Effects of water restriction on feed intake, digestion, and energy utilization by mature female St. Croix sheep.

Eleven St. Croix ewes (46.9 ±â€¯1.59 kg BW and 3.6 ±â€¯0.67 yr age) were used in a crossover design to evaluate effects of restricted drinking water availability on intake of a 50% concentrate diet, digestion, and energy utilization. After 2 wk to determine ad libitum water consumption, there were two 4-wk periods, with measures in metabolism cages during wk 4. One treatment was water offered at the ad libitum level (CONT) and the other entailed a 25% reduction in wk 1 and 50% thereafter (REST). Although, some water was refused in wk 4, with intake of 2556 and 1707 g/day for CONT and REST, respectively (SEM=170.9). Digestibility of gross energy was greater (P = 0.034) for REST than for CONT (66.5 vs. 62.4%; SEM=1.16); however, because of a numerical difference (P = 0.448) in energy intake (15.79 and 14.66 MJ/day for CONT and REST, respectively; SEM=1.426 MJ/day), digested energy intake was similar between treatments (P = 0.870). Urinary energy was greater (P = 0.023) for CONT vs. REST (0.62 and 0.52 MJ/day; SEM=0.038) and methane energy did not differ (P = 0.213) between treatments (0.76 and 0.89 MJ/day; SEM=0.084), resulting in similar (P = 0.665) ME intake (8.50 and 8.01 MJ/day for CONT and REST, respectively; SEM=0.855). Both heat (8.60 and 8.33 MJ/day; SEM=0.437) and recovered energy (-0.10 and -0.30 MJ/day for CONT and REST, respectively; SEM=0.623) were similar between treatments (P ≥ 0.880). In conclusion, increased digestibility appears an important adaptive response to limited availability of drinking water.

MR Imaging Characteristics Associate with Tumor-Associated Macrophages in Glioblastoma and Provide an Improved Signature for Survival Prognostication.

BACKGROUND AND PURPOSE: In glioblastoma, tumor-associated macrophages have tumor-promoting properties. This study determined whether routine MR imaging features could predict molecular subtypes of glioblastoma that differ in the content of tumor-associated macrophages. MATERIALS AND METHODS: Seven internally derived MR imaging features were assessed in 180 patients, and 25 features from the Visually AcceSAble Rembrandt Images feature set were assessed in 164 patients. Glioblastomas were divided into subtypes based on the telomere maintenance mechanism: alternative lengthening of telomeres positive (ALT+) and negative (ALT-) and the content of tumor-associated macrophages (with [M+] or without [M-] a high content of macrophages). The 3 most frequent subtypes (ALT+/M-, ALT-/M+, and ALT-/M-) were correlated with MR imaging features and clinical parameters. The fourth group (ALT+/M+) did not have enough cases for correlation with MR imaging features. RESULTS: Tumors with a regular margin and those lacking a fungating margin, an expansive T1/FLAIR ratio, and reduced ependymal extension were more frequent in the subgroup of ALT+/M- (P < .05). Radiologic necrosis, lack of cystic component (by both criteria), and extensive peritumoral edema were more frequent in ALT-/M+ tumors (P < .05). Multivariate testing with a Cox regression analysis found the cystic imaging feature was additive to tumor subtype, and O6-methylguanine methyltransferase (MGMT) status to predict improved patient survival (P < .05). CONCLUSIONS: Glioblastomas with tumor-associated macrophages are associated with routine MR imaging features consistent with these tumors being more aggressive. Inclusion of cystic change with molecular subtypes and MGMT status provided a better estimate of survival.

Best management practices for newly weaned calves for improved health and well-being.

