Serum Urea Nitrogen Concentrations Research Articles

Effect of the amount of body condition loss from the dry to near calving periods on the subsequent body condition change, occurrence of postpartum diseases, metabolic parameters and reproductive performance in Holstein dairy cows

We investigated the effect of body condition loss from the dry to near calving periods on the subsequent body condition change, the occurrence of postpartum diseases, the serum metabolic parameters total cholesterol, triglyceride, glucose, and urea nitrogen and the number of days to first breeding after calving in Holstein dairy cows. Body condition scoring (using a 5-point scale with quarter-point divisions) was performed on 67 pregnant Holstein dairy cows. Cows were scored once for body condition during the dry period (prepartum day 35±16), near calving (postpartum day 5±4), and subsequently at months 1 (±day 4), 2 (±day 5), 3 (±day 5), and 4 (±day 4) of lactation. At the same time, blood samples were collected to evaluate serum total cholesterol, triglyceride, glucose and urea nitrogen concentrations. Cows were categorized based on body condition loss from the dry to near calving periods into two groups: the moderate condition loss group (0–0.75 points, n=41), or the marked condition loss group (1.0–1.5 points, n=26). Regular reproductive health examination was conducted by the same investigator once a week. The marked condition loss group lost more body condition ( P<0.01) than the moderate condition loss group consistently until month 1 of lactation. The recovery of body condition in the marked condition loss group was more delayed ( P<0.01) than in the moderate condition loss group from months 1 to 4 of lactation. The occurrence of metritis and metabolic diseases (including abomasal displacement, milk fever, ketosis) was greater ( P<0.01) in the marked condition loss group (62 and 23%) than in the moderate condition loss group (27 and 2%), respectively. The total cholesterol concentration was lower ( P<0.05) in the marked condition loss group (167±5.3 mg/dl) than in the moderate condition loss group (183±5.8 mg/dl) at month 1 of lactation, however, the cholesterol levels at the other periods were not different ( P>0.05) between the two groups. The triglyceride, glucose, and urea nitrogen concentrations were not different ( P>0.05) from the dry period to month 4 of lactation between the two groups. The number of days to first breeding after calving was longer ( P<0.05) in the marked condition loss group (103±7.8 day) than in the moderate condition loss group (87±5.3 day). We conclude that marked body condition loss from the dry to near calving periods results in the increased occurrence of postpartum metabolic and reproductive diseases, decreased serum total cholesterol concentrations at month 1 of lactation and a longer interval to first breeding after calving in Holstein dairy cows, probably due to the more severe energy deficit reflected by unfavorable body condition score change during early lactation.

Stocking Rate Effects on Goats: A Research Observation

Knowledge on the ecological effects of goat grazing on arid rangeland is far from complete, and specifically there is little scientific information on effects of heavy goat grazing on arid ecosystems. One objective of this study was to determine botanical composition of dairy-type goat diets on heavily (1.5 ha per goat) and lightly (15 ha per goat) grazed Chihuahuan desert range by fecal microhistological analysis. A second objective was to determine whether vegetation cover, some blood metabolites and mineral levels, as well as fertility of goats were sensitive to high grazing pressure. The lightly grazed site had more (P < 0.05) total foliage cover (38.6 vs 30.4%) than the overstocked pasture. Total shrubs in diets of goats was greater (86.4 vs 72.4 in the late-dry period, 78.6 vs 42.1 in late-wet period; P < 0.05) on the heavily stocked pasture than the lightly stocked pasture. Forbs in the diets were lower (P < 0.10) in the late-dry (11.4 vs 21.5%), early-wet (55.4 vs 64.0%) and late-wet period (15.0 vs 45.8%) on the heavily stocked pasture than the lightly stocked pasture. Substantially lower (P < 0.01) serum glucose, urea nitrogen, Zn and Mg concentration at the onset of the breeding period in goats on the heavily stocked pasture, compared to goats on the lightly grazed pasture resulted in a higher (P < 0.01) abortion rate (22 vs 12%) and consequently a lower (P < 0.05) kidding rate (42 vs 55%). We concluded that overstocking with goats greatly reduced shrub and grass cover. Also, decades of continuously high grazing pressure has forced goats to alter diet selection pattern by consuming more resinous, toxic, and coarse species. This switch was associated with a lower nutritional status, a negative daily weight gain, lower body condition score in the late-wet period, and lower fertility on heavily grazed range.

