Activation and re-expression of surface antigen in microglia following an epidural application of kainic acid in the rat brain. Following an epidural application of kainic acid over the sensorimotor cortex in rats, the ipsilateral hippocampus and the ventrobasal nuclear complex of the thalamus showed extensive neural degeneration. The neuronal death, either as a result of direct neurotoxic destruction or wallerian and retrograde degeneration, elicited a dramatic expression of immunoreactivity on numerous cells bearing the external morphology of microglia. Thus, with the monoclonal antibody OX-42, many amoeboid immunoreactive cells bearing stout processes were observed in the above-mentioned lesioned sites. The present electron microscopic immunocytochemical study confirmed that these OX-42 positive cells were activated microglia characterised by an abundant cytoplasm containing a variable number of lysosomes and phagosomes. The surfaces of these activated microglial cells were thrown into pseudopodial processes engaged in the phagocytosis of cellular debris. Immunoreactivity was also observed in these cells with the monoclonal antibodies OX-18 and OX-6, although in the latter the immunoreactive cells were fewer and less intensely stained. With OX-42, the corresponding areas on the contralateral side showed some widely scattered typical microglial cells bearing extremely fine processes. They were not stained with either OX-18 or OX-6. It was concluded from this study that neural degeneration induced the expression of CR3 receptors (marked by OX-42) and MHC encoded antigens (marked by OX-18 and OX-6) in microglia. The elevation of the former antigen was related to their active phagocytic activity. The latter, on the other hand, would facilitate the capability of interaction between the activated microglia and T lymphocytes in a possible immune response.


Magnetic resonance imaging of semicircular canals. The present paper reports the results of the first investigation of the semicircular canals in a living, small animal by means of high spatial resolution magnetic resonance imaging. This procedure is noninvasive and allows identification of the endolymphatic and perilymphatic spaces yielding a morphology quite consistent with direct anatomical examination.


Effects of alternative lamb production systems, maternal line, and culling strategy on flock age structure. The 5-yr attrition of 1/4 (n = 411) or 1/2 (n = 403) Finnsheep (Finn) ewes exposed to terminal sire breeds in either an accelerated or semi-intensive annual lambing system was recorded to test the effects of system and percentage Finn on flock age structure at equilibrium. Ewes were culled for discernible ailments and failure to lamb after two consecutive non-spring exposures in yr 3, 4, or 5 only. Additionally, four progressively more intensive culling strategies for nonconception were practiced in retrospect. Flock productivity (kilograms of lamb weaned per ewe maintained per year) at age structure equilibrium was estimated for all culling strategies. The majority of all systems (cull strategy x lambing system x percentage Finn combination) were composed of ewes less than or equal to 3 yr old. Replacement requirements ranged from 24 to 38% in the accelerated system and 22 to 26% in the annual system. Quarter-Finns yielded greater replacement needs and shorter productive lives in accelerated lambing but fewer replacement requirements and longer productive lives than 1/2 Finns in annual lambing. Replacement requirements greatly increased with culling intensity in accelerated lambing (up to 54% above original levels) but only slightly in annual lambing (up to 8% above original levels). Mean (reproductive) lifetime estimated from fitted Weibull survival curves ranged from 3.1 to 5.1 yr in accelerated lambing and 4.5 to 5.4 yr in annual lambing. Increased culling for non-lambing decreased productivity at flock age structure equilibrium in accelerated lambing but did not change productivity in annual lambing. Repeatability of ewe effects on conception was generally low. Overall, system, percentage Finn, and culling strategy interact to influence system productivity through flock age structure. Intensive culling for non-lambing and replacement with ewe lambs of equal genetic merit should not be practiced in accelerated lambing systems.


Influence of calving season and stocking rate on birth weight and weaning weight of Simmental-sired calves from Brahman-Hereford F1 dams. Braham-Hereford F1 dams have been used to evaluate the influence of grazing pressure on forage attributes and animal performance at the Texas A&M University Agricultural Research Center at Overton. Data for this study were compiled from 1,909 records of Simmental-sired calves born to Braham-Hereford F1 cows from 1975 to 1990. Birth weight and weaning weight were analyzed independently to estimate the influence of year, season of birth, dam age, weaning age, and sex of calf. The effect of stocking rate as represented by levels of forage availability on weaning weights and subsequent birth weights was measured. Within the fall and winter calving seasons, lactating dams grazing at a high stocking rate produced calves with the lowest subsequent birth weights. Lactating dams assigned to creep-fed treatments had calves with the heaviest subsequent birth weights. Although dams that were less than 3.5 yr of age had calves with the lightest birth weights, there was no apparent decline in birth weight of calves from dams 12 to 17 yr old. Year, sex of calf, age of dam, stocking rate, season of birth, age at weaning, and birth weight were significant factors affecting weaning weight (P less than .01). Fall-born calves grazing cool-season annual pastures were heavier at weaning (267.6 kg) than either winter- (252.0 kg) or spring-born calves (240.9 kg). A stocking rate x season-of-birth interaction was observed for birth weight and weaning weight (P less than .05). Differences in weaning weight from low- vs high-stocked pastures were greater for fall-born calves (61.6 kg) than for winter-born calves (48.7).(ABSTRACT TRUNCATED AT 250 WORDS)


Prediction of carcass characteristics by real-time ultrasound in barrows and gilts slaughtered at three weights. The carcass characteristics of 27 market barrows and 27 market gilts were evaluated at various times (n = 8) with real-time ultrasound (Aloka 210 DX) from approximately 20 kg until slaughter at three end points. The pigs were randomly assigned to slaughter weight groups of 91, 104.5, and 118 kg at weaning time. Correlations were determined over slaughter weight group and sex, and the accuracies of ultrasound measurements were also evaluated. The regressions of ultrasound 10th-rib fat and ultrasound longissimus muscle area on live weight were also developed. Correlations between actual and ultrasound-measured last-rib fat, 10th-rib fat, and longissimus muscle area were high (r = .91, .63, and .53, respectively; P less than .01). The accuracy of ultrasound longissimus muscle area prediction was lower for 118-kg pigs than for the two lighter groups, whereas the accuracy for prediction of last-rib fat was lower for 91-kg pigs than for the two heavier groups, as indicated by higher absolute differences (P less than .05). Last-rib fat and longissimus muscle area tended to be overestimated and 10th-rib fat tended to be underestimated by real-time ultrasound. Prediction of last-rib fat by ultrasound was more accurate for gilts than for barrows, as indicated by a lower absolute difference (P less than .05).


Correlated changes in reproductive components accompanying 10 generations of selection for improved sow productivity index. Reproductive components were compared between a line of sows selected (S) for improved sow productivity index (SPI = 6.5 x number born alive + adjusted 21-d litter weight) and sows from an unselected control (C) line. Generation 9 and 10, second-parity, Landrace sows were chosen from both the S (n = 35) and C (n = 33) line. Sows were slaughtered at a commercial slaughter plant at approximately 75 d of gestation and their reproductive tracts were recovered. Reproductive tracts were evaluated for uterine weight (UTWT), uterine horn length (UTLN), ovulation rate (OR), number of fully formed fetuses (NF), number of mummified fetuses (NM), percentage of fetal survival (FS = NF/OR), fetal space (FSPACE = UTLN/[NF + NM]), and fetal position, sex, and weight. Select-line sows had greater NF (P less than .10) and higher FS (P less than .10) than C-line sows. Select-line sows had longer (P less than .05), and heavier (P less than .01) uteri than C-line sows. However, uterine length adjusted for NF was not different between the two lines. Uterine weight adjusted for NF was greater in S-line sows (P less than .05). Select-line sows had greater total fetal weight (TFWT) (P less than .05) than did C-line sows. Female fetuses positioned between two male fetuses were lighter in weight than all other female fetuses (P less than .01). Male fetuses positioned between two female fetuses did not differ in weight from all other male fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)


Economic evaluation of heterosis and culling policies for lifetime productivity in Hereford, Angus, shorthorn, and crossbred cows. Experimental lifetime performance data obtained from 156 straightbred Hereford, Angus, and Shorthorn and 172 first-cross heifers were used to estimate heterosis for economic efficiency in a 100-cow herd at age equilibrium under three culling policies and at terminal ages from 6 to 12 yr. All nonpregnant heifers and cows greater than 9 yr of age were culled. The culling policy for removal of nonpregnant cows from second parity through 9 yr of age were 1) no culling, 2) after two consecutive years (actual), and 3) all (imposed). Efficiency was calculated as input cost per unit of output value. A 10-yr average was used for costs of replacement heifers, cow units, and the ratio of calf:cull cow prices (PR), plus higher and lower PR. Input included costs for both cow units and purchased replacements. Output value included both weaned calves and cull cows. Optimum terminal age was mainly a function of PR: 9 yr for average and high PR, but 6 through 9 yr when PR was low, regardless of culling policy or breed groups. Efficiency differences among culling policies were small for high or average PR, but more culling for infertility was beneficial when PR was low. Estimated reductions in unit costs of output value under any culling policy or terminal age were approximately 6% from crossbred cows plus another 6% from crossbred calves, or a total of 12% from specific three-breed crossing of these British breeds. Cost reductions would be somewhat less for rotation crossbreeding but greater for mating smaller crossbred cows with sires of superior growth-carcass breeds.