Morbidity and mortality in newly weaned calves resulting from bovine respiratory disease (BRD) continue to be the most significant problems facing the beef industry. Morbidity attributed to BRD accounts for approximately 75% of total feedlot morbidity. Several experiments have documented the economic impacts of BRD. Direct costs attributable to BRD include death loss, treatment and labor costs, and prevention costs, while indirect costs associated with BRD include decreased growth performance and feed efficiency, increased days on feed, and decreased carcass merit and market value. In recent years, cattle treated for BRD have returned $50 to $250 less per head at harvest than cattle never treated for BRD. Best management practices for newly weaned calves vary depending on a multitude of factors including: season of year calves are purchased, calf genetics, length of time in the marketing and transport channels, previous management and vaccination programs, and other factors. In general, calves purchased directly from a ranch have fewer health problems than calves purchased through auction markets. The longer a calf is in the marketing chain, the more likely health problems will be encountered. Calves that have spent several days in the marketing chain may develop clinical BRD before or very soon after arrival, whereas cattle with less time in the marketing chain may get sick later (2 to 4 wk), due to the length of time it takes for BRD to develop. On or before arrival, calves should be given a risk score (high, medium, or low) that relates to the quantity and magnitude of stress they have encountered and the probability they will develop BRD. High-risk calves typically will have been recently weaned, received no vaccinations, not been castrated or dehorned, been commingled, and moved through an auction market. Low-risk calves will often originate from a single source and will have gone through a preconditioning program that includes vaccination, castration, dehorning, weaning, and potentially feed bunk adaptation. Variation exists within risk category, so the preliminary assessment should be combined with visual observation on arrival as additional health assessments and feed intake information becomes available. Cattle managers should adjust management strategies based on risk category to meet the perceived needs of individual lots of cattle to improve the health and well-being of newly weaned calves.

Effect of bovine respiratory disease during the receiving period on steer finishing performance, efficiency, carcass characteristics, and lung scores.

Bovine respiratory disease (BRD) is responsible for the majority of morbidity, mortality, and production losses occurring in feedlots. This experiment evaluated the effects of BRD incidence on subsequent finishing performance, efficiency, carcass characteristics, and lung scores of steers. Crossbred steers (n = 516) were monitored daily for clinical signs of BRD (BRD attributed morbidity and mortality were 66.5 and 13.2%, respectively). A subset of calves (n = 174) were grouped by the number of times treated for BRD (BRDX) and randomly allocated to finishing pens. The BRDX experimental groups included never treated for BRD (0X; 8 pens) and treated 1 time (1X; 8 pens), 2 times (2X; 8 pens), or 3 or 4 times (3/4X; 8 pens). Arrival BW was not different among BRDX groups (P = 0.17); however, BRDX during the receiving period decreased performance, resulting in BW of 324, 316, 285, and 260 kg for 0X, 1X, 2X, and 3/4X, respectively, at the start of finishing (P < 0.001). Ultrasound estimates, BW, and visual appraisal were used to target a common body composition (average days on feed = 182). With increasing BRDX, days on feed increased linearly (P = 0.002), whereas HCW, DP, rib eye area, QG, and unconsolidated lungs decreased linearly (P ≤ 0.03). These results suggest that with additional days on feed, calves treated multiple times for BRD are able to reach similar compositional endpoints as their untreated cohorts; however, it may not be possible for these calves to reach the same QG and carcass yield.

Effect of timing of challenge following short-term natural exposure to bovine viral diarrhea virus type 1b on animal performance and immune response in beef steers.

Bovine respiratory disease (BRD) is the most common and economically detrimental disease of beef cattle during the postweaning period, causing the majority of morbidity and mortality in feedlots. The pathogenesis of this disease often includes an initial viral infection, which can predispose cattle to a secondary bacterial infection. The objective of this experiment was to determine the effects of timing of an intratracheal (MH) challenge relative to 72 h of natural exposure to bovine viral diarrhea virus (BVDV) type 1b persistently infected (PI) calves on performance, serum antibody production, total and differential white blood cell (WBC) count, rectal temperature, clinical severity score (CS), and haptoglobin (Hp). Steers ( = 24; 276 ± 31 kg initial BW) were randomly allocated to 1 of 3 treatments (8 steers/treatment) in a randomized complete block design. Treatments were steers not exposed to calves PI with BVDV 1b and not challenged with MH (CON), steers intratracheally challenged with MH 84 h after being exposed to calves PI with BVDV 1b for 72 h (LateCh), and steers intratracheally challenged with MH 12 h after being exposed to calves PI with BVDV 1b for 72 h (EarlyCh). Performance (ADG, DMI, and G:F) was decreased ( < 0.001) for both EarlyCh and LateCh from d 0 to 4. From d 5 to 17, LateCh appeared to compensate for this lost performance and demonstrated increased ADG ( = 0.01) and G:F ( = 0.01) compared with EarlyCh. Both EarlyCh and LateCh had decreased platelet counts ( < 0.001) compared with CON. Antibody concentrations of BVDV and MH were higher ( < 0.05) for both EarlyCh and LateCh compared with CON. Rectal temperature, CS, and Hp increased ( < 0.001) across time from h 4 to 48, h 4 to 36, and h 8 to 168, respectively. Within 24 h of MH challenge, WBC and neutrophil concentrations within the blood increased whereas lymphocyte concentrations decreased. The timing of BVDV exposure relative to a MH challenge appears to influence the CS and acute phase response associated with BRD. As typical beef cattle marketing channels allow for variation in the timing of respiratory pathogen exposure, understanding the physiological changes in morbid cattle will lead to improved management of BRD.