Stocking rate effects on goats: A research observation

Knowledge on the ecological effects of goat grazing on arid rangeland is far from complete, and specifically there is little scientific information on effects of heavy goat grazing on arid ecosystems. One objective of this study was to determine botanical composition of dairy-type goat diets on heavily (1.5 ha per goat) and lightly (15 ha per goat) grazed Chihuahuan desert range by fecal microhistological analysis. A second objective was to determine whether vegetation cover, some blood metabolites and mineral levels, as well as fertility of goats were sensitive to high grazing pressure. The lightly grazed site had more (P &lt; 0.05) total foliage cover (38.6 vs 30.4%) than the overstocked pasture. Total shrubs in diets of goats was greater (86.4 vs 72.4 in the late-dry period, 78.6 vs 42.1 in late-wet period; P &lt; 0.05) on the heavily stocked pasture than the lightly stocked pasture. Forbs in the diets were lower (P &lt; 0.10) in the late-dry (11.4 vs 21.5%), early-wet (55.4 vs 64.0%) and late-wet period (15.0 vs 45.8%) on the heavily stocked pasture than the lightly stocked pasture. Substantially lower (P &lt; 0.01) serum glucose, urea nitrogen, Zn and Mg concentration at the onset of the breeding period in goats on the heavily stocked pasture, compared to goats on the lightly grazed pasture resulted in a higher (P &lt; 0.01) abortion rate (22 vs 12%) and consequently a lower (P &lt; 0.05) kidding rate (42 vs 55%). We concluded that overstocking with goats greatly reduced shrub and grass cover. Also, decades of continuously high grazing pressure has forced goats to alter diet selection pattern by consuming more resinous, toxic, and coarse species. This switch was associated with a lower nutritional status, a negative daily weight gain, lower body condition score in the late-wet period, and lower fertility on heavily grazed range.

Detrimental Effects of a High Fat Diet in Early Renal Injury Are Ameliorated by Fish Oil in Han:SPRD-cy Rats

Dietary fish oils containing (n-3) fatty acids can modulate renal inflammatory injury. We previously demonstrated that a high fat (HF) diet worsens early renal disease progression in the Han:SPRD-cy rat model of polycystic kidney disease (PKD). Therefore, using HF (20 g/100 g diet) and low fat (LF; 5 g/100 g diet) diets, we compared the effects of menhaden oil (MO), soybean oil (SO) and cottonseed oil (CO) on renal function and histology in male Han:SPRD-cy rats fed the diets for 6 wk in the early stages of renal disease. Overall, rats fed HF compared with those fed LF diets had larger kidneys, more renal fibrosis and lower creatinine clearance (main effects of fat level). Rats fed MO rather than CO and SO diets had significantly lower kidney weights, kidney water content, cyst volumes and serum cholesterol and triglyceride concentrations (main effects of fat type). Rats fed MO diets also had less renal fibrosis than those fed CO diets, but the least fibrosis was in rats fed SO diets. Analysis of simple effects (due to interactions between fat level and type) revealed that HF diets increased renal inflammation in rats fed CO diets, but reduced inflammation was present in those fed SO and MO diets; HF diets also increased compared with LF diets serum urea nitrogen concentrations in rats fed the MO and CO diets, but not the SO diet. These results confirm that high dietary fat worsens early disease progression in this model of renal disease, and further demonstrate that diets with oils containing (n-3) fatty acids ameliorate some of the detrimental effects of a high fat diet.

