Influence of maternal protein restriction in primiparous heifers during mid- and/or late-gestation on meat quality and fatty acid profile of progeny.

The objective of this study was to evaluate the influence of metabolizable protein (MP) restriction in mid- and/or late-gestation on meat quality characteristics of progeny. Heifers were assigned to 2 levels of dietary protein (control [CON], 102% of MP requirements; or restricted [RES], 80% of MP requirements) at 2 stages of gestation (mid-gestation [MID] and late-gestation [LATE]) in a Balaam's Design crossover treatment structure resulting in 4 treatment combinations (CON-CON, CON-RES, RES-CON, RES-RES). A carryover effect of MID MP treatment on LATE CON indicated CON-CON steaks were more tender (P < .001) than RES CON. Mid-gestation restriction resulted in progeny with increased (P < .05) carcass water, soft tissue moisture, and decreased soft tissue fat percentage compared with progeny from dams receiving MID CON. Reduced maternal MP also differentially influenced the fatty acid profiles of progeny. Results suggest it is possible for progeny to overcome a moderate gestational MP restriction with minimal impacts on carcass composition or meat characteristics.

Effect of nursing-calf implant timing on growth performance and carcass characteristics.

The objective of this study was to compare pre- and postweaning growth performance, carcass characteristics, and meat quality attributes of calves that did not receive an implant or were implanted early or late in the nursing period. Crossbred steer calves ( = 135) were stratified by birth date and birth weight and randomly assigned to the following implant treatments: control (CON; no preweaning implant), 58 d (EARLY; 36 mg zeranol, administered at an average of 58 ± 13 d of age), and 121 d (LATE; 36 mg zeranol, administered at an average 121 ± 13 d of age). After weaning, steers were blocked by initial feed yard BW to 15 pens (5 pens/treatment and 9 steers/pen). All steers were implanted on d 21 after arrival at the feed yard and again on d 108 of finishing. Steer BW and ultrasound assessment of rib eye area (uREA), rib fat thickness (uRFT), and percent intramuscular fat (uIMF) were collected when implants were administered, at weaning, and on harvest day. Carcass measurements included HCW, rib eye area (REA), 12th-rib fat thickness (FT), and marbling score. Objective color (L*, a*, and b*) was recorded, and a 3.8-cm strip loin section was removed from both sides of each carcass and portioned into 2.54-cm steaks that were aged for 3 or 14 d for analysis of cook loss and Warner-Bratzler shear force (WBSF). The remaining portion of each sample was used for analysis of moisture and crude fat. Steer BW, ADG, and G:F did not differ among treatments ( > 0.05). Steers implanted in the EARLY treatment had a greater ( < 0.05) cumulative DMI than CON but were not different from steers implanted in the LATE treatment. Ultrasound REA and uRFT (averaged across all collection days) did not differ ( > 0.05); however, steers on the CON treatment had a greater ( ≤ 0.05) percent uIMF than EARLY implanted steers, whereas steers receiving the LATE implant were intermediate and not different from the other treatments. Hot carcass weight, REA, FT, USDA yield grade, marbling score, and objective color did not differ ( > 0.05) among treatments. The proportion of steers in each USDA yield and quality grade was similar ( > 0.05) among treatments, and no differences were detected for total carcass value or price per 45.4 kg (hundredweight; > 0.05). Treatment did not influence ( > 0.05) percent cook loss, crude fat, moisture, or WBSF. In conclusion, administering a nursing implant, regardless of timing, did not influence live performance, carcass characteristics, or meat quality of steers fed in this study.

The influence of maternal nutrition on expression of genes responsible for adipogenesis and myogenesis in the bovine fetus.