Effect of culling on selection response using phenotypic selection or best linear unbiased prediction of breeding values in small, closed herds of swine. Records from 7,200 separate closed herds with either 12 or 25 sows that were mated to either four or eight boars per year were simulated by computer. Effects of selection method, herd size, and contemporary group variability on average genetic change, genetic variance, and inbreeding over 10 yr of selection were analyzed for traits with heritabilities of .1, .3, and .6. Selection of replacement animals was on individual phenotype or BLUP of breeding value using a reduced animal model. For both of these selection methods, two culling schemes were imposed: 1) based only on involuntary culling because of losses due to conception rate and age and 2) when an available replacement animal was projected to be superior to an existing breeding animal in the herd in addition to the involuntary culling. The contemporary group standard deviation was set at either .1 or .5 of a phenotypic standard deviation. Selection with BLUP gave 72, 36, and 12% more genetic improvement for heritabilities of .1, .3, and .6, respectively, than selection on individual phenotype after 10 yr. However, inbreeding increased 20 to 52% more rapidly and there was a decrease in genetic variance. Culling based on Scheme 2 increased genetic improvement over Scheme 1 by about 75% with coincident increases in inbreeding level and decreases in genetic variance. The largest changes in inbreeding and genetic variance were associated with culling on BLUP. Culling when a superior animal was available with individual phenotype had little effect on inbreeding and genetic variance. Use of four boars rather than eight boars and 25 rather than 12 sows per herd increased genetic response. Use of four boars also increased inbreeding and decreased genetic variance. Genetic variance was higher in herds with 25 sows, but the size of the sow herd had little effect on inbreeding. Contemporary group variation influenced only the genetic response of individual phenotypic selection with culling.


An embryo transfer study of reciprocal cross differences in growth and carcass traits of Duroc and Landrace pigs. Reciprocal cross differences have been reported for growth rate and carcass traits in F1 pigs with the Duroc (D) as a parent breed. Such differences are synonymous with maternal effects if effects of sex linkage and genomic imprinting are negligible. In the present study, transfer of embryos (ET) to paternal breed recipients partitioned effects occurring at or before fertilization from postfertilization effects for growth and carcass traits in F1 D-Landrace (L) pigs. Fifteen boars sired 115 F1 litters, 49 produced by ET. Growth rate of 349 barrows and 361 gilts and carcass measurements on 256 barrows and 159 gilts were analyzed assuming mixed linear models with animal and litter as random effects. Contrasts among genotype (D x L, L x D)- treatment (ET, non-ET) means were tested. Reciprocal cross differences were not detected for growth rate or for carcass weight, length, average backfat thickness, estimated carcass lean, or lean per day of age. Reciprocal cross differences for 10th rib backfat thickness (BF) and longissimus muscle area (LMA) were detected only in barrows. The sexual dichotomy for reciprocal cross differences followed expectations for a Y-linked gene(s), consistent with the fact that reciprocal D-L crossbred barrows exhibited a paternal effect, with responses more like the sire breed than the dam breed. Barrows that were non-ET from D sires and L dams had 3.9 cm2 larger LMA and 5.8 mm less BF than barrows from L sires and D dams (P less than .001). Barrows from ET sired by D boars had 3.8 cm2 larger LMA than did barrows from ET sired by L boars (P less than .001), although no difference was detected for BF. Barrows sired by D boars reared in a D postfertilization environment (ET) had 6.2 cm2 greater LMA and 4.1 mm less BF (P less than .05) than barrows sired by L boars gestated and reared by D dams (non-ET). Barrows sired by D boars reared by L dams (non-ET) had 1.5 cm2 greater LMA and 2.3 mm less BF (P greater than .10) than barrows sired by L boars reared by L dams (ET). In conclusion, reciprocal cross differences detected for BF and LMA in barrows were established before or at fertilization and seemed to be Y-linked.


Sire x herd interactions for weaning weight in beef cattle. Weaning weight records of 44,357 Australian Angus calves produced by 1,020 sires in 90 herds were used to evaluate the importance of sire x herd interactions. Models fitted fixed effects of contemporary group (herd-year-date of weighing subclass), sex, calf age, and dam age and random effects of sire or of sire and sire x herd interaction using REML. Effects of standardizing the data, including sire relationships and including dam maternal breeding values (MBV) as a covariate were also investigated. Sire x herd interactions were found (P less than .05) in all cases and, in the most complete model, accounted for 3.3% of phenotypic variance. Across-herd heritabilities ranged from .19 to .28. Differential nonrandom mating among herds seemed to occur in the data. Significant sire x herd effects were observed for dam MBV, and adjustment for dam MBV yielded the smallest estimates of interaction variance and across-herd heritability. If sire x herd interactions were due only to genotype x environment interaction, within-herd heritabilities would range from .33 to .49. These estimates are larger than previously reported estimates. Thus, unreported environmental effects common to progeny of individual sires may also be involved in the observed interaction but could not be disentangled from true genotype x environment interaction effects using these data. Results of these analyses suggest that some accommodation of sire x herd interaction effects on weaning weight may be needed in beef cattle genetic evaluations, but a compelling case for development of herd-specific breeding value prediction cannot be made.


Effects of breed and retained heterosis on milk yield and 200-day weight in advanced generations of composite populations of beef cattle. Retained heterosis in F2 cows nursing F3 progeny was evaluated in 3-, 4-, and greater than or equal to 5-yr-old cows. Traits evaluated included milk yield at three stages of lactation and 200-d weight of progeny. Breed effects were evaluated in the nine parental breeds (Red Poll [R], Hereford [H], Angus [A], Limousin [L], Braunvieh [B], Pinzgauer [P], Gelbvieh [G], Simmental [S], and Charolais [C]) that contributed to the three composite populations (MARC I = 1/4 B, 1/4 C, 1/4 L, 1/8 H, 1/8 A; MARC II = 1/4 G, 1/4 S, 1/4 H, 1/4 A; and MARC III = 1/4 R, 1/4 P, 1/4 H, 1/4 A). Breed effects were significant for 12-h milk yield, estimated 200-d milk yield, and 200-d weight of progeny. Herefords were lowest (P less than .05) for 12-h milk yield and estimated 200-d milk yield, and Braunvieh produced significantly more milk than all breed groups except Pinzgauer and Simmental, for which the difference approached significance. The correlation among breed group means (nine parental breeds and three composites) for 12-h milk yield with 200-d weight of progeny was .91. When 200-d weight was adjusted to a common estimated 200-d milk yield, Hereford, Angus, Red Poll, and Limousin did not differ (P greater than .05); all were significantly lighter than Braunvieh, Pinzgauer, Gelbvieh, Simmental, and Charolais, which did not differ (P greater than .05) from each other.(ABSTRACT TRUNCATED AT 250 WORDS)


Genetic analyses of growth, real-time ultrasound, carcass, and pork quality traits in Duroc and Landrace pigs: I. Breed effects. Knowledge of breed effects on carcass and pork quality traits is required to develop commercial crossbreeding programs that emphasize product quality. A 2 x 2 diallel mating system involving Landrace and Duroc pigs was used to estimate individual heterosis, direct breed effects and reciprocal cross differences for post-weaning growth, real-time ultrasound, carcass, and pork quality traits. Data from 5,649 pigs and 960 carcasses representing 65 and 49 sires, respectively, were analyzed assuming animal models. Duroc-sired pigs had 2.1 cm shorter carcasses with 7.3 mm less 10th rib backfat (BF), 4.4 cm2 larger longissimus muscle area (LMA), yielded 2.1 kg more estimated fat standardized lean (FSL), gained 16.5 g more estimated lean per day of age (LDOA), and had 1.0% less water (PWAT) and 1.9% more intramuscular fat (IMF) in the longissimus muscle than did Landrace-sired pigs (P less than .01), adjusted to an off-farm live weight of 111 kg. Reciprocal cross differences were detected for BF, LMA, FSL, LDOA and for subjective marbling, firmness, and muscling scores (P less than .01). Durocsired F1 barrows had 6.3 mm less BF and 5.9 cm2 larger LMA, yielded 3.2 kg more FSL, gained 22.3 g more LDOA, and had less marbling in the longissimus muscle and heavier ham muscling than reciprocal cross barrows. Heterosis estimates (P less than .05) were 27.6 g/d (3.2%) for ADG, -5.8 d (-3.6%) for off-test age, 2.7 cm (3.4%) for carcass length, 1.5 kg (7.2%) for FSL, 14.7 g (5.7%) for LDOA, -.07 (-3.6%) for muscle color, -.5% (-13.2%) for IMF, and .3% (.3%) for PWAT. Breed effects were not detected (P greater than .10) for muscle pH, cooking loss, shear value, and water-holding capacity or for eating quality traits. Reciprocal cross differences suggest an advantage in using the Duroc as a terminal sire, but improved carcass composition and higher intramuscular fat did not seem to affect eating quality traits.