Factors associated with adverse outcomes in children with diabetic ketoacidosis-related cerebral edema

Objective: To investigate the relation between outcomes of children with diabetic ketoacidosis (DKA)-related cerebral edema and baseline clinical features and therapeutic interventions for treatment of cerebral edema. Study design: All children ≤18 years old with DKA and cerebral edema (n = 61) were retrospectively identified from 10 pediatric centers between 1982 and 1997. Demographic, biochemical, and therapeutic data were collected. Ordinal logistic regression analysis was used to identify factors associated with the clinical outcome (death or persistent vegetative state; mild to moderate neurological disability; or normal) after adjusting for known risk factors for the development of cerebral edema as well as the degree of neurologic depression at the time of diagnosis of cerebral edema. Results: Seventeen (28%) children died or survived in a vegetative state; 8 (13%) survived with mild to moderate neurologic disabilities; and 36 (59%) survived without sequelae. Factors associated with poor outcomes included greater neurologic depression at the time of diagnosis of cerebral edema, a high initial serum urea nitrogen concentration, and intubation with hyperventilation to a PCO2 <22 mm Hg. Conclusions: After adjusting for potential confounding variables and the degree of neurologic compromise at the initiation of therapy, intubation with hyperventilation is associated with adverse outcomes of DKA-related cerebral edema. Greater neurologic depression at the time of diagnosis of cerebral edema and a higher initial serum urea nitrogen concentration are also associated with poor outcome. (J Pediatr 2002;141:793-97)

Diuretics, mortality, and nonrecovery of renal function in acute renal failure.

Acute renal failure is associated with high mortality and morbidity. Diuretic agents continue to be used in this setting despite a lack of evidence supporting their benefit. To determine whether the use of diuretics is associated with adverse or favorable outcomes in critically ill patients with acute renal failure. Cohort study conducted from October 1989 to September 1995. A total of 552 patients with acute renal failure in intensive care units at 4 academic medical centers affiliated with the University of California. Patients were categorized by the use of diuretics on the day of nephrology consultation and, in companion analyses, by diuretic use at any time during the first week following consultation. All-cause hospital mortality, nonrecovery of renal function, and the combined outcome of death or nonrecovery. Diuretics were used in 326 patients (59%) at the time of nephrology consultation. Patients treated with diuretics on or before the day of consultation were older and more likely to have a history of congestive heart failure, nephrotoxic (rather than ischemic or multifactorial) origin of acute renal failure, acute respiratory failure, and lower serum urea nitrogen concentrations. With adjustment for relevant covariates and propensity scores, diuretic use was associated with a significant increase in the risk of death or nonrecovery of renal function (odds ratio, 1.77; 95% confidence interval, 1.14-2.76). The risk was magnified (odds ratio, 3.12; 95% confidence interval, 1.73-5.62) when patients who died within the first week following consultation were excluded. The increased risk was borne largely by patients who were relatively unresponsive to diuretics. The use of diuretics in critically ill patients with acute renal failure was associated with an increased risk of death and nonrecovery of renal function. Although observational data prohibit causal inference, it is unlikely that diuretics afford any material benefit in this clinical setting. In the absence of compelling contradictory data from a randomized, blinded clinical trial, the widespread use of diuretics in critically ill patients with acute renal failure should be discouraged.

Renal reabsorption of magnesium and calcium by cattle with renal tubular dysplasia

The concentrations of magnesium and calcium in the serum and urine and their rates of clearance were determined in cattle with renal tubular dysplasia, an autosomal recessive hereditary disease associated...

Effect of Replacing Corn Silage with Annual Ryegrass Silage on Nutrient Digestibility, Intake, and Milk Yield for Lactating Dairy Cows

Twenty Holstein cows were used in an 8-wk randomized block design study to determine the effects of replacing corn silage with ryegrass silage on nutrient intake, apparent digestion, milk yield, and milk composition. The 8-wk trial consisted of a 2-wk preliminary period followed by a 6-wk collection period. Experimental diets were formulated to provide 55.5% of the total dry matter (DM) as forage. Ryegrass silage was substituted for 0, 35, 65, and 100% of DM provided by corn silage. Dietary concentrations of neutral detergent fiber (NDF) and acid detergent fiber (ADF) increased as ryegrass silage replaced corn silage. Intake of DM and crude protein (CP) was similar for all treatments, but intake of NDF and ADF increased linearly as ryegrass silage replaced corn silage. Apparent digestibility of DM declined linearly, whereas digestibility of CP increased linearly as ryegrass silage replaced corn silage. Apparent digestibility of NDF and ADF was highest for the diets in which ryegrass or corn silages provided all of the forage, resulting in a quadratic response. Dry matter intake was not different among treatments. Yield of milk, fat, and protein increased as ryegrass silage replaced corn silage. No differences were observed for body weight change, body condition score, and serum urea nitrogen concentration, but serum glucose concentration increased with increasing dietary proportion of ryegrass silage. These results indicate that substituting ryegrass silage for a portion or all of the corn silage in diets fed to lactating dairy cows can improve yield of milk and components.