The objective of this study was to determine whether altered maternal energy supply during mid-gestation results in differences in muscle histology or genes regulating fetal adipose and muscle development. In total, 22 Angus cross-bred heifers (BW=527.73±8.3 kg) were assigned randomly to the three dietary treatments providing 146% (HIGH; n=7), 87% (INT; n=7) or 72% (LOW; n=8) of the energy requirements for heifers from day 85 to day 180 of gestation. Fetuses were removed via cesarean section at day 180 of gestation and longissimus muscle (LM) and subcutaneous fat were collected and prepared for analysis of gene expression. Samples from the LM and semitendinosus (ST) were evaluated for muscle fiber diameter, area and number. The right hind limb was dissected and analyzed to determine compositional analysis. Fetal growth and muscle histology characteristics of the LM and ST were similar among treatments. Preadipocyte factor-1 expression was up-regulated in fetal LM (P<0.05) of HIGH fetuses as compared with INT, whereas LOW fetuses showed increased CCAAT/enhancer-binding protein-ß (C/EBP-ß) expression in LM as compared with INT (P<0.05). Peroxisome proliferator-activated receptor γand C/EBP-α did not differ as a result of dietary treatment in LM or subcutaneous fat samples. There was a tendency for increased expression of fatty acid synthase in LM of LOW fetuses as compared with INT (P<0.10). Myogenin was more highly expressed (P<0.05) in LM of the LOW fetuses, whereas µ-calpain expression was increased in the HIGH treatment compared with INT. A tendency for increased expression of IGF-II was observed for both LOW and HIGH fetuses compared with INT (P<0.10). Expression of stearoyl-CoA desaturase, myoblast determination protein 1, myogenic factor 5, myogenic regulatory factor-4, m-calpain, calpastatin, IGF-I and myostatin was similar between treatments. Collectively, these results suggest that fetal growth characteristics are not affected by the level of maternal nutritional manipulation imposed in this study during mid-gestation. However, differences in expression of fetal genes regulating adipose and muscle tissue growth and development could lead to differences in postnatal composition and warrants further investigation.

The influence of maternal energy status during mid-gestation on beef offspring tenderness, muscle characteristics, and gene expression.

The objective of this study was to determine if maternal energy status during mid-gestation influences the expression of genes regulating muscle and fat development, and muscle characteristics that may impact meat tenderness. Cows grazed dormant, native range (Positive Energy Status [PES]) or were fed at 80% of maintenance energy requirements (Negative Energy Status [NES]) during mid-gestation. Steer offspring were harvested after 21 d in the feedlot (weaning subsample) or after 208 d in the feedlot (final subsample). Greater 21-d tenderness was observed in NES steers, resulting from reduced collagen content in longissimus lumborum steaks. In the semitendinosus, NES steers had greater soluble collagen, and down-regulated expression of MHC-IIA and TIMP-3 at weaning, while MHC-IIA expression was up-regulated in NES steers in the final harvest. Data show mid-gestational maternal energy status may impact offspring tenderness and collagen, but differences were not detected in expression of genes important in myogenesis and adipogenesis in muscle samples obtained from steers at weaning or slaughter.

Impact of supplemental protein source offered to primiparous heifers during gestation on II. Progeny performance and carcass characteristics.

A 3-yr study using primiparous crossbred beef heifers (n = 114) was conducted to determine the effects of protein supplement during late gestation on progeny performance and carcass characteristics. Pregnant heifers were stratified by heifer development system, initial BW, and AI service sire and placed in an individual feeding system. Heifers were offered meadow hay (8 to 11% CP) from early November to mid-February and provided no supplement (CON; n = 37), 0.83 kg/d (DM basis) of a dried distillers grains with solubles-based supplement (HI; n = 39), or 0.83 kg/d (DM basis) of a dried corn gluten feed-based supplement (LO; n = 38). Supplements were designed to be isonitrogenous (28% CP) and isocaloric but to differ in RUP with HI (59% RUP) having greater levels of RUP than LO (34% RUP). After the individual feeding period, heifers were placed in a drylot for calving. All heifers were bred using a fixed-timed AI protocol and pairs were moved to a commercial ranch in the Nebraska Sandhills for summer grazing. Calf weaning BW did not differ (P = 0.14) based on maternal diet. However, feedlot entry BW was greater (P = 0.03) for HI compared with CON calves. Average daily gain during the initial feedlot phase tended (P = 0.10) to be greatest for calves born to CON dams and lowest for calves born to LO dams. However, overall ADG was similar (P = 0.50) for the entire feedlot period. Residual feed intake during the reimplant and total feeding period was improved in calves born to supplemented dams in yr 2 and 3 compared with calves born to CON dams. There was no difference in final BW among treatments (P = 0.71). Hot carcass weight was similar (P = 0.72) among treatments; however, steers had greater (P < 0.01) HCW than heifers. Furthermore, percent empty body fat and 12th rib fat thickness were lowest (P = 0.05 and P = 0.04) for calves born to LO dams. Tenderness measured by Warner-Bratzler shear force was increased (P = 0.03) in longissimus samples from calves from CON dams compared to calves from LO dams. Similarly, crude fat levels tended to be greater (P = 0.07) for calves from CON dams compared with calves from LO dams. Based on these data, providing RUP supplements, similar to those used in this study, to primiparous heifers in late gestation consuming ad libitum grass hay resulted in increased initial feedlot BW for HI compared to CON calves, improved feed efficiency, and altered carcass characteristics in calves born to supplemented compared with CON dams.

