voids is more appropriate than employing creatinine. The systematic strategy devised in this study to overcome concentration-dilution effects for nickel has wide application in biological monitoring. It is demonstrated that if the specific gravity values of spot urine voids in a group of 20 individuals are between 1.010 and 1.039, then the uncompensated uncertainty in specific-gravity adjusted urinary-nickel concentrations does not exceed +/- 10% (95% Confidence Level). Nickel clearance studies and the determination of nickel in serum ultrafiltrates indicated that 24 +/- 6% of serum nickel is available for renal filtration, of which 65% on average is reabsorbed in the human kidney. It is concluded for the nickel-refinery workers studied, that there was little evidence of kidney dysfunction. Studies with rat renal slices and isolated proximal tubules showed that the uptake of Ni[2+] and its histidine complexes is probably passive. Ni(His)[2] reduced the uptake of L-histidine and proline, but not of thymidine. The renal accumulation of nickel from nontoxic i.v. doses of [63]Ni(His)[2] (6 mug Ni kg[-1]) was followed by rapid subcellular clearance during the 24-h period after injection. Autoradiography of the nephron illustrated that only the S3 segment of the proximal tubule accumulated and retained nickel. There was no evidence of nephrotoxicity in the histopathological examination of these tissues. By contrast, high i.p. doses (3 and 6 mg Ni kg[-1] induced a decrease in Bowman's space and minor changes along the entire length of affected nephrons. Compartmentalization of nickel within subcellular fractions of the rat kidney is interpreted in terms of an "Equilibrium" model for metal- ion uptake under steady state conditions (i.e., at fixed pH, redox potential, intracellular and extracellular ligand concentrations). Effectively, nickel distribution is determined by thermodynamic parameters such as complex stability. The human and animal evidence support a passive mechanism of nickel reabsorption in the kidney. Simple pulmonary deposition and absorption considerations in man suggest that the dose of nickel acquired during an 8- h shift of work at a Threshold Limit Value (TLV) of 0.1 mg Ni m[-3] is roughly equivalent to the 6 mug Ni kg[-1] dose used in the rat study. Therefore, the absence of signs of significant nephrotoxicity in both the human and animal models appears to be consistent.

Considerable changes have occurred in environmental regulations in recent years, only one of which is the requirement of stand alone heifer operations and feedlots to carry environmental permits. While growth of heifers is a widely researched topic, publications concerning nutrient utilization, partitioning, and excretion are scarce and are becoming necessary. That combined with the fact that feeding programs for heifers are highly variable from region to region and even from farm to farm indicated the need to examine the effects of diet on nutrient utilization. Therefore, the objective of this work was to evaluate how differences in levels of dietary protein and energy will affect growth and nutrient utilization in heifers from birth to calving. Two projects were conducted, one in 20 month old bred heifers where forage level in the diet was altered to provide the required nutrients in less feed and one in young calves where energy and protein content of the milk replacer was altered. Three diets were fed to 18 (n=6), 20 month old heifers who were in late gestation; the first was the high forage (HF) ration which was 90.7% forage and 9.3% concentrate, the second was a by-product (BP) ration which was designed to have the same level of fiber as the HF ration, however soybean hulls and cottonseed hulls were added at the sacrifice of the grain mix which increased the fiber content; the last ration was the low forage (LF) which was 54.7% concentrate and 45.3% forage and was fed at ~89% of the ad libitum intake of heifers fed the HF ration. Heifers fed the HF ration had greater fecal excretion compared to those fed LF, however heifers fed the LF ration exceeded the heifers fed HF and BP by 4.5 and 2.5 times, respectively, in urine volume excretion (40.2 vs. 8.9 and 16.9 kg/d, respectively). Although total N excretion (kg/d) was not different, heifers fed the LF ration tended to partition more N to urine than to feces. Phosphorus excretion in the feces was not different, however heifers fed HF and BP tended to have greater fecal P (P < 0.06). Urinary P excretion was less in heifers fed HF and BP compared to LF, however these heifers were excreting as much urinary P as a lactating cow. Calves were purchased from a commercial dairy at 3 d old (&#177; 1d) and transported to the VT Dairy Center. They remained on study until 63 d when they were harvested for body composition. Four treatment diets were fed; a control milk replacer (24/17; 24% CP, 17% Fat), a high protein, low fat (32/17; 32% CP, 17% Fat), a high protein, high fat (31/24, 31% CP, 24% fat), and that same 31/24 milk replacer fed at 1460 g/d powder (31/24+). Calves were offered a 20% cottonseed hull starter at 1 d after arrival to the VT Dairy Center. Calves fed 24/17 consumed more starter than those fed the other milk replacers and therefore had a lower apparent digestibility and greater fecal excretion. Fecal N excretion was not different, although calves fed 24/17 tended to have greater fecal N excretion. Urinary N excretion was higher in calves fed 31/24+ compared to those fed 31/24. Total N excretion and N retention were not different. Empty body weight (EBW) gain was greater in calves fed 31/24+ compared to 31/24, however those same calves also had a higher percent of EBW as fat. Calves fed 32/17 had the most lean gain (in the form of N gain) compared to those fed extra energy (31/24) and also had a higher N as a percent of EBW. Limit feeding Holstein heifers late in gestation did not reduce nutrient excretion, however, more digestible nutrients were available to the heifer and fetus. Heifers in late gestation are likely over fed P and therefore excrete nearly everything they consume which has negative implications for nutrient management planning. Calves fed a low protein, low fat milk replacer did not grow as well as calves fed higher protein. Nitrogen retention and CP gain were higher when protein was at least 31% and fat was at least 17%. Feeding fat over 17% only increased fat gain and not CP gain. Overall, paying for extra nutrients in bred heifer diets seemed to be beneficial, however, feeding above 31% CP and 17% fat increased nutrient loss to the environment. / Ph. D.

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Bibliography: leaves 183-202