Effects of growth hormone treatment on the pituitary expression of GHRH receptor mRNA in uremic rats

A decreased ability of pituitary cells to secrete growth hormone (GH) in response to growth hormone releasing hormone (GHRH) stimulation has been shown in young uremic rats. The aim of the current study was to examine the effect of uremia and GH treatment on pituitary GHRH receptor expression. Pituitary GHRH receptor mRNA levels were analyzed by RNase protection assay in young female rats made uremic by subtotal nephrectomy, either untreated (UREM) or treated with 10 IU/kg/day of GH (UREM-GH), and normal renal function animals fed ad libitum (SAL) or pair-fed with the UREM group (SPF). Rats were sacrificed 14 days after the second stage nephrectomy. Renal failure was confirmed by concentrations (X +/- SEM) of serum urea nitrogen (mmol/L) and creatinine (micromol/L) in UREM (20 +/- 1 and 89.4 +/- 4.5) and UREM-GH (16 +/- 1 and 91.4 +/- 6.9) that were much higher (P < 0.001) than those of sham animals (SAL, 3 +/- 0 and 26.5 +/- 2.2; SPF, 4 +/- 0 and 26.5 +/- 2.1). UREM rats became growth retarded as shown by a daily longitudinal tibia growth rate below (P < 0.05) that observed in SAL animals (156 +/- 3 vs. 220 +/- 5 microm/day). GH treatment resulted in significant growth rate acceleration (213 +/- 6 microm/day). GHRH receptor mRNA levels were no different among the SAL (0.43 +/- 0.03), SPF (0.43 +/- 0.08) and UREM (0.44 +/- 0.04) groups, whereas UREM-GH rats had significantly higher values (0.72 +/- 0.07). The status of pituitary GHRH receptor is not modified by nutritional deficit or by severe uremia causing growth retardation. By contrast, the growth promoting effect of GH administration is associated with stimulated GHRH receptor gene expression.

Accuracy of Serum β‐Hydroxybutyrate Measurements for the Diagnosis of Diabetic Ketoacidosis in 116 Dogs

The aim of this study was to evaluate the accuracy of serum β‐hydroxybutyrate (β‐OHB) measurements for the diagnosis of diabetic ketoacidosis (DKA) in dogs. One hundred sixteen diabetic dogs were prospectively enrolled in the study: 18 insulin‐treated (IT) diabetic dogs that had a positive urine ketone test and 88 untreated, newly diagnosed diabetic dogs. Venous blood gas tensions and pH, serum glucose and urea nitrogen (SUN), and electrolyte (Na+, Cl‐, and K+) and urine acetoacetate (AA) concentrations were measured concurrently with serum β‐OHB concentrations. On the basis of laboratory findings, the patients were assigned to 1 of 3 groups: diabetic ketoacidosis (n = 43); diabetic ketosis (DK, n = 41); and nonketotic diabetes (NDK, n = 31). Serum β‐OHB concentrations differed significantly (P &lt; .001) among the study groups. Although marked differences in β‐OHB concentrations were found, a considerable overlap exists between the distributions of dogs with DK and those with DKA. The overall accuracy of β‐OHB determination as a diagnostic test for DKA, determined by the area under the receiver operating characteristic (ROC) curve, was 0.92. In the 1.9‐ to 4.8‐mmol/L range, serum β‐OHB determination sensitivity varied from 100 to 35.7%, whereas specificity varied from 39 to 100%. The cutoff value of 3.8 mmol/L showed the best equilibrium between specificity (95%), sensitivity (72%), and likelihood ratio (14.8). We concluded that the quantitative measurement of serum β‐OHB may be a potential tool for diagnosing and monitoring ketosis and ketoacidosis in diabetic dogs.