The influence of maternal energy status during midgestation on beef offspring carcass characteristics and meat quality.

Research has suggested that maternal undernutrition may cause the development of a thrifty phenotype in the offspring, potentially resulting in greater adiposity and reduced muscle mass. These alterations in adipose and muscle development could have lasting impacts on offspring growth, carcass characteristics, and meat quality. However, limited research exists evaluating the impact of maternal energy status on these economically important traits of the offspring. Therefore, the objective of this study was to determine the influence of maternal energy status during midgestation on offspring carcass characteristics and meat quality. To alter maternal energy status, cows either grazed dormant, winter range (positive energy status [PES]) or were fed in a drylot at 80% of the energy requirements for BW maintenance (negative energy status [NES]) during a mean period of 102 ± 10.9 to 193 ± 10.9 d of gestation. Changes in BCS, BW, LM area (LMA), and 12th rib backfat were measured throughout midgestation. At the end of midgestation, cows in the NES group had a reduction (P ≤ 0.05) in BCS, BW, LMA, and 12th rib backfat when compared with PES dams. Cows and calves were managed similarly after midgestation through weaning and calves were managed and fed a common diet through the receiving, backgrounding, and finishing phases in the feedlot. Calves were harvested after 208 d in the feedlot, carcass characteristics were recorded, and strip loins were recovered for analysis of objective color and Warner-Bratzler shear force (WBSF). Maternal energy status had no influence on offspring HCW, dressing percent, LMA, percent KPH, marbling score, percent intramuscular fat, objective color, or WBSF (P > 0.10). Progeny of NES cows tended to have improvements in 12th rib backfat and USDA yield grade (P < 0.10). Greater ratio of marbling score to 12th rib fat thickness and ratio of percent intramuscular fat to 12th rib fat thickness (P < 0.05) were discovered in progeny from cows experiencing a NES during midgestation. These results suggest that maternal energy status during midgestation may impact fat deposition in intramuscular and subcutaneous fat depots without impacting muscle mass.

The influence of growth stage on carcass composition and factors associated with marbling development in beef cattle.

Subcutaneous fat and marbling both increase in beef cattle during the feeding phase but are antagonistic in regard to their contribution to beef carcass value. The objective of this study was to determine whether cellular factors associated with marbling development change with growth stage throughout the feeding period and whether they are correlated to marbling relative to carcass composition. Twenty-four steers of known origin with the cytosine and thymine (CT) leptin genotype were allotted to 3 harvest groups. Six steers per harvest group were harvested at the following predetermined points: 35 d on feed (early feeding period, EF), average live weight of 464 kg (middle feeding period, MF), and 1.17-cm 12th-rib subcutaneous fat thickness (late feeding period, LF). Longissmus muscle samples were collected within 30 min postmortem and snap frozen for real-time PCR and Western blot analysis of lipoprotein lipase, adenosine monophosphate-activated protein kinase α (AMPKα), stearoyl-coenzyme A desaturase (SCD), PPARγ, C/EBP-ß, and myostatin. Carcass data were recorded, and LM samples were collected and aged 2, 7, 14, and 21 d postmortem for Warner-Bratzler shear force determination. Carcass composition was estimated by dissection of the 9-10-11 rib section and subsequent proximate analysis of the soft tissue. Intramuscular fat content of the LM increased linearly throughout the feeding period, giving additional support to marbling as an early developing tissue. Expression of AMPKα was found to be downregulated, whereas SCD expression was upregulated in the LF group relative to the first 2 harvest groups. Additionally, SCD and PPARγ were downregulated in the EF group relative to the latter 2 harvest groups. These changes in gene expression resulted in a linear increase in only PPARγ protein abundance, whereas myostatin tended to increase quadratically. A correlation was found between intramuscular fat and PPARγ abundance. This gives further evidence of the importance of adipocyte hyperplasia in increasing marbling. Targeting and increasing PPARγ expression may serve as a mechanism to increase marbling deposition. Last, LF steaks were more tender than MF or EF steaks, indicating improved tenderness with increased days on feed.