Genetic analyses of growth, real-time ultrasound, carcass, and pork quality traits in Duroc and Landrace pigs: II. Heritabilities and correlations. Knowledge of the genetic control of pork quality traits and relationships among pork quality, growth, and carcass characteristics is required for American swine populations. Data from a 2 x 2 diallel mating system involving Landrace and Duroc pigs were used to estimate heritabilities and genetic correlations among growth (ADG), real-time ultrasonic (US) measures of backfat thickness (BF) and longissimus muscle area (LMA), carcass characteristics, and various pork quality traits. Data were collected from 5,649 pigs, 960 carcasses, and 792 loin chops representing 65, 49, and 49 sires, respectively. Genetic parameters were estimated by REML assuming animal models. Heritability estimates were moderate to high for ADG, USBF, USLMA, carcass BF, and LMA, percentage of LM lipid (IMF), pork tenderness, and overall acceptability. Estimates were low to moderate for percentage of cooking loss, pH, shear force, percentage of LM water, water-holding capacity (WHC), pork flavor, and juiciness. Genetic correlations between US and carcass measures of BF and LMA indicate that selection based on US data will result in effective improvement in carcass characteristics. Selection for increased LMA and(or) decreased BF using US is, however, expected to result in decreased IMF and WHC, increased percentage of LM water and shear value, and in decreased juiciness, tenderness, and pork flavor. Average daily gain was favorably correlated with IMF and unfavorably correlated with shear force. Selection for increased ADG is expected to improve WHC but to decrease the percentage of LM water, with an associated decrease in juiciness. The results of this study suggest the feasibility of including meat quality in selection objectives to improve product quality. Favorable genetic correlations between IMF and eating quality traits suggest the possible merit of including IMF in the selection objective to improve, or restrict change in, pork eating quality.


Heterosis for lifetime production in Hereford, Angus, shorthorn, and crossbred cows. The effects of maternal heterosis and maternal and grandmaternal breed effects on cumulative lifetime number and weight of calves weaned per cow entering the breeding herd were evaluated for 172 reciprocal crossbred and 156 straightbred cows of the Hereford, Angus, and Shorthorn breeds. Cows born in 1960 and 1961 were developed and mated to calve first at 3 yr of age and those born in 1962 and 1963 at 2 yr of age. Performance under actual culling of cows nonpregnant in two consecutive years and imposed culling of any nonpregnant cows were analyzed. Reproductive rates and weaning weight per calf and per cow exposed increased (P less than .05) as cows advanced from 2 through 5 yr of age, peaked at ages 5 through 9 yr, and decreased from 9 through 12 yr. Effects of heterosis did not interact (P greater than .05) with age at first calving management. During the 12-yr span in the 2-yr-old first-calving management system, crossbred cows produced nearly one more calf than straightbred cows under the actual culling policy (.97 calves, P less than .10) and .82 more calves (P less than .10) if all nonpregnant cows were culled. Corresponding cumulative calf weight weaned was 272 kg (P less than .01), or 25% more, and 232 kg (P less than .01), or 30% more, for crossbred cows than for straightbred cows. The 12-yr cumulative calf weight weaned by straightbred Angus cows exceeded that of Shorthorn cows (P less than .05) and tended to be greater than that of Hereford cows.


Estimates of subprimal yields from beef carcasses as affected by USDA grades, subcutaneous fat trim level, and carcass sex class and type. One hundred beef carcasses were selected to represent the mix of cattle slaughtered across the United States. Selection criteria included breed type (60% British/continental European, 20% Bos indicus, and 20% dairy carcasses), sex class (beef and Bos indicus: 67% steers, 33% heifers; dairy: 100% steers), USDA quality grade (4% Prime, 53% Choice, and 43% Select), USDA yield grade (10% YG 1, 43% YG 2, 40% YG 3, and 7% YG 4), and carcass weight (steers: 272.2 to 385.6 kg, heifers: 226.8 to 340.2 kg). One side of each carcass was fabricated into boneless subprimals and minor cuts following Institutional Meat Purchase Specifications. After fabrication, subprimals were trimmed progressively of fat in .64-cm increments beginning with a maximum of 2.54 cm and ending with .64 cm. Linear regression models were developed for each individual cut, including fabrication byproduct items (bone, fat trim) to estimate the percentage yield of those cuts reported by USDA Market News. Strip loin, top sirloin butt, and gooseneck rounds from heifers tended to have a higher percentage yield at the same USDA yield grade than the same cuts from steers, possibly resulting from increased fat deposition on heifers. Percentage of fat trimmed from dairy steers was 2 to 3% lower than that from other sex-class/carcass types; however, due to increased percentage of bone and less muscle, dairy steers were lower-yielding. Fat trimmed from carcasses ranged from 7.9 to 15.6% as the maximum trim level decreased from 2.54 to .64 cm.


Beef carcass composition of slaughter cattle differing in frame size, muscle score, and external fatness. Commercial slaughter steers (n = 329) and heifers (n = 335) were selected to vary in slaughter frame size and muscle thickness score, as well as carcass adjusted 12th-rib fat thickness. After collection of USDA carcass grade data, one side of each carcass was fabricated into boneless primals, subprimals, and minor tissue components. Cuts were trimmed to 2.54, 1.27, and .64 cm of external fat, except for the knuckle, tri-tip, and tenderloin, which were trimmed of all fat. Forced four-variable regression equations were used to predict the percentage (chilled carcass weight basis) yield of boneless subprimals at the three fat trim levels as influenced by sex class, frame size, muscle score, and adjusted 12th-rib fat thickness. Independent variables that had the most influence on percentage yield of primals and boneless subprimals were adjusted 12th-rib fat thickness and sex class. Within the same phenotypic group, percentage of trimmable fat increased by 2.32% as 12th-rib fat thickness increased by .75 cm. Estimated percentage yield of the major subprimals from the loin and round tended to be higher or relatively equal for heifer carcasses at all trim levels compared with those subprimals from steer carcasses. Holding frame size, sex class, and fat thickness constant, there was a higher percentage yield of chuck roll, rib eye roll, and strip loin for carcasses from thick-muscled cattle than for those from average- and thin-muscled cattle. Frame size had little effect on percentage yield of boneless subprimals.


Meat composition and palatability of Holstein and beef steers as influenced by forage type and protein source. This experiment determined meat composition and palatability changes resulting from feeding Holstein (HOL) and crossbred beef (XB) steers diets containing corn silage (CS) or alfalfa haylage (AH) (forage type) and soybean meal (SM) or fish meal (FM) (protein source). Fifty-nine steers (30 HOL and 29 XB) were randomly assigned to diet combinations for a 2 x 2 x 2 (breed x forage x protein) factorial arrangement. Steers were fed to a fat-constant end point (fat depth over the longissimus muscle measured by ultrasound: 1.0 cm XB, .6 cm HOL). Proximate and fatty acid analysis and sensory evaluation were conducted on a rib eye roast and steaks, respectively, removed from the left side of each carcass at ribs 9 to 12. Proximate analysis of the longissimus muscle showed no significant difference (P greater than .05) in moisture, protein, or fat content due to breed, forage, or protein treatment. Forage type had no significant effect (P greater than .05) on amount of individual fatty acids found in longissimus muscle. However, total polyunsaturated fatty acids were higher (P greater than .05) for AH than for CS-fed animals. Longissimus muscle from steers fed FM had higher palmitoleic and lower stearic acid contents (both P less than .05) than longissimus muscle from animals fed SM. Muscle from HOL had higher palmitoleic and lower stearic acid contents than that from XB steers (both P less than .05). There was no significant interaction (P greater than .05) of breed with either diet treatment for individual fatty acid contents.(ABSTRACT TRUNCATED AT 250 WORDS)


Preparation of muscle samples for comparative electron microscopy. The interpretation of muscle structure by scanning electron microscopy (SEM) has not been consistent among various studies. Consequently, the literature is confusing with respect to the identity of T-tubules, transverse ridges, Z-disks, and intermyofibrillar connections. The objective of this research was to evaluate the effects of different methods of sample preparation and imaging on ultrastructural details of previously identified transverse structures and intermyofibrillar connections and to verify or disprove the commonality of these structures under different viewing conditions. Scanning electron microscopy coupled with a cold stage, SEM at room temperature, and transmission electron microscopy (TEM) of thin sections were most appropriate for exposing detail of inter- and intracellular structures and for measuring sarcomere length and spacing of intermyofibrillar connections. Scanning electron microscopy of samples mounted on a cold stage, fractured, and sublimed provided excellent images of meat and muscle ultrastructure and may be used in correlative microscopy. Sarcomere length and spacing between intermyofibrillar connections were similar among most specimen preparation techniques and were affected similarly by heat treatments. Results indicate that the regularly spaced transverse structures viewed by conventional SEM and the intermyofibrillar connections viewed by low-temperature SEM are Z-disks.