Effect of dietary methionine to lysine ratio on lactation performance of first and second parity Yorkshire and Hampshire lean genotype sows

A total of 196 Yorkshire (Y) sows, 137 of first and 59 of second parity, and 97 Hampshire (H) sows, 55 of first and 42 of second parity, were used to determine the effect of increased dietary amino acids and two methionine-to-lysine ratios on sow lactation performance. The three treatment diets were: (1) a barley-wheat-soybean meal diet containing lysine at 0.43 g MJ-1 DE with no supplemental amino acids, 2) the same as diet 1, except the lysine content was increased to 0.68 g MJ-1 DE with supplemental threonine and methionine providing threonine and methionine to lysine ratios of 0.60 and 0.26, respectively, and 3) the same as diet 2, except with an increased methionine-to-lysine ratio of 0.30. All diets were fed as pellets, ad libitum in self-feeders, with free access to drinking water during a 28-d lactation period. Nursing piglets were given creep feed after 14 d of age. The average daily feed intake increased during lactation, and it was higher (P &lt; 0.05) in the second than the first parity sows. Feeding diets 2 and 3 increased (P &lt; 0.05) sow lactation weight and backfat gains, compared to diet 1 for both breeds. Feeding diet 3 increased (P &lt; 0.05) the sow lactation weight and backfat gains and piglet weight gains in the second parity Y sows, but not H sows. Post-weaning sow weight loss and weaning to estrus interval were not different (P &gt; 0.10) among the diets in both breeds. Feeding diets 2 and 3 decreased (P &lt; 0.05) the serum urea nitrogen concentration in Y sows indicating less amino acid catabolism. The results indicated that a dietary methionine-to-lysine ratio higher than 0.27 was not beneficial in maximizing lactation performance of modern lean genotype sows. Key words: Sows, lactation, ideal amino acid, Yorkshire, Hampshire, piglet

Contrast Induced Nephropathy after Angiography

Contrast-induced nephropathy (CIN), an acute decline in renal function after the administration of intravenous contrast in the absence of other causes,1 is the third leading cause of acute renal failure in hospitalized patients.2 The onset of CIN is usually within 24 hours of contrast exposure, asymptomatic, nonoliguric, and recognized only by rising serum urea nitrogen and creatinine concentrations. In most patients, the decline in renal function is transient; in rare patients, however, irreversible renal dysfunction occurs.

Increased parenteral amino acid administration to extremely low-birth-weight infants during early postnatal life.

Early administration of parenteral amino acids to infants with extremely low birth weight (birth weight < or = 1,000 g) has been encouraged to foster growth. However, excessive intravenous intake of amino acids may cause metabolic acidosis and uremia in extremely low birth weight infants. The hypothesis for this study was that extremely low birth weight infants would tolerate slightly increased early postnatal parenteral amino acid administration and benefit. The peak daily parenteral amino acid dosage was increased from 3 g/kg (standard group) to 4 g/kg (modified group). The corrected parenteral amino acid dosage was computed to account for enteral protein intake and keep the combined daily intravenous amino acid and enteral protein intake at or below 3 g . kg -1 . d -1 in the standard group and 4 g . kg -1 . d -1 in the modified group. The primary outcome measure was plasma bicarbonate concentration as an indicator of acid-base status. Data were collected for patient demographics, nutritional intake, serum bicarbonate and serum urea nitrogen concentrations, and outcome. The corrected parenteral amino acid intake of the modified group was 16% greater at postnatal week 1 (3.30 +/- 0.83 g . kg -1 . d -1; mean, +/-1 SD) and 18% greater (3.86 +/- 0.94 g . kg -1 . d -1 ) at postnatal week 2 than the parenteral amino acid intake of the standard group. In the modified group, the mean serum bicarbonate concentration was 19.1 +/- 1.8 mEq/dL at week 1 and 23.9 +/- 2.9 mEq/dL at week 2, with no difference between the groups. At week 1, serum urea nitrogen concentrations were the same in both groups. The mean serum urea nitrogen concentration of the modified group at postnatal week 2 (18.2 +/- 8.8 mg/dL) was unchanged from postnatal week 1, but was greater than that of the standard group at postnatal week 2. Weight gain was the same in both groups. Corrected parenteral amino acid intake at postnatal week 1 correlated directly with weight gain from birth to postnatal week 2 ( P < 0.03) in both groups. Infants with extremely low birth weight tolerated parenteral amino acid intake of approximately 4 g . kg -1 . d -1. Mild increases of mean serum urea nitrogen concentration and mean weight gain were associated with increased parenteral amino acid administration without significant acidosis.