Effect of copper, manganese, and zinc supplementation on the performance, clinical signs, and mineral status of calves following exposure to bovine viral diarrhea virus type 1b and subsequent infection.

Research has indicated that trace mineral (TM) supplementation may alter immune function and reduce morbidity associated with bovine respiratory disease. The objective of this experiment was to determine the influence of dietary Cu, Mn, and Zn supplementation on the performance, clinical signs, and TM balance of calves following a bovine viral diarrhea virus (BVDV) and (MH) combination respiratory pathogen challenge. Steers ( = 16; 225 ± 20 kg BW) from a single ranch were processed, weaned, and randomly pairwise assigned to either the TM-supplemented (MIN) or the control (CON) experimental treatments. The MIN calves received an additional 150 mg of Cu, 130 mg of Mn, and 320 mg of Zn daily and the CON calves received the basal diet with no additional Cu, Mn, or Zn supplementation. The basal diet contained sufficient Mn and Zn but inadequate Cu based on published nutrient requirements. After 46 d on the experimental treatments, all calves were naturally exposed to a heifer persistently infected with BVDV type 1b for 4 d and then subsequently intratracheally challenged with MH. Data were analyzed using the GLIMMIX procedure of SAS with sampling time serving as a repeated measure and calf serving as the experimental unit. The respiratory challenge was validated via increased BVDV type 1b antibody concentrations, MH whole cell and leukotoxin antibody concentrations, rectal temperatures (TEMP), and subjective clinical severity scores (CS). Calf performance ( ≥ 0.48) was not affected by TM supplementation. Mineral supplementation also did not impact the CS or TEMP of calves ( ≥ 0.53). There was a treatment × time ( < 0.001) interaction observed for liver Cu concentrations. The concentrations of Cu, Mn, Zn, and Fe within the liver; Cu, Mn, and Zn within the muscle; and Cu, Zn, and Fe within the serum were all impacted by time ( ≤ 0.03). Calves receiving the MIN treatment had greater ( < 0.01) liver Cu and Mn concentrations compared with CON calves. In contrast, serum Cu and Fe concentrations were increased ( ≤ 0.05) in CON calves compared with MIN calves. Mineral supplementation did not impact TM concentrations within the muscle ( ≥ 0.38). The supplementation of Cu, Mn, and Zn can improve the Cu and Mn status within the liver and serum of calves in response to a BVDV and MH challenge. When Cu is supplemented to calves receiving a marginally Cu-deficient diet, Cu status within the body is significantly improved.

Feeding wet distillers grains plus solubles with and without a direct-fed microbial to determine performance, carcass characteristics, and fecal shedding of O157:H7 in feedlot heifers.