Effect of dietary fat and cholesterol level on growing pigs selected for three generations for high or low serum cholesterol at age 56 days. Thirty-six female pigs selected for three generations for high (HS, n = 18) and low (LS, n = 18) serum cholesterol at 56 d of age were used to test the hypothesis that the two populations would respond differently to a high-fat, high-cholesterol diet (HD) and a low-fat, low-cholesterol diet (LD). The animals were four-way crosses (Chester White x Landrace x Large White x Yorkshire). All pigs were fed a standard corn-soybean meal starter diet from weaning (at 4 wk) to 8 wk of age and a grower diet from 8 to 12 wk of age. Initial serum total cholesterol concentration at 12 wk of age was higher (P less than .05) in HS than in LS pigs (94.6 vs 76.9 mg/dL, respectively). The effect of genetic background persisted throughout the 13-wk experiment (25 wk of age); there was no interaction between diet and genetic background in serum total cholesterol (final concentrations were 114.3 mg/dL in HS-HD; 107.0 mg/dL in HS-LD; 105.9 mg/dL in LS-HD; and 89.7 mg/dL LS-LD). Trends over time revealed significant effects of diet (P less than .01) and genetic background (P less than .01) on serum total cholesterol. There was no effect of genetic background on high-density lipoprotein-cholesterol concentration; high-density lipoprotein-cholesterol as a percentage of serum total cholesterol was similar for all groups: 43% for HS-HD, 48% for HS-LD, 42% for LS-HD, and 45% for LS-LD.(ABSTRACT TRUNCATED AT 250 WORDS)


Efficacy of dietary D-alpha-tocopherol and DL-alpha-tocopheryl acetate for weanling pigs. A 2 x 3 factorial experiment in a randomized complete block design was conducted using a total of 180 weanling pigs in five replicates. The study evaluated the efficacy of two dietary vitamin E sources (D-alpha-tocopherol, DL-alpha-tocopheryl acetate) added at three dietary levels (16, 48, 96 IU/kg) during a 35-d postweaning trial. Pigs within each treatment were fed two similarly fortified vitamin E diets in sequence; the first contained 40% milk products and was fed to 14 d, and the second contained 20% milk product and 5% fat and was provided from 15 to 35 d postweaning. Five pigs per pen per replicate were bled weekly for serum analysis of alpha-tocopherol, Se, cholesterol, triglyceride, and glutathione peroxidase (GSH-Px) activity. At the end of the trial, one pig per pen was randomly selected and killed with liver, loin, lung, and heart excised and frozen for tocopherol analysis. Postweaning gains, feed intakes, and efficiencies were similar between the two vitamin E sources and at the various dietary levels. Serum tocopherol concentrations were consistently higher when D-alpha-tocopherol was provided. Vitamin E sources and levels had no effect nor did they influence weekly serum Se, cholesterol, or triglyceride concentrations or GSH-Px activity. A serum and tissue interaction (P less than .05) response occurred between dietary vitamin E source x level with alpha-tocopherol concentrations increasing linearly (P less than .01) as dietary vitamin E level increased, but at a higher rate when D-alpha-tocopherol than when DL-alpha-tocopheryl acetate as fed.(ABSTRACT TRUNCATED AT 250 WORDS)


Digestible tryptophan requirements of starting, growing, and finishing pigs. Seven hundred eight crossbred pigs were used in growth and digestion trials to determine the digestible tryptophan (Trp) requirement of starting (6 to 16 kg), growing (22 to 50 kg), and finishing (55 to 97 kg) pigs. Each growth trial evaluated a corn-fish meal-corn gluten meal basal diet, the basal diet with five incremental additions of L-Trp, and a control corn-soybean meal diet. The tryptophan content of the six incremental diets ranged from .13 to .255% for starting pigs, .08 to .18% for growing pigs, and .063 to .163% for finishing pigs. Lysine contents of basal diets were 1.38, .90, and .72% for starting, growing, and finishing diets, respectively. In all trials, ADG, ADFI, and gain/feed increased (P less than .001) linearly and quadratically as dietary Trp increased. Broken-line regression analyses determined the total dietary Trp requirements needed to optimize performance to be .19, .13, and .09% (as-fed basis) for starting, growing, and finishing pigs, respectively. These concentrations equated to Trp intakes of .96, 2.18, and 2.88 g/d. A digestion trial using growing pigs (29 kg initially) determined the apparent ileal digestibility of Trp in the basal starting and growing diets to be 72 and 70%, respectively; a similar trial with finishing pigs (55 kg initially) found 59% Trp digestibility for the basal finishing diet. Mean digestibility of L-Trp was 97%. Based on these values and the total Trp requirements given above, the digestible Trp requirements are .15, .10, and .06% for starting, growing, and finishing pigs, respectively.


Effect of consuming fungus-infected and fungus-free tall fescue and ergotamine tartrate on selected physiological variables of cattle in environmentally controlled conditions. Two experiments were conducted to determine the physiological responses of consuming a fungus-free (FF) or fungus-infected (INF) tall fescue diet (Exp. 1) or the FF diet plus ergotamine tartrate at 30 ppm (FF/ET, Exp. 2) in a thermoneutral (21 degrees C) or heat-stressed environment (32 degrees C, dry bulb; 10 degrees C dew point). Treatment periods lasted 28 d after a 10-d adaptation period. Experiment 1 was replicated three times, and Exp. 2 was replicated twice, with eight Holstein steers in each replicate (mean BW = 185 kg). Feed intake (FI), rectal temperature (RT), and respiration rate (RR) were recorded daily, and heart rate (HR) and infrared temperatures at the ear canal (ECT), ear tip (ETT), pastern (PT), coronary band (CBT), and tail tip (TTT) were recorded weekly. Consumption of INF and FF/ET compared with FF diets decreased (P less than .10) FI, HR, ECT, PT, CBT, and TTT and elevated (P less than .10) RT and RR by 2.8, 2.77 kg/d; 17, 23 beats/min; .8, 1.1 degrees C; .9, 1.1 degrees C; .8, .9 degrees C; 1.1, 2.6 degrees C; .3, .5 degrees C; and 8, 8 breaths/min; respectively. Ear-tip temperature was reduced (P less than .10) 1.6 degrees C by consumption of INF but not by consumption of FF/ET. Reduction of peripheral temperatures is indicative of reduced blood flow to peripheral areas as a result of vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of dietary cysteine supplements on canola meal toxicity and altered hepatic glutathione metabolism in the rat. Experiments were conducted to determine the effects of feeding canola meal (Brassica campestris and Brassica napus) on the rat hepatic glutathione detoxification system and whether dietary cysteine supplements might modify such effects. Rats were fed test diets for 14 d. Body weight change, feed consumption, hepatic glutathione concentration, and hepatic glutathione-S-transferase (GSH-S-T) activities were determined. Weight gain was decreased when canola meal was fed, whereas hepatic glutathione concentrations increased, as did hepatic GSH-S-T activity. All effects correlated with total glucosinolate concentration in the canola meal. Dietary cysteine supplements, however, did not influence the growth reduction and increased hepatic glutathione concentrations caused by feeding canola meal. Supplemental cysteine prevented the elevation in hepatic GSH-S-T activity. The elevation in hepatic glutathione concentration caused by canola meals was not an overcompensation caused by an initial depletion and therefore reflected a general hepatotoxicity. Feeding supplemental cysteine increased hepatic glutathione levels at early time intervals and delayed the induction of GSH-S-T caused by canola meal toxicity. There was no beneficial effect of supplemental dietary cysteine in overcoming the toxicity of high levels of canola meal, but supplemental cysteine did modify the canola meal-induced changes in hepatic glutathione metabolism.


Progesterone production by cultured luteal cells in the presence of bovine low- and high-density lipoproteins purified by heparin affinity chromatography. The objectives of this study were to separate plasma lipoprotein particles based on the presence (low-density lipoproteins; LDL) or absence of apolipoprotein B (high-density lipoproteins; HDL) and to compare the abilities of bovine LDL and HDL to stimulate progesterone production by bovine luteal cells in culture. Plasma lipoproteins were isolated by ultracentrifugation and separated into LDL and HDL by heparin affinity chromatography. Luteal cultures were treated with LDL or HDL cholesterol for 48 h on d 3 of the culture (d 0 = day of dissociation). Progesterone production by luteal cells increased in a dose-dependent manner with increasing concentrations of either LDL or HDL cholesterol. There were no differences in the ability of LDL or HDL cholesterol to stimulate luteal cells to produce progesterone. Because LDL and HDL were equally potent, and experiment was designed to investigate the ability of modified LDL or reconstituted particles without apolipoproteins to stimulate progesterone production. Stimulation of luteal cell progesterone production by lysine-modified LDL was 70% of unmodified LDL. Progesterone production in the presence of phosphatidylcholine liposomes or BSA containing cholesterol was 50 and 108% of that obtained with HDL or LDL. Evidence indicated that apolipoprotein-free particles that contained free cholesterol but not cholesterol esters stimulated luteal cells to produce progesterone.