Increased Parenteral Amino Acid Administration to Extremely Low‐Birth‐Weight Infants During Early Postnatal Life

ABSTRACTBackgroundEarly administration of parenteral amino acids to infants with extremely low birth weight (birth weight ≤1,000 g) has been encouraged to foster growth. However, excessive intravenous intake of amino acids may cause metabolic acidosis and uremia in extremely low birth weight infants. The hypothesis for this study was that extremely low birth weight infants would tolerate slightly increased early postnatal parenteral amino acid administration and benefit.MethodsThe peak daily parenteral amino acid dosage was increased from 3 g/kg (standard group) to 4 g/kg (modified group). The corrected parenteral amino acid dosage was computed to account for enteral protein intake and keep the combined daily intravenous amino acid and enteral protein intake at or below 3 g · kg−1 · d−1 in the standard group and 4 g · kg−1 · d−1 in the modified group. The primary outcome measure was plasma bicarbonate concentration as an indicator of acid–base status. Data were collected for patient demographics, nutritional intake, serum bicarbonate and serum urea nitrogen concentrations, and outcome.ResultsThe corrected parenteral amino acid intake of the modified group was 16% greater at postnatal week 1 (3.30 ± 0.83 g · kg−1 · d−1; mean, ±1 SD) and 18% greater (3.86 ± 0.94 g · kg−1 · d−1) at postnatal week 2 than the parenteral amino acid intake of the standard group. In the modified group, the mean serum bicarbonate concentration was 19.1 ± 1.8 mEq/dL at week 1 and 23.9 ± 2.9 mEq/dL at week 2, with no difference between the groups. At week 1, serum urea nitrogen concentrations were the same in both groups. The mean serum urea nitrogen concentration of the modified group at postnatal week 2 (18.2 ± 8.8 mg/dL) was unchanged from postnatal week 1, but was greater than that of the standard group at postnatal week 2. Weight gain was the same in both groups. Corrected parenteral amino acid intake at postnatal week 1 correlated directly with weight gain from birth to postnatal week 2 (P &lt; 0.03) in both groups.ConclusionsInfants with extremely low birth weight tolerated parenteral amino acid intake of approximately 4 g · kg−1 · d−1. Mild increases of mean serum urea nitrogen concentration and mean weight gain were associated with increased parenteral amino acid administration without significant acidosis.

Effects of Replacing Corn with Chinese Brown Rice on Growth Performance and Apparent Fecal Digestibility of Nutrients in Weanling Pigs

This experiment was conducted to study the effects of replacing corn with Chinese brown rice on performance and apparent fecal digestibility of nutrients in weanling pigs. Seventy-two cross-bred (Duroc×Landrace×Large White) weanling pigs, weighing an average of 7.38±0.06 kg, were randomly assigned to either a corn-soybean meal diet (treatment 1), a corn-brown rice- soybean meal diet (treatment 2) and a brown rice-soybean meal diet (treatment 3). The brown rice used in this experiment was husked from one kind of early, long grain, non-glutinous rice (ELGNR, indica rice). The growth performance of weanling pigs in the experiment was similar during weeks 1 and 2, but feed conversion ratio (FCR) was significantly better in treatment 2 during weeks 3 and 4. During week 2, only the digestibility of organic matter in treatments 2 and 3 was significantly higher than that in treatment 1. During week 4, the digestibility of gross energy, ether extract, organic matter and dry matter in brown rice treatment, especially in treatment 3, were significantly higher than in treatment 1. At the end of the experiment, the concentration of serum urea nitrogen of pigs in treatment 2 was lower than that in treatment 1 and 3 and no difference was found in serum glucose and phosphorus. It could be concluded from this experiment that replacing 50% of corn with brown rice in the corn-soybean meal diet caused no negative effects to weanling pig performance, and apparent fecal digestibility was unaffected. It is feasible to replace corn with brown rice in weanling pig diets in southern China. (Asian-Aust. J. Anim. Sci. 2002. Vol 15, No. 8 : 1191-1197)

Role of endogenous regucalcin in transgenic rats: suppression of kidney cortex cytosolic protein phosphatase activity and enhancement of heart muscle microsomal Ca2+-ATPase activity.