Oral flecainide pharmacokinetics in patients with impaired renal function.

The pharmacokinetics of flecainide acetate were studied in 20 patients with varying degrees of renal impairment following a single oral dose. The patients were divided into two groups, on the basis of renal creatinine clearance (CLCR), for statistical and kinetic analysis. Patients with a CLCR between 4 and 41 mL/min/m2 were designated group 1 and those below 4 mL/min/m2 or unmeasurable because of lack of urine output were designated group 2. In both groups peak plasma flecainide concentrations, time to peak concentrations, and apparent volume of distribution (Vd) were similar to those reported in healthy subjects with normal renal function. The mean flecainide plasma elimination half-lives from both groups 1 and 2 were longer than those previously reported by several investigators in normal subjects. Nine patients in group 1 and seven patients in group 2 had half-lives within the range reported in healthy subjects. Therefore, CLCR alone is not a good predictor of plasma elimination half-life following a single oral dose of flecainide. Although renal clearance of flecainide is significantly reduced in end-stage renal disease (ESRD), total plasma clearance of flecainide (CLflec) was not reduced to the same degree, although there was a significant, modest correlation with CLCR. Less than 1% of the administered oral dose of flecainide was removed during hemodialysis. The relationship between dosage and plasma elimination half-life in patients with ESRD needs further study to evaluate possible dose-dependent kinetics.

Neurologic outcome and blood glucose levels during out-of-hospital cardiopulmonary resuscitation.

We examined the interrelations of outcome, time elapsed during cardiopulmonary resuscitation (CPR), and blood glucose levels drawn from 83 patients with out-of-hospital cardiac arrest. Levels rose significantly during CPR. Although slope and intercept of regression lines differed for those dying in the field and those admitted, regression lines were similar for those who awoke and never awoke after admission. These results suggest that the previously reported association between poor neurologic recovery and high blood glucose level on admission after cardiac arrest is best explained by prolonged CPR, leading to both higher rise of blood glucose and worse neurologic outcome.

Ketoconazole kinetics in chronic peritoneal dialysis.

The kinetics of oral ketoconazole in serum and peritoneal fluid were studied in six patients with renal failure receiving peritoneal dialysis. A dose of 400 mg ketoconazole resulted in a maximum blood concentration of 2.3 +/- 1.7 microgram/ml (mean +/- SD), which occurred 3.3 +/- 1.6 hours after dosing. The serum t1/2 was 2.4 +/- 0.8 hours. Peritoneal clearance values were less than 1 ml/min, and peritoneal penetration reached 3.4% of the serum concentration by 5 hours. Protein binding studies were also performed. Compared with healthy controls, patients receiving peritoneal dialysis have significantly less ketoconazole serum protein binding. Fifty to eighty percent of the drug is protein bound in the peritoneal fluid, and the unbound concentration is in the same range as that in the serum of healthy individuals with "therapeutic" total ketoconazole levels of 1 to 2 micrograms/ml.

Synergism at clinically attainable concentrations of aminoglycoside and beta-lactam antibiotics.