Alteration of energy metabolism of calves fed below maintenance during 6 to 14 days of age. A study was conducted with seven groups of five to six Holstein-Friesian male calves to evaluate the effect of feeding level during 6 to 14 d of age on energy metabolism of unadapted young calves. Calves were transported at 2 to 3 d of age to their new environment. At 6 d of age measurements of heat production (HP) and ME intake started and continued over a period of 8 d. Calves were fed below (four groups) or near (three groups) the maintenance requirement (19 or 30 g of milk replacer powder.kg-.75.d-1). In contrast to ME intake, HP decreased throughout the experimental period. This decrease was larger at the low than at the high feeding level (3.1 vs .9 kcal.kg-.75.d-2; P less than .001). The relationship between HP and ME intake was estimated as HP = 91 + .318 x ME intake (kilocalories.kilogram-.75.day-1). The decrease in HP, together with the constant ME intake with time, resulted in a time-dependent relationship between HP and ME intake. Estimated basal metabolic rate and efficiency of ME utilization below maintenance decreased with time, whereas the maintenance requirement remained virtually unchanged (134 kcal.kg-.75.d-1). The influence of feeding level on energy metabolism in young calves increased with time. For at least 12 d after transportation the energy metabolism of young calves had not reached steady-state levels.


Cattle blood plasma and red blood cell alpha-tocopherol levels in response to different chemical forms and routes of administration of vitamin E. The chemical form and site of administration of vitamin E were assessed in cattle by measuring area under the time curve alpha-tocopherol levels in plasma and red blood cells (RBC). In Exp. 1, four groups of Holstein calves, 4 to 6 d old, received daily one of the following forms equivalent to 228 mg of alpha-tocopherol: D-alpha-tocopheryl acetate (DTA); DL-alpha-tocopheryl acetate (DLTA); D-alpha-tocopheryl polyethylene glycol 1,000 succinate (TPGS); and an experimental blend (EB) containing DTA and TPGS. A control group received no supplement. Temporal alpha-tocopherol responses were determined in blood samples collected for 35 d. Relative to controls whose plasma and RBC alpha-tocopherol levels remained unchanged, all supplementation increased (P less than .05) alpha-tocopherol levels in plasma and RBC in calves; the highest levels occurred in those that received either DTA or EB. In a second experiment, five Hereford steers with ruminal and duodenal cannulas were used in a crossover design to determine whether site of vitamin E administration affected plasma alpha-tocopherol levels. A single dose of 810 mg of DTA was placed daily into the rumen, and the same amount divided into five equal doses was given (into the duodenum) during a 12-h period. Plasma alpha-tocopherol levels were higher (P less than .05) when steers were ruminally dosed than when they were dosed duodenally. The results suggest that the alpha-tocopherol concentration of plasma and red blood cells in cattle depends on both the chemical form and on the site of administration.


Digestion, feed intake, and live weight gain by cattle consuming bermudagrass hay supplemented with whey. Three experiments were conducted with cattle consuming bermudagrass hay to determine whether low-level supplements of whey alone, corn alone, or whey plus corn affect feed intake, digestion, and(or) BW gain. Six ruminally and duodenally cannulated beef cows (574 kg), used in a Latin-square trial (Exp. 1), were fed bermudagrass hay without supplementation (control) or with 2.8% whey (low whey, LW), 5.6% whey (high whey, HW), 17.4% ground corn (C), 2.8% whey plus 14.9% corn (C-LW), or 5.6% whey plus 12.4% corn (C-HW). Supplementing with whey and(or) corn increased ruminal butyrate (8.8, 9.4, 10.0, 9.6, 10.5, and 11.0 mol/100 mol of total VFA for control, LW, HW, C, C-LW, and C-HW, respectively; SE = .20). Supplements did not affect microbial N flow at the duodenum. Six Holstein steer calves (158 kg) in a Latin square (Exp. 2) consumed bermudagrass hay ad libitum alone (control) or with .075 or .15% BW whey (LW and HW, respectively), .5% BW ground corn (C), or corn-whey mixes made by substituting whey for corn (C-LW and C-HW). Substituting .15% BW of whey for corn increased (P less than .05) total OM intake slightly (3.99, 3.84, 3.75, 4.11, 4.28, and 4.47 kg for control, LW, HW, C, C-LW, and C-HW, respectively; SE = .10). In an 84-d randomized block experiment (Exp. 3), 96 beef calves (194 kg) consumed (ad libitum) low-quality bermudagrass hay alone or with C, LW, HW, C-LW, or C-HW supplements.(ABSTRACT TRUNCATED AT 250 WORDS)


Bioavailability of vitamin E compounds in lambs. A study was carried out to assess the bioavailabilities of several forms of vitamin E in lambs. A total of 40 lambs was allotted to eight dietary groups of five each and supplemented or not daily for 60 d with equimolar amounts of different vitamin E compounds as follows: 1) control, no supplemental vitamin E, 2) DL-alpha-tocopheryl acetate, 3) D-alpha-tocopheryl acetate, 4), D-alpha-tocopheryl succinate, 5) D-alpha-tocopheryl polyethylene glycol 1,000 succinate (TPGS), 6) DL-alpha-tocopheryl nicotinate, 7) DL-alpha-tocopheryl nicotinate+ TPGS, or 8) D-alpha-tocopheryl acetate + TPGS. During these 60 d, serum alpha-tocopherol concentrations in the control lambs remained constant and lower (P less than .05) than in lambs that received all treatments. Various indices of bioavailability, including Cmax-C(i) (concentration maximum-concentration initial), Ct-C(i) (concentration terminal-concentration initial), areas under the serum concentrations profiles, and pooled increment were higher (P less than .05) with D-alpha-tocopheryl acetate+ TPGS than in the other groups, suggesting a synergism between these forms. No such effect was observed between nicotinate and TPGS. For the TPGS, a water-soluble form of vitamin E, the indices of bioavailability were lower (P less than .05) than for the other groups. D-alpha-tocopheryl acetate resulted in a bioavailability that outranked all the other forms of vitamin E, except those of D-alpha-tocopheryl acetate + TPGS. A slightly higher bioavailability index was observed for D-alpha-tocopheryl succinate than for DL-alpha-tocopheryl nicotinate.(ABSTRACT TRUNCATED AT 250 WORDS)


Serum alpha-tocopherol concentration in sheep after intramuscular injection of DL-alpha-tocopherol. Forty-three crossbred wethers weighing 35 to 60 kg were used to investigate the effect of a single i.m. injection of DL-alpha-tocopherol (DL-alpha-ol). Animals were offered 1 kg/d of a basal diet containing 25 ppm of vitamin E. Lambs were randomly assigned to one of five DL-alpha-ol injection treatments as follows: 1) control (placebo, 0 IU), 2) 125 IU, 3) 250 IU, 4) 500 IU, or 5) 1,000 IU. Blood samples were taken via jugular venipuncture on d 1 before treatment administration and thereafter at designated intervals up to 360 h postinjection. The i.m. injections of DL-alpha-ol irrespective of dose increased serum alpha-tocopherol. Results showed a dose x time interaction (P less than .0001) across all treatments. Serum alpha-tocopherol increased rapidly to maximum concentration during the first 8 to 12 h for all non-zero treatments, followed by a rapid decline to pretreatment values. The mean serum alpha-tocopherol concentration at 0 h was .69 microgram/mL. Estimated peak serum alpha-tocopherol concentrations +/- SE were 6.68 +/- 1.04, 9.62 +/- 1.04, 21.66 +/- 2.37, and 50.75 +/- 7.05 micrograms/mL for Treatments 2 through 5, respectively. Results showed a quadratic dose effect (P less than .0003) on maximum response with apparently no effect on time taken to reach this peak. There was also a quadratic dose effect (P less than .0001) on the area under the concentration-time curve. The time taken for serum alpha-tocopherol to return to pretreatment levels increased with dose (56, 64, 67, and 74 h, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)