Rats were generated by pronuclear injection of the transgene with a cDNA construct encoding rat regucalcin that is a regulatory protein of Ca2+ signaling. Transgenic (TG) founders were fertile, transmitted the transgene at the expected frequency, and bred to homozygote. Western analysis of the cytosol prepared from the tissue of TG female rats (5-week-old) showed a remarkable expression of regucalcin (3.3 kDa) protein in the liver, kidney cortex, heart, lung, stomach, brain, spleen, muscle, colon, and duodenum. Regucalcin expression of TG male rats was seen in the liver, kidney cortex, heart, and lung. In wild-type (wt) male and female rats, regucalcin was mainly present in the liver and kidney cortex. Regucalcin inhibited protein phosphatase activity in rat kidney cortex cytosol and activated Ca2+-ATPase activity in rat heart muscle microsomes. The suppressive effect of regucalcin on protein phosphatase activity was significantly enhanced in the cytosol of kidney cortex of TG male and female rats as compared with those of wt rats. Likewise, heart muscle microsomal Ca2+-ATPase activity was significantly enhanced in TG rats. The changes in their enzyme's activities in TG rats were completely abolished in the presence of anti-regucalcin monoclonal antibody (100 ng/ml) in the enzyme reaction mixture. Moreover, the body weight of TG female rats was significantly lowered as compared with that of wt rats. Serum inorganic phosphorus concentration was significantly increased in TG male and female rats, while serum calcium, glucose, triglyceride, free cholesterol, albumin, and urea nitrogen concentrations were not significantly altered in TG rats. Regucalcin TG rats should be a useful model to define a regulatory role of endogenous regucalcin in the tissues in vivo.

C-myc antisense oligonucleotide treatment ameliorates murine ARPKD

Overexpression of c-myc is postulated to play a role in the pathogenesis of polycystic kidney disease (PKD). c-myc expression is increased in all rodent models of PKD that have been examined as well as in human ADPKD. To determine whether overexpression of renal c-myc contributes to renal cyst formation, C57BL/6J-cpk litters (an animal model of ARPKD) were treated with an antisense oligomer (ASO) to c-myc mRNA. Injections of 30 microg of a c-myc ASO were given to C57BL/6J-cpk litters on postnatal days 7-20. Control mice received either sham injections or injections of an equal amount of a scrambled ASO. At 20 days, kidney weight, body weight, serum urea nitrogen (SUN), hematocrit, and renal concentration of ASO were determined. In kidney, c-Myc and PCNA protein were assessed by immunoblotting and steady state levels of renal RNA for c-myc, EGF, SGP-2, and histone H4 were assessed by northern blot hybridization. c-Myc and PCNA proteins were localized by immunohistochemistry. Cystic mice treated with the c-myc ASO had a decreased relative kidney weight, improved renal function, and a reduced amount of cystic change compared with sham and scrambled ASO controls. The abnormal expression of several PKD related proteins and mRNAs were partially reversed by c-myc antisense treatment. c-myc staining appeared to be reduced in the noncystic tubules. Treatment with the c-myc ASO did not cause a reduction in hematocrit or total body weight indicating that the beneficial effects were not due to a generalized inhibition of cell proliferation in rapidly growing tissue. c-Myc appears to play a role in the cystogenesis of cpk-induced murine PKD and antisense targeting the overexpression of c-myc partially ameliorated the renal changes.