The inclusion of wet distillers grains plus solubles (WDGS) in feedlot diets has become a common practice in many regions of the United States due to the expanded production of byproducts and fluctuating corn prices related to ethanol production and other factors. In addition, societal concerns over the continued use of antimicrobials in agriculture production combined with an enhanced interest in disease and pathogen prevention in the food supply have led to an increased interest in use of direct-fed microbials (DFM) in growing and finishing cattle. Direct-fed microbials have been shown to improve ADG and feed efficiency, alter ruminal fermentation, and decrease fecal shedding of potential harmful pathogens in feedlot cattle in some experiments. The objective of this experiment was to evaluate the effects of WDGS inclusion with or without a DFM containing (1 × 10 cfu ∙ heifer ∙ d) combined with (1 × 10 cfu ∙ heifer ∙ d) on the performance, carcass characteristics, and O157:H7 shedding in feedlot heifers. In early August, 288 crossbred heifers (initial BW = 295 ± 28 kg) were assigned to 1 of 4 treatments (12 pens per treatment; 6 heifers per pen) in a randomized complete block design with a 2 × 2 factorial arrangement of treatments. Body weights and fecal grab samples were obtained at approximately 28-d intervals throughout the experiment. Across the feeding period, heifers fed 30% WDGS tended ( = 0.09) to have greater ADG and had greater carcass-adjusted ADG ( = 0.05) compared with heifers fed dry-rolled corn (DRC). Dry matter intake was not affected ( = 0.65) by diet, although carcass-adjusted G:F tended ( = 0.10) to be improved for heifers fed WDGS. Heifers fed 30% WDGS tended ( ≤ 0.10) to have greater fat thickness at the 12th rib, lower marbling scores, and higher yield grades. The inclusion of . combined with . in the diet had no effect ( > 0.10) on performance or carcass merit in the present experiment. The incidence of O157:H7 throughout the experiment was low, with only 18 positive samples across all sampling periods. Neither WDGS inclusion nor the inclusion of . combined with . in the diet had any effect ( > 0.10) on O157:H7 shedding in this experiment. Feeding 30% WDGS to feedlot heifers improved animal performance compared to the DRC-based control diet.

Evaluation of multiple ancillary therapies used in combination with an antimicrobial in newly received high-risk calves treated for bovine respiratory disease.

Ancillary therapy (ANC) is commonly provided in conjunction with an antimicrobial when treating calves for suspected bovine respiratory disease (BRD) in an attempt to improve the response to a suspected BRD challenge. The first experiment evaluated the effects of 3 ANC in combination with an antimicrobial in high-risk calves treated for BRD during a 56-d receiving period. Newly received crossbred steers (n = 516; initial BW = 217 ± 20 kg) were monitored by trained personnel for clinical signs of BRD. Calves that met antimicrobial treatment criteria (n = 320) were then randomly assigned to experimental ANC treatment (80 steers/experimental ANC treatment): intravenous flunixin meglumine injection (NSAID), intranasal viral vaccination (VACC), intramuscular vitamin C injection (VITC), or no ANC (NOAC). Animal served as the experimental unit for all variables except DMI and G:F (pen served as the experimental unit for DMI and G:F). Within calves treated 3 times for BRD, those receiving NOAC had lower (P < 0.01) clinical severity scores (severity scores ranged from 0 to 4 on the basis of observed clinical signs and severity) and heavier (P = 0.01) BW than those receiving NSAID, VACC, or VITC at the time of third treatment. Between the second and third BRD treatments, calves receiving NOAC had decreased (P < 0.01) daily BW loss (−0.13 kg ADG) compared with those receiving NSAID, VACC, or VITC (−1.30, −1.90, and −1.41 kg ADG, respectively). There were no differences in rectal temperature, combined mortalities and removals, or overall performance among the experimental ANC treatments. Overall, morbidity and mortality attributed to BRD across treatments were 66.5% and 13.2%, respectively. After the receiving period, a subset of calves (n = 126) were allocated to finishing pens to evaluate the effects ANC administration on finishing performance, carcass characteristics, and lung scores at harvest. Ultrasound estimates, BW, and visual appraisal were used to target a common physiological end point for each pen of calves. There were no differences among the experimental ANC observed during the finishing period (P ≥ 0.11). In summary, the use of NSAID, VACC, and VITC do not appear to positively impact clinical health and could potentially be detrimental to performance during the receiving period in high-risk calves receiving antimicrobial treatment for suspected BRD.

The effects of technology use in feedlot production systems on feedlot performance and carcass characteristics.