alpha-Tocopherol concentrations in serum and tissues of sheep fed different sources of vitamin E. Thirty-five crossbred wethers were used to determine the concentrations of alpha-tocopherol in serum and tissues after oral supplementation of six different vitamin E product forms. Five wethers were assigned to each of the following treatments: 1) control, no supplemental vitamin E (C), 2) emulsifiable DL-alpha-tocopheryl acetate-dry (Rovimix E-50% SD), 3) nonemulsifiable DL-alpha-tocopheryl acetate-dry (Rovimix E-50% Ads), 4) emulsifiable DL-alpha-tocopheryl acetate-liquid (Rovimix E-40% Dispersible Liquid Concentrate [DLC]); 5) emulsifiable DL-alpha-tocopherol-liquid (Hoffmann-La Roche, E-40% DLC alcohol), 6) micellized DL-alpha-tocopheryl acetate-liquid (Bioglan, Inc., E-20%); and 7) micellized DL-alpha-tocopherol-liquid (Bioglan, Inc., E-20%). Animals were supplemented daily with 1,000 IU of their respective vitamin E sources for 56 d. Blood samples were collected daily from d 0 to 7 and weekly until d 56. Animals were subsequently killed by exsanguination after stunning and eight different tissues were collected for alpha-tocopherol analysis. There were effects of day, treatment, and day x treatment interaction on serum alpha-tocopherol. All supplemented groups were higher in serum alpha-tocopherol concentration than were the C wethers. The emulsifiable vitamin E alcohol liquid product form (Treatment 5) yielded higher (P less than .01) serum alpha-tocopherol concentration than the emulsifiable acetate liquid product (Treatment 4). Sheep on Treatment 5 reached maximum concentration on d 1, sheep on Treatment 6 on d 2, and the sheep on the remaining Treatments by d 3. Blood sera alpha-tocopherol concentrations stabilized by d 6 in all supplemented groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Combinations of rendered protein meals for growing calves. Complementary responses between rendered protein meals were investigated in this study. In a preliminary trial using 12 mature wethers in two replications, there was no difference (P greater than .20) in N digestibility between meat and bone meal (MBM; 96.7%), feather meal (FTH; 89.8%), and soybean meal (SBM; 98.7%). In a 112-d growth trial, individually fed calves (n = 120; 230 kg) received graded levels of FTH, MBM, 50:50 MBM-FTH (CP basis), or SBM with or without tryptophan (Trp) supplementation. Additions of Trp increased plasma Trp levels (P less than .05) but failed to improve efficiency of protein utilization (P greater than .35). Pooled results showed that this efficiency was greater (P less than .05) for FTH (1.47) than for MBM (1.04), FTH:MBM (.80), or SBM (.66). A trial was conducted to determine whether Trp addition reduces growth response to FTH:MBM (50:50) combinations. Calves (n = 230; 285 kg) were blocked by sex and weight into six replications and received FTH:MBM supplying 35% of the supplemental CP fed alone or with a high or low level of Trp supplement. Negative (urea only) and positive controls were included. Calves receiving FTH:MBM combinations gained faster (P less than .10) and were more efficient (P less than .10) than urea-supplemented calves. Performance was not altered by Trp addition. Calves (n = 120; 230 kg) were individually fed in two replications (43 or 48% CP MBM in Replications 1 and 2, respectively) of a growth trial to determine whether there was a complementary response between blood meal (BM) and MBM.(ABSTRACT TRUNCATED AT 250 WORDS)


Basic science and applied science instruction: are they compatible? Basic science and applied science instruction are compatible and essential for animal science professionals to succeed in their chosen career. Application of science is a continuum. Although production methods are constantly evolving, the science on which changes are made is fixed and fundamental. Only our understanding changes. We are educating students in preparation for a life-long learning process. Viability of animal science departments depends on attracting and challenging students with curricula that are demanding, create curiosity, and prepare students to understand the "whys and hows" of the phenomena of animal biology.


Modernizing the animal science curriculum: is change needed? To identify an animal science curriculum is difficult because it is a "moving target" due to changing needs and demands of our society and, more specifically, to changes in the backgrounds and interests of students. Therefore, animal science curriculums not only should change, but must change, if they are to succeed. With new technological innovations and discoveries that either modify, supplement, or change basic concepts and approaches, it is paramount that changes in courses as well as in the curriculum conform. Because of the applied nature of animal science and because of the many unknowns yet to be discovered, the curriculum should be under continual scrutiny. However, we must not fix something when it is not broken. For all practical purposes, a curriculum reflects a philosophy of what subjects should be included to complete a plan of study. After a philosophy has been established the base curriculum will seldom change significantly. When it does, it will be the result of a change in people's philosophies rather than a reflection of industry needs or student interests. Teachers should not forget how to teach most effectively the material and must never lose sight of their goal of molding students into knowledgeable, wise, and responsible citizens in our society.(ABSTRACT TRUNCATED AT 250 WORDS)


Purification and characterization of an imipenem hydrolysing metallo-beta-lactamase from Bacteroides fragilis. An imipenem resistant beta-lactamase producing strain of Bacteroides fragilis was isolated from a clinical specimen. The specific activity of the unpurified beta-lactamase was 5.5 U/mg protein. The beta-lactamase was purified 60-fold by Q Sepharose, Sephacryl S-300 and Mono Q column passages. The strain was able to inactivate imipenem and cefoxitin in broth cultures. The enzyme hydrolysed imipenem more rapidly than ampicillin, benzylpenicillin, cephalothin and cefoxitin. The activity of the enzyme was Zn2+ dependent and was completely inhibited by EDTA. The inhibition was reversed by ZnSO4. Preincubation with the common beta-lactamase inhibitors clavulanic acid, sulbactam and tazobactam did not reduce the enzyme activity. The molecular weight was determined by sodium dodecyl sulfate gradient gel electrophoresis to be 31,000 Daltons and the isoelectric point was 4.5.


Proposed mechanism for metronidazole resistance in Helicobacter pylori. Metronidazole MIC values were determined for ten isolates of Helicobacter pylori. Under microaerobic conditions four were inhibited by less than 0.25 mg/L, two strains required 2.0 mg/L and four strains had MIC greater than 32 mg/L. The strains were tested for their susceptibility to metronidazole after varying lengths of anaerobic exposure prior to or during microaerobic incubation. The susceptibility was determined by E-test and traditional agar dilution technique. The level of susceptibility of primarily susceptible strains was not significantly affected by a 2 to 24 h period of anaerobic incubation. However, the effect on resistant strains was dramatic. These strains were increasingly susceptible when a 2 to 12 h period of anaerobicity was provided anytime during the first 48 h and fully susceptible (MIC less than 0.1 mg/L) if 24 h of anaerobicity was provided. When tested again under microaerobic conditions the strains exhibited their original MIC values. The composition of the medium did not influence the results. We propose that "metronidazole resistance" in H. pylori is due to a decreased ability of these strains to achieve a sufficiently low redox potential under microaerobic conditions for the necessary reduction of metronidazole, and that these strains during short periods of anaerobicity manage to reduce and "store" sufficient amounts of metronidazole to appear fully susceptible after subsequent microaerobic incubation. microaerobic incubation.


Maintenance requirements of Escherichia coli ATCC 25922 in the presence of sub-inhibitory concentrations of various antibiotics. Escherichia coli ATCC 25922 was grown in minimal medium M63, with glucose 0.1 gL as limiting energy substrate, in the presence of sub-inhibitory concentrations of netilmicin, habekacin, tobramycin, dibekacin, amikacin, kanamycin, amoxycillin, ampicillin, cephalothin, cefoxitin and nalidixic acid. Maintenance requirements were determined with a simple relationship derived from batch growth curves. The apparent relationship between maintenance requirements and antibiotic concentration is an exponential increase, log m(c) = log mo + k.c, where m is maintenance, c antibiotics concentration, mo maintenance without antibiotics, and k a constant. Values for k were found to be in the range 0.5-2.0 mg-1.L.


The postantifungal effect of 5-fluorocytosine on Candida albicans. The in-vitro postantifungal effect (PAFE) of 5-fluorocytosine for Candida albicans for short periods of time was investigated. Yeast cells were exposed for 0.5, 1 or 2 h to a range of concentrations (0.1-3.2 mg/L) of 5-fluorocytosine. The PAFE was quantitated by determinations of the number of colony forming units at hourly intervals (0-10 h) after removal of the drug by dilution. The length of the PAFE was dependent upon the concentration of 5-fluorocytosine and the duration of exposure. An exposure time of 0.5 h resulted in PAFE's ranging from 0 to 4.2 h. Exposure times of 1 and 2 h resulted in longer PAFEs and in many instances suppression of cell growth was seen for the entire evaluation period (up to ten hours).


The IC50: an exactly defined measure of antibiotic sensitivity. The concentration of gentamicin that inhibits the growth of half of an inoculum of Pseudomonas aeruginosa (IC50) was estimated by doing viable bacterial counts with varying concentrations of gentamicin and fitting a probit inhibition curve to the results. This is a more precisely defined measure than the MIC and its standard error is readily calculable.