ANDROSTENEDIONE SUPPLEMENTATION AND POLYCYSTIC KIDNEY DISEASE

The purpose of this study was to investigate the effect of androst-4-ene-3,17-dione (ANDROSTENEDIONE) supplementation in an animal model of Autosomal Dominant Polycystic Kidney Disease (ADPKD). It is hypothesized that androstenedione, because it is only one enzymatic reaction from testosterone conversion, may be an anabolic agent capable of elevating serum testosterone above normal levels, and because of this, androstenedione may exacerbate the disease state of ADPKD. Two groups of female PKD rats and two groups of male PKD rats were used (n = 18 females; n = 18 males). One group of females were supplemented with androstenedione in chow (n = 9) while the female controls received chow only (n = 9). Male rats were grouped in the same fashion. Rats were observed for a six-week period, from age 4 - 10 weeks. At the end of the six-week period, rats were euthanized via decapitation for total blood volume. Male rats receiving androstenedione had increased serum estrone concentrations compared to controls (p < 0.02) and female rats had increased serum testosterone concentrations compared to controls (p < 0.03). All rats receiving androstenedione supplementation had higher serum estradiol concentrations than controls (p < 0.02). Serum creatinine was significantly affected by gender, genotype, or treatment but rats with PKD had significantly increased serum creatinine concentration. Urinary creatine was increased in controls (p < 0.01) and was greater in males than females (p < 0.03). Total protein was decreased in females compared with males (p < 0.002). Concentration of serum urea nitrogen was increased among males and polycystic animals (p < 0.001). Urinary urea nitrogen was decreased in control males (p < 0.03) and androstenedione-supplemented females. Total kidney weight was increased among male and polycystic animals (p < 0.05). These data suggest androstenedione supplementation may promote estrogenization among males and androgenization among females and thereby exert a limited protective effect on males with PKD while exacerbating effects of PKD in females. Supported by Texas Woman's University Human Nutrition Research

Collagen metabolism is markedly altered in the hypertrophic cartilage of growth plates from rats with growth impairment secondary to chronic renal failure.

Skeletal growth depends on growth plate cartilage activity, in which matrix synthesis by chondrocytes is one of the major processes contributing to the final length of a bone. On this basis, the present work was undertaken to ascertain if growth impairment secondary to chronic renal insufficiency is associated with disturbances of the extracellular matrix (ECM) of the growth plate. By combining stereological and in situ hybridization techniques, we examined the expression patterns of types II and X collagens and collagenase-3 in tibial growth plates of rats made uremic by subtotal nephrectomy (NX) in comparison with those of sham-operated rats fed ad libitum (SAL) and sham-operated rats pair-fed with NX (SPF). NX rats were severely uremic, as shown by markedly elevated serum concentrations of urea nitrogen, and growth retarded, as shown by significantly decreased longitudinal bone growth rates. NX rats showed disturbances in the normal pattern of chondrocyte differentiation and in the rates and degree of substitution of hypertrophic cartilage with bone, which resulted in accumulation of cartilage at the hypertrophic zone. These changes were associated with an overall decrease in the expression of types II and X collagens, which was especially marked in the abnormally extended zone of the hypertrophic cartilage. Unlike collagen, the expression of collagenase-3 was not disturbed severely. Electron microscopic analysis proved that changes in gene expression were coupled to alterations in the mineralization as well as in the collagen fibril architecture at the hypertrophic cartilage. Because the composition and structure of the ECM have a critical role in regulating the behavior of the growth plate chondrocytes, results obtained are consistent with the hypothesis that alteration of collagen metabolism in these cells could be a key process underlying growth retardation in uremia.

Cerebral edema in children with diabetic ketoacidosis.

Cerebral edema is the most frequent serious complication of diabetic ketoacidosis (DKA) in children, occurring in 1% to 5% of DKA episodes. The rates of mortality and permanent neurologic morbidity from this complication are high. The pathophysiologic mechanisms underlying DKA-related cerebral edema are unclear. A number of past and more recent studies have investigated biochemical and therapeutic risk factors for the development of cerebral edema. Recent studies have shown that a higher initial serum urea nitrogen concentration and lower initial partial pressure of carbon dioxide are associated with the development of cerebral edema. This and other information suggests that the pathophysiology of DKA-related cerebral edema may involve cerebral ischemia.