We evaluated the in vitro synergistic activity at clinically attainable concentrations of combinations of aminoglycoside and beta-lactam antibiotics against 30 gentamicin-resistant clinical isolates of gram-negative bacilli. All 56 pairs of 4 aminoglycosides and 14 beta-lactams were evaluated. Combinations with amikacin demonstrated inhibitory synergistic activity in 29% of the assays, as compared with 22% for netilmicin (P = 0.018), 17% for gentamicin (P less than 0.001), and 13% for tobramycin (P less than 0.001). Among the beta-lactams, combinations with cefoperazone, ceftriaxone, or cefpiramide (SM-1652) demonstrated inhibitory synergistic activity most often (39, 38, and 35% of the assays, respectively) and with ceforanide, cefsulodin, and imipenem least often (less than or equal to 8% each). The most active combination was amikacin and ceftriaxone, with which 67% of the assays demonstrated inhibitory synergism. Isolates with high-level resistance to either antibiotic in a combination were unlikely to be inhibited synergistically by the combination. Further, combinations generally demonstrated little synergistic activity against isolates highly susceptible to beta-lactams.

Cefonicid kinetics in subjects with normal and impaired renal function.

Cefonicid is a cephalosporin with a longer t1/2 than currently available cephalosporins. Cefonicid kinetics after an intravenous dose of 7.5 mg/kg were followed in four groups of subjects: group 1, four subjects with normal creatinine clearance (Clcr greater than 80 ml/min); group II, seven subjects with mild renal insufficiency (Clcr 50 to 80 ml/min); group III, five subjects with moderate to severe renal impairment (Clcr 8 to 49 ml/min); and group IV, five subjects with end-stage renal disease who were receiving maintenance hemodialysis (Clcr less than 8 ml/ml). Cefonicid volume of distribution ranged from 6.9% to 17.6% body weight but was not related to Clcr. Elimination t1/2 was 4.6 +/- 0.7 hr in group 1,6.0 +/- 2.7 hr in group II, 25.6 +/- 14.0 hr in group III, and 65.3 +/- 43.6 hr in group IV. There was a strong correlation between plasma cefonicid clearance and Clcr. Nonrenal clearance did not change with decreasing Clcr. Hemodialysis clearance calculated from plasma concentrations and recovery in dialysate was 2.5 +/- 0.9 ml/min. These kinetic parameters were used to formulate dosage regimens for patients with renal impairment.

Pharmacokinetics of ceftizoxime in patients undergoing continuous ambulatory peritoneal dialysis.

The pharmacokinetics of ceftizoxime were studied in 12 patients on continuous ambulatory peritoneal dialysis. After a 3-g intravenous dose, the steady-state volume of distribution was 0.23 +/- 0.05 liter kg-1, with an elimination half-life of 9.7 +/- 5.1 h. The peritoneal clearance of ceftizoxime (2.8 +/- 0.7 ml min-1) contributed modestly to the overall serum clearance of the drug (17.1 +/- 7.4 ml min-1) and was greater than the renal clearance (0.8 +/- 0.8 ml min-1). The peritoneal concentration rose to 91 +/- 29 micrograms ml-1 at 6 h, which was 0.61 +/- 0.17 of the serum concentration. A 3-g intravenous dose of ceftizoxime given every 48 h would result in adequate activity against most susceptible organisms, but more frequent dosing may be necessary for less susceptible organisms.

Gentamicin and tobramycin Kinetics.

Eighty-two hospitalized adult patients were randomized to treatment with gentamicin or tobramycin. Serum levels were compared to computer-derived mathematically predicted levels to evaluate predictability of gentamicin and tobramycin serum levels. When comparable dosages were used mean peak gentamicin levels (4.87 micrograms/ml) did not differ from those after tobramycin (4.31 micrograms/ml). Seventy-three percent of patients had peak levels after gentamicin greater than 4.0 micrograms/ml compared to 46% after tobramycin. Factors purported to influence predictability of aminoglycoside serum levels were examined. In 46 of 74 patients whose actual body weight was 10 to 35 kg less than estimated ideal body weight levels after both drugs were lower than predicted. Serum levels were also lower than predicted in 7 of 11 patients with ascites, 6 of 7 patients receiving carbenicillin therapy, and 17 of 29 patients who had pneumonia. Neither hematocrit nor temperature appeared to influence predictability of serum levels. A comparison of methods used to obtain computer-derived predicted levels showed that ideal body weight provided the most accurate prediction. Differences between predicted and measured levels were established when calculations were based on actual body weight (P = 0.009) or on surface area (P = 0.003 for peak and 0.023 for trough levels).