The objectives of this study were to examine the effects of feedlot production systems with and without the use of a ß-adrenergic agonist compared to an all-natural production program on feedlot performance and carcass characteristics. Crossbred beef steers ( = 336; initial BW = 379 ± 8 kg) were randomized to 1 of 3 treatments in a randomized complete block design (RCBD; 14 steers/pen; 8 pens/treatment). Treatments consisted of an all-natural treatment (NAT), a conventional treatment (CONV), and a conventional treatment with a ß-agonist (CONV-Z). All treatments were fed the same basal diet with NAT cattle receiving no growth promoting technologies. The CONV and CONV-Z cattle were implanted with 40 mg of estradiol and 200 mg of trenbolone acetate (TBA) on d 0 and were fed 33 and 9 mg/kg of monensin and tylosin daily, respectively. The CONV-Z cattle were fed zilpaterol hydrochloride (ZH) at 6.76 mg/kg (90% DM basis) for the last 20 days on feed (DOF) There was no effect of treatment on DMI ( = 0.83); however, CONV-Z steers gained 3.8% faster (1.64 vs. 1.58 kg/d; < 0.01) and were 5.3% more efficient (0.160 vs. 0.152; < 0.01) than CONV steers, and CONV steers gained 32.8% faster (1.58 vs. 1.19 kg/d; < 0.01) and were 26.7% more efficient (0.152 vs. 0.120; < 0.01) than NAT steers. There was a 35.7% improvement in estimated carcass gain (1.29 vs. 0.95 kg/d; < 0.01) and a 32.6% improvement in carcass efficiency (0.126 vs. 0.095; < 0.01) for CONV-Z steers compared to NAT steers. Hot carcass weight was increased by 8 kg for CONV-Z steers compared to CONV steers (394 vs. 386 kg; = 0.05) and 46 kg compared to NAT steers (394 vs. 348 kg; < 0.01). Longissimus muscle area was increased by 3.6 cm for CONV-Z steers compared to CONV steers (92.29 vs. 88.67 cm; = 0.02) and 12.1 cm for CONV-Z steers compared to NAT steers (92.29 vs. 80.16 cm; < 0.01), resulting in a 9.6% unit increase in USDA yield grade (YG) 1 (15.14 vs. 5.52%; < 0.05) and a 21.6% unit reduction in USDA YG 3 for CONV-Z steers compared to CONV steers (30.70 vs. 52.32%; < 0.05). The CONV-Z steers had a lower marbling score compared to the other treatments (432; 0.01), resulting in an 11.7% unit increase (20.70 vs. 9.03%; < 0.05) in USDA Select carcasses compared to CONV steers. The results of this experiment show that CONV-Z and CONV production results in a significant improvement in feedlot performance and USDA YG compared to NAT.

Cattle with increased severity of bovine respiratory disease complex exhibit decreased capacity to protect against histone cytotoxicity.

Bovine respiratory disease complex (BRDC) is the leading cause of morbidity and mortality in feedlot cattle. Significant inflammation and lesions are often observed in lungs of infected cattle. During acute inflammatory responses, histones contribute to mortality in rodents and humans and serum proteins can protect against histone-induced cytotoxicity. We hypothesized that cattle experiencing chronic or fatal cases of BRDC have reduced ability to protect against cytotoxic effects of histones. Serum samples were collected from 66 bull calves at the time of normal feedlot processing procedures. Animals were retrospectively assigned to groups consisting of calves never treated for BRDC (control [CONT]; n = 10), calves treated with antimicrobials once for BRDC (1T; n = 16), calves treated twice for BRDC (2T; n = 13), calves treated 3 times for BRDC (3T; n = 14), or calves treated 4 times for BRDC (4T; n = 13). Samples were also collected each time animals received antimicrobial treatment; animals within a group were further sorted by calves that recovered and calves that died to test histone cytotoxicity. Bovine kidney cells were cultured in duplicate in 96-well plates and exposed to 0 or 50 µg/mL of total histones for 18 h with 1% serum from each animal. Cell viability was assessed by the addition of resazurin for 6 h followed by fluorescent quantification. Fluorescent values from serum alone were subtracted from values obtained for histone treatment for each animal. Serum from CONT, 1T, and 2T at initial processing all exhibited a similar (P > 0.10) response to histone treatment with fluorescent values of -312 ± 557, -1,059 ± 441, and -975 ± 489, respectively. However, 3T and 4T demonstrated an impaired capacity (P < 0.05) to protect against histones (-2,778 ± 471 and -3,026 ± 489) at initial processing when compared to the other groups. When sorted by mortality within group, calves that were treated twice and recovered (-847 ± 331) demonstrated a greater (P < 0.05) protective capacity than calves that were treated twice and died (-2,264 ± 412), indicating that calves that contract BRDC and ultimately die might have reduced protective capacity against histone cytotoxicity. Results suggest that calves that require multiple treatments for BRDC have reduced ability to protect against cytotoxicity of histones. Understanding the primary mechanism responsible for protecting against histone cytotoxicity could lead to improved identification of animals susceptible to severe cases of BRDC, improved focus and use of available resources, or better treatments for severe cases of BRDC