In-vitro activities of 14-, 15- and 16-membered macrolides against gram-positive cocci. The in-vitro activities of the 14-membered macrolides erythromycin, dirithromycin, roxithromycin, clarithromycin, the 15-membered compound azithromycin and the 16-membered macrolides (16 MM) josamycin, spiramycin and midecamycin acetate (MOM) have been compared against staphylococci, enterococci and streptococci. Results have been analysed separately according to the sensitivity status of the tested strains to erythromycin, namely sensitive (S), inducibly resistant (IR) or constitutively resistant (CR). 14- and 15-membered macrolides were active only against S strains; the order of potency in vitro was clarithromycin = erythromycin greater than azithromycin = roxithromycin greater than dirithromycin. The 16 MM were slightly less active against S strains than were the 14- and 15-membered compounds, and inhibited most IR strains; MOM and josamycin were about twice as potent as spiramycin. IR and S Staphylococcus aureus strains were equally sensitive to 16 MM, while IR strains of coagulase-negative staphylococci were less sensitive than were S strains. All CR strains of S. aureus were resistant to 16 MM, as were most of the other CR strains. However, 5/21 CR coagulase-negative staphylococci and 2/20 CR enterococci tested were sensitive to 16 MM. The seven CR strains showing anomalous sensitivity to the 16 MM (five Staphylococcus haemolyticus and two enterococci) were only 'moderately resistant' to erythromycin (MIC 8-64 mg/L), while all the other CR strains were 'highly resistant' (MIC greater than 128 mg/L). These results indicate that it may be difficult to predict the sensitivity of Gram-positive cocci to 16 MM, and therefore individual sensitivity testing to specific compounds is essential.


Surveillance of Streptococcus pneumoniae serotypes in Riyadh and their susceptibility to penicillin and other commonly prescribed antibiotics. A total of 358 recent distinct isolates of Streptococcus pneumoniae were recovered from clinical specimens of patients in various hospitals in Riyadh, Saudi Arabia. The commonest serotypes were Groups C, F, B and A. Using specific monosera for typing it was found that serotype 14 was the commonest followed by serotypes 3, 7, 1, 2, 19 and 8 respectively. The minimal inhibitory concentrations (MIC) of penicillin determined by an agar dilution method, showed that 81% were susceptible (MIC less than 0.1 mg/L), 18% were relatively resistant (MIC = 0.1-1 mg/L) and 1% showed increased resistance (MIC greater than or equal to 1.0 mg/L). The use of a 1 microgram oxacillin disc distinguished between susceptible and relatively penicillin resistant pneumococci more reliably than did the use of a penicillin disc (1 or 10 micrograms). Resistance of S. pneumoniae to tetracycline, co-trimoxazole, chloramphenicol, and erythromycin were 70%, 43%, 12% and 4% respectively. All isolates were susceptible to oral cephalosporins (cefadroxil, cephalexin, cefaclor, and cefuroxime axetil) with an MIC range of less than or equal to 0.03-2 mg/L. The selection of antimicrobial therapy and the efficiency of vaccines depend on the knowledge of the local isolates of S. pneumoniae. Clinical isolates should be routinely screened to detect susceptibility to penicillin. The relatively high incidence of resistance to multiple antibiotics indicates the need to perform antibiotic susceptibility testing in order to avoid possible therapeutic failure.


The spectrum of antibiotic resistance in human and veterinary isolates of Escherichia coli collected from 1984-86 in northern India. This study was undertaken to assess the spectrum of drug resistance prevalent in Escherichia coli isolates from human and animal populations in Northern India. Three hundred and two isolates of Escherichia coli isolated from various infections of humans (47 from diarrhoea; 101 from urinary tract infection) and veterinary animals (17 from poultry septicaemia; 75 from bovine diarrhoea; 14 from ovine diarrhoea and 48 from equine metritis) were studied for their susceptibility to ampicillin, cephaloridine, amoxycillin, cloxacillin, oxytetracycline, doxycycline, chloramphenicol, gentamicin, and trimethoprim-sulphamethoxazole. 63.2% of the isolates (37.7%, human; 25.5%, animal) were resistant to one or more drugs, of which about 41% isolates were multiresistant. Resistant isolates had a wide range of MIC values from 12 to 3200 mg/L, irrespective of origin. Most of the isolates (43.5%) were resistant to ampicillin (MIC greater than 16 mg/L) followed by oxytetracycline (MIC greater than 5 mg/L) (36.4%). Only 9.3% isolates were resistant to trimethoprim-sulphamethoxazole (MIC greater than 21 mg/L). The E. coli isolated from animals tended to be resistant to fewer antibiotics than those isolated from man. 99% of the isolates from human urinary tract infection were resistant compared to only 48.9% of the isolates from diarrhoea. Most of the resistant isolates from animals were recovered from diarrhoea, followed by septicaemia and metritis. This study shows that a high frequency of multiresistant strains are prevalent in both human and animal bacterial populations of Northern India. Since the exchange of these strains among both populations is possible, they pose a great risk in both the selection and the spread of resistance.


In-vitro activity of new carbapenem antibiotics: comparative studies with meropenem, L-627 and imipenem against pathogenic Nocardia spp. MICs of two new carbapenems, meropenem and L-627, and imipenem were determined against 98 strains of the Nocardia asteroides group (i.e. N. asteroides sensu stricto, Nocardia farcinica and Nocardia nova), 46 strains of Nocardia brasiliensis and 17 strains of Nocardia otitidiscaviarum. Meropenem and L-627 were less active against the N. asteroides group than imipenem. Among the three species of the N. asteroides group, N. nova was the most sensitive to all the carbapenems. Meropenem was more active than imipenem against both N. brasiliensis and N. otitidiscaviarum with MIC50 values of 28.3-53.3 mg/L. L-627 was less active than meropenem.


Effect of erythromycin on ciliary motility in rabbit airway epithelium in vitro. The effect of erythromycin on ciliary beat frequency (CBF) of rabbit tracheal epithelium was studied by a microphoto-oscillation technique in vitro. Addition of erythromycin dose-dependently increased CBF, the maximal increase from the baseline value and EC50 being 23.3 +/- 4.5% (P less than 0.001) and 6.8 +/- 0.9 mg/L, respectively. This effect was not influenced by autonomic receptor antagonists, blockers of arachidonic acid metabolism, Ca(2+)-free medium, or inhibition of protein kinase C and protein kinase A activities.


Pharmacokinetics and metabolism of FCE 22101 following its administration as the oral pro-drug FCE 22891. Ten healthy male volunteers who had previously received both intramuscular and intravenous doses of FCE 22101 received a single oral dose of FCE 22891, the acetoxymethyl ester and pro-drug of FCE 22101. After a lag time of 22 min, mean plasma levels of FCE 22101 rose with a T1/2 absorbance of 19 min to 2.5 mg/L at 30 min, 3.6 mg/L at 60 min and a Cmax of 4.6 mg/L at 80 min; levels then fell with a T1/2 beta of 29 min to be undetectable at 300 min. The mean area under the concentration-time curve (AUC) was 497 mg.min/L giving an absolute bioavailability for FCE 22101 of 32%. Neither FCE 22101 or its metabolites were present in any of the saliva samples collected at intervals up to 360 min after dosing. Mean urinary recoveries were FCE 22101 12% (+/- S.D. 4.6), P1 16% (+/- S.D. 9.1) and P2 3.3% (+/- S.D. 2.1). It was not possible to detect the pro-drug FCE 22891 in any of the blood or urine samples. Significant levels of the metabolite P1 were observed in blood with peak levels of 1.7 mg/L seen 130 min after dosing, 50 min later than the peak FCE 22101 levels, and giving a mean AUC of 297 mg.min/L.


Awareness of need and actual use of prophylaxis: lack of patient compliance in the prevention of bacterial endocarditis. Antibiotics are given before some medical and dental procedures to patients with congenital or acquired heart disease to prevent endocarditis. The majority of practitioners and patients are aware of the need for this prophylaxis, although in practice prophylaxis is administered infrequently. It is not known how often patients at risk for endocarditis undergo procedures which warrant the prophylactic administration of antibiotics, nor how often prophylaxis is actually administered to these patients. Two groups of adult patients and a group of children with a cardiac lesion predisposing to endocarditis were surveyed by either telephone interview or mailed questionnaire about awareness of the need for prophylaxis, procedures undergone within six months of the survey and the actual use of prophylaxis before these procedures. Of 455 patients surveyed, 371 (81.5%) responded, 258 (69.5%) of whom remembered receiving advice on prophylaxis. Recollection of advice ranged from 77% of those younger than sixty years to 48% of those aged sixty or older. The patients underwent 68 procedures for which prophylaxis was definitely indicated and 71 procedures with a possible indication for prophylaxis; 127 (91%) of these procedures were dental. Antibiotics were allegedly administered before the procedure to 31 patients (22%). There is marked discrepancy between recollection of the advice and actual use of prophylaxis. In view of this it is likely that patients often undergo procedures without antibiotic protection; however, only a few of these patients develop endocarditis.