Effect of hemodialysis on the pharmacokinetics of theophylline in chronic renal failure.

We studied theophylline elimination in 8 patients with chronic renal failure to determine the effect of hemodialysis on the pharmacokinetics of theophylline. Each subject was studied twice, once on a nondialysis day and again during dialysis. Total body theophylline clearance on the nondialysis day was similar to that reported for patients with normal renal function (57.4 +/- 27.2 ml/kg/h). Hemodialysis accelerated theophylline elimination and shortened serum theophylline half-life in all patients (nondialysis t 1/2 = 7.3 h +/- 2.3 vs. dialysis t 1/2 = 2.7 +/- 0.9 h, p less than 0.01). Dialysis clearance averaged 59.7 +/- 16.4 ml/kg/h with a fraction of drug removed of 0.4 liters in 4 h. Guidelines for theophylline management during hemodialysis are suggested.

Sotalol kinetics in renal insufficiency.

Kinetics of sotalol, a beta adrenoceptor blocker, was studied in 20 patients with varying renal function. In subjects with creatinine clearance (Clcr) greater than or equal to 39 ml/min/m2, sotalol plasma clearance (x +/- SD) was 71 +/- 31 ml/min/m2, elimination half-life (t 1/2) was 8.1 +/- 3.4 hr, and renal clearance was 46 +/- 26 ml/min/m2. In patients with moderate renal impairment (Clcr = 8 to 38 ml/min/m2) elimination t 1/2 rose to 24.2 +/- 7.5 hr, and plasma clearance fell to 24 +/- 7 ml/min/m2. In patients receiving dialysis, elimination t 1/2 rose to 33.9 +/- 27.1 hr. Elimination t 1/2 during hemodialysis was 5.8 +/- 2.1 hr and was associated with a 56.7 +/- 21% reduction in plasma levels.

Randomized prospective evaluation of cimetidine and antacid control of gastric pH in the critically ill.

One hundred forty-four critically ill patients admitted to an intensive care setting were randomly assigned to cimetidine or antacid treatament groups. Gastric pH was monitored hourly. One hundred twenty-three (85%) patients demonstrated a fall in pH to less than 4 and were considered to require prophylaxis. Prophylaxis was considered adequate if the measured pH could then be maintained at greater than or equal to 4. Fifty-eight patients received antacids alone, the average requirement being 41 cc/hour. Sixty-five patients received cimetidine. Seventeen (26%) of the cimetidine prophylaxis patients failed to raise their pH and were than placed on hourly administration of antacid with successful elevations of pH to greater than or equal to 4 in all cases on an average supplementary dose of 53 cc/hour. Risk factors, including sepsis, hypotension, head injury, respiratory failure, degree of trauma, and age, were not statistically different in the two treated groups. Using these same criteria, responders to cimetidine could not be differentiated from nonresponders. All patients were protected from significant stress bleeding while on this study. Significant complications of either treatment were minimal. Antacids offered consistent protection against gastric acidity and were 100% effective. A routine schedule of 300 mg every six hours of cimetidine was effective in only 47% of patients, and the maximum dose of cimetidine was effective in only 74% of patients. Hourly measurement of intragastric pH is required for monitoring the response to prophylaxis of stress bleeding in severely ill patients.

Pharmacological and in vitro evaluation of cyclacillin: assessment as potential single-dose therapy for treatment of Neisseria gonorrhoeae infection.

The pharmacokinetic properties of cyclacillin administered as a 3.0-g oral dose, with and without progenecid, have been studied and correlated with in vitro activity of the drug against 109 isolates of Neisseria gonorrhoeae. By 8 h after dosage, levels of cyclacillin in serum declined below the minimal inhibitory concentration and the inferior antibacterial activity of cyclacillin (compared with that of amipicillin) suggest that cyclacillin is not a promising alternative to ampicillin for single-dose treatment of gonorrhea.