Effects of beef production system on animal performance and carcass characteristics.

The objective of this study was to evaluate conventional (CONV) and natural (NAT) beef production systems from annual pasture through finishing through grazing. Beef steers (n=180, initial BW=250±19 kg) were assigned randomly to 2 treatments in the pasture phase. Steers were implanted with 40 mg of trenbolone acetate (TBA), 8 mg estradiol, and 29 mg tylosin tartrate (CONV), or received no implant (NAT). Steers on the 2 treatments grazed wheat or cereal rye for 109 d. Conventional steers had an 18.5% improvement in ADG (1.22 vs. 1.03 kg/d, P<0.01) and a heavier final BW (385 vs. 366 kg, P<0.01) compared with NAT steers. Following the pasture phase, steers (n=160 steers, 5 steers/pen, 8 pens/treatment) were assigned to a 2×2 factorial in the feedlot phase. Production system (NAT vs. CONV) was maintained from the pasture phase, and the second factor was 7 vs. 12% low-quality roughage (DM basis, LOW vs. HIGH). During finishing, CONV steers were given 120 mg of TBA and 24 mg estradiol at processing, fed monensin and tylosin, and fed zilpaterol hydrochloride for the last 20 d of the experiment. There were no program×roughage level interactions (P>0.07). The CONV steers ate 6.9% more feed (11.8 vs. 11.0 kg/d, P<0.01), gained 28.4% faster (1.90 vs. 1.48 kg/d, P<0.01), and were 24.2% more efficient (0.164 vs. 0.132, P<0.01) compared with NAT steers. The LOW steers had greater G:F (0.153 vs. 0.144, P<0.01) compared with HIGH steers. There was a 28.3% improvement in estimated carcass weight gain (1.36 vs. 1.06 kg/d), 18.6% improvement in carcass efficiency (0.115 vs. 0.097, P<0.01), and 21.6% improvement (1.52 vs. 1.25 Mcal/kg, P<0.01) in calculated dietary NEg for CONV compared with NAT steers. Hot carcass weight was increased by 62 kg (424 vs. 362 kg, P<0.01) and LM area was increased by 16.9 cm2 (100.9 vs. 84.0 cm2, P<0.01), decreasing USDA yield grade (YG, 3.09 vs. 3.54, P<0.01) for CONV steers compared with NAT steers. Natural steers had a greater percentage of carcasses in the upper 2/3 of USDA Choice grade (48.7 vs. 18.7%, P<0.01), a greater percentage of YG 4 and 5 carcasses (25.4 vs. 9.3%, P<0.01), and a greater percentage of abscessed livers (39.6 vs. 10.5%, P<0.01) compared with CONV steers. The results show that CONV production results in more rapid and efficient production that resulted in heavier carcasses with superior YG and desirable quality grades with both roughage levels.

Converting to gamma-radiation sterilization: an overview for medical device manufacturers.

Gamma radiation is becoming increasingly popular as a method of sterilizing disposable medical devices. The conversion from ethylene oxide sterilization to gamma radiation may involve redesigning products and packaging, and establishing a new method of sterilization. However, the conversion process can be regarded as an opportunity to enhance product design, improve processes, and reduce costs. In this article, the authors explain how conversion can be manageably achieved by providing a step-by-step conversion programme.