A comparison of the costs of ceftazidime therapy and gentamicin combinations in three UK hospitals. This study compares the utilization costs of ceftazidime therapy with those of gentamicin in combination with other antibacterial drugs. The results show that the relatively high purchase cost of ceftazidime compared to combinations is more than counterbalanced by the additional materials used for drug administration and serum antibiotic assays, even when other drugs were combined with ceftazidime. The average drug and equipment costs were 230.13 pounds for ceftazidime regimens and 253.94 pounds for gentamicin regimens. It is also shown that ceftazidime therapy is associated with a reduction in personnel time compared to gentamicin regimens. The average times per patient for administration and assay were 1 h 43 min for ceftazidime and 4 h 57 min for gentamicin regimens. We conclude that ceftazidime regimens are cheaper than gentamicin regimens when all drug and equipment costs are quantified. Moreover, the use of ceftazidime will release staff time for other purposes.


Effect of subinhibitory antimicrobial concentrations (sub-MICs) on in-vitro bacterial adherence to uroepithelial cells. Subinhibitory antimicrobial concentrations have been reported to alter the adherence of bacteria to uroepithelial cells. Most investigators assessing the influence of subinhibitory antimicrobial concentrations on bacterial adherence in the urinary tract have employed in-vitro techniques using voided uroepithelial cells. These cells are incubated with bacteria previously exposed to antimicrobials and adherence is assessed by light microscopy. Most investigators have studied urinary Escherichia coli isolates. beta-Lactams, tetracyclines, aminoglycosides, nitrofurantoin, chloramphenicol, quinolones, trimethoprim and sulphonamides have been studied in concentrations ranging from 1/32-1/2x MIC. The following effects of subinhibitory antimicrobial concentrations on bacterial adherence have been reported: penicillins consistently reduce bacterial adherence at concentrations 1/4-1/2x MIC; nitrofurantoin and chloramphenicol demonstrate variable effects on bacterial adherence at 1/4x MIC; tetracyclines, but not doxycycline, decrease adherence at high concentrations (1/4-1/2x MIC) and increase it at low concentrations (1/8-1/32x MIC); both trimethoprim and sulphonamides consistently decrease bacterial adherence at concentrations ranging from 1/32-1/2x MIC and 1/4-1/2x MIC, respectively, but it is unclear whether the combination of trimethoprim and a sulphonamide decreases bacterial adherence to a greater extent than either agent alone; aminoglycosides decrease adherence at 1/2x MIC; and quinolones decrease adherence at 1/4x MIC, with variable effects at 1/8x MIC and 1/16x MIC. Subinhibitory antimicrobial concentrations may exert their antiadhesive effects through suppression of formation and/or expression on the surface adhesin, the formation of functionally aberrant adhesins, or a direct effect on the bacterial surface. Presently, the clinical significance of the alterations in bacterial adherence to uroepithelial cells is not fully understood.


Characterization of chromosomally encoded penicillinases in clinical isolates of Klebsiella pneumoniae. Four Klebsiella pneumoniae strains, isolated in two geographically distant French hospitals, were found to produce constitutive beta-lactamases with an unusual isoelectric point for this species (8.1). The four enzymes were chromosomally encoded and related to the Ambler's class A plasmid-mediated SHV-type enzymes. The four enzymes were predominantly penicillinases, with good activity against amino- and ureidopenicillins. They poorly hydrolysed cephalothin, cephaloridine and cefoperazone and did not hydrolyse third-generation cephalosporins and aztreonam. The four enzymes were susceptible to the inhibitory effect of clavulanic acid. Finally, the strains were all found to produce an acetyl-esterase. The acetyl-esterases catalysized hydrolysis of the acetoxy group of cephalothin and cefotaxime although this did not affect their antibacterial activities. These esterases were not susceptible to the inhibitory effect of clavulanic acid and EDTA.


In-vitro activity of tosufloxacin, a new quinolone antibacterial agent. The in-vitro activity of tosufloxacin (A-61827) was compared with that of temafloxacin, ciprofloxacin and selected members of other groups of antimicrobial agents, against 684 recent distinct clinical isolates and strains with known mechanisms of resistance. Against members of the Enterobacteriaceae, ciprofloxacin was slightly more active than tosufloxacin, which was more active than temafloxacin. The MIC90 of tosufloxacin for all species of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. was less than or equal to 1 mg/L. Tosufloxacin was slightly more active than temafloxacin, and four to eight fold more active than ciprofloxacin, against the Gram-positive species tested. The MIC90 of tosufloxacin for Staphylococcus aureus was 0.12 mg/L, and for Streptococcus pneumoniae was 0.5 mg/L. All strains of Neisseria spp., Haemophilus influenzae and Moraxella catarrhalis were inhibited by tosufloxacin at a concentration of less than or equal to 0.12 mg/L. Tosufloxacin was the most active quinolone against the anaerobic organisms tested. Cross resistance between quinolones was seen, but not between quinolones and other groups of antimicrobials. The protein binding of tosufloxacin across a range of concentrations averaged 60%. Human serum at a concentration of 70% decreased the bactericidal activity of tosufloxacin by about four-fold.


Comparison of the in-vitro activities of the topical antimicrobials azelaic acid, nitrofurazone, silver sulphadiazine and mupirocin against methicillin-resistant Staphylococcus aureus. The in-vitro activities of the topical agents azelaic acid, nitrofurazone, silver sulphadiazine and mupirocin have been determined against 80 strains of MRSA collected from worldwide sources. MICs were determined by agar dilution (with an inoculum of approximately 5.0 x 10(5) cfu) in Iso-Sensitest agar, and MBCs were measured by replica-plating from MIC plates using velvet pads. The agents tested were uniformly active against MRSA, mupirocin being the most active (MIC50 0.15 mg/L) followed by nitrofurazone (MIC50 19 mg/L), silver sulphadiazine (MIC50 85 mg/L) and azelaic acid (MIC50 850 mg/L). Concentrations of azelaic acid, nitrofurazone and silver sulphadiazine close to the MIC were bactericidal, but mupirocin was only bactericidal at concentrations substantially greater than the MIC. In time-kill experiments, azelaic acid and nitrofurazone were gradually bactericidal, silver sulphadiazine was rapidly bactericidal and mupirocin was not bactericidal. Silver sulphadiazine killed sulphonamide-sensitive and sulphonamide-resistant strains equally rapidly. No resistant mutants were found to azelaic acid, nitrofurazone or silver sulphadiazine in an inoculum of 10(9) cfu, but two strains yielded (frequency: 1.0 x 10(-9)) mutants resistant to mupirocin. Our in-vitro results suggest azelaic acid, nitrofurazone and silver sulphadiazine could be of use for clearing staphylococcal carriage.


Effect of impaired renal function on the pharmacokinetics of coadministered cefoperazone and sulbactam. The pharmacokinetics of cefoperazone 2 g combined with sulbactam 1 g after a single dose administered intravenously were evaluated in 24 subjects with normal and impaired renal function. Subjects were categorized into four groups based on endogenous creatinine clearance Clcr. Patients in groups 1, 2 and 3 had ClcrS of greater than 60, 31 to 60, and 10 to 30 mL/min/1.73 m2, respectively. Patients in group 4 required maintenance haemodialysis and were assumed to have Clcr less than 10 mL/min/1.73 m2. Pharmacokinetic parameters were determined by noncompartmental methods. No significant differences (P greater than 0.05) in mean peak serum cefoperazone-sulbactam concentrations for group 1 (208.4/29.0 mg/L), group 2 (199.0/34.1 mg/L), group 3 (163.2/35.0 mg/L), and group 4 (234.0/66.0 mg/L) were noted. Correlations between both total serum (r = 0.58) and renal (r = 0.35) clearance and creatinine clearances were negative for cefoperazone, although both were shown to decline with diminished renal function. Correlations between serum (r = 0.85) and renal (r = 0.72) clearances and creatinine clearance for sulbactam were, on the other hand, both positive and declined in a linear fashion. No significant differences in steady state volumes of distribution were noted for either cefoperazone (P = 0.53) or sulbactam (P = 0.85) amongst the four groups. After 24 h, urinary recovery was also comparable for both cefoperazone (P = 0.64) and sulbactam (P = 0.85) amongst the four groups. The concentrations of cefoperazone and sulbactam remained at or above the MICs (16/8 mg/L) for common bacterial pathogens for 2.5, 3, 7 and 14 h in groups 1, 2, 3 and 4, respectively.


A study of the penetration of meropenem into bile using endoscopic retrograde cholangiography. One gram of meropenem was administered as prophylaxis to patients undergoing endoscopic retrograde cholangiography (ERC) in a study of the bile pharmacokinetics of this agent. Twenty-four patients were evaluated and a single bile sample was collected from each one during ERC at different time intervals following intravenous infusion. Bile concentrations after the dose ranged from 0.7 to 25.7 mg/L (mean 11.1) and exceeded the MIC90s for the pathogens most commonly associated with biliary tract infections for up to 203 mins. The bile concentrations of 13 patients with biliary tree obstruction were compared with those of 11 patients without obstruction. Bile concentrations in excess of the MIC90s for the predominant pathogens were achieved in both groups; a positive correlation between meropenem bile concentration and the time of dose administration was demonstrable