Neuropeptide Y potentiates excitation of supraoptic neurosecretory cells by noradrenaline.

The effects of neuropeptide Y (NPY) and noradrenaline (NA) on the activity of rat supraoptic nucleus (SON) neurosecretory cells were examined using perfused hypothalamic slices. Bath application of either NPY (10(-9)-10(-6) M) or NA (10(-6)-10(-3) M) excited SON cells, although only NA elicited consistent, dose-dependent effects. Application of NPY at a dose having virtually no direct effects (10(-8) M) produced a 5-fold increase in SON cell responsiveness to NA at the sub-maximal response dose of 10(-5) M, but did not alter the minimum concentration of NA required to excite SON cells or increase the maximal response elicited by higher NA concentrations. The effects of NA, alone or in combination with NPY, were abolished by alpha-adrenoreceptor blockade. These data suggest that NPY has only weak direct effects on neurosecretory cells, but may have important neuromodulatory actions, significantly enhancing the excitatory effects of NA.

Glucuronidation of propranolol by dog liver microsomes. Effects of enantiomeric inhibition and detergent treatment on stereoselectivity.

The diastereomeric glucuronides of (R)- and (S)-propranolol [(R)-PG and (S)-PG] formed by incubating the racemic drug with dog liver microsomes were separated and quantitated chromatographically. Conjugation occurred stereoselectively with 3- to 4-fold more (S)-PG than (R)-PG produced. The values for the apparent Km were 1.0 and 1.7 mM, and those of the Vmax were 6.4 and 25 nmol/min/mg protein for (R)- and (S)-propranolol, respectively. Stereoselectivity was lower in parallel incubations conducted with the separate enantiomers than in incubates with the racemic substrate. The S enantiomer was found to be a noncompetitive inhibitor of (R)-PG formation, with a Ki of 1.8 mM. (S)-PG did not inhibit (R)-PG formation when added to incubates and (R)-propranolol did not inhibit the formation of (S)-PG. The presence of sodium cholate and Brij 35 stimulated glucuronidation by 60 and 120%, respectively, but did not affect the stereoselectivity even at concentrations high enough to inhibit conjugation. On the contrary, Triton X-100 and Emulgen 911 were inhibitory and produced a decrease in stereoselectivity; the magnitude of these effects increased with increasing detergent concentration.

MMPI profiles of rheumatic fever adolescents and adults.

MMPI elevations for adolescent and adult groups (N = 162) who had experienced rheumatic fever (RF) were generally lower than Mayo Clinic norms, particularly on scales K, 1, 2, 3, and 6. Significant age effects on Scales F, 3, 4, 8, and 9 confirm previous findings that adolescent groups score higher on the MMPI. Contrary to expectation, patients who had not experienced carditis as part of their RF scored significantly higher than carditis patients on scales 2, 3, and 4. The results are discussed from a chronic disease perspective.

Plasma l-alpha-Acetylmethadol (LAAM) after acute and chronic administration.

l-alpha-Acetylmethadol (LAAM) was administered orally to two groups of subjects; one group received methadone, 50 mg/day, for three months previously and the other group were heroin addicts who had no prior exposure to methadone or LAAM. Plasma elimination curves for methadone, LAAM, and its metabolites, noracetylmethadol (N-LAAM) and dinoracetylmethadol (DN-LAAM), were determined after acute and chronic administration. The plasma decay curve for LAAM was biexpoenential (t1/2alpha = 6 hr; t1/2beta greater than 50 hr) following acute or chronic administration. Following chronic administration, N-LAAM and DN-LAAM plasma levels increased 5- to 10-fold. At this time, N-LAAM had a t1/2 of 31 hr and DN-LAAM had a t1/2 of greater than 100 hr. There appear to be at least two factors which determine the long duration of action of LAAM: metabolic conversion to active metabolites and tissue or plasma binding. Both methadone and LAAM may compete for plasma protein or tissue binding sites. The clinical implications of this potential drug-drug interaction are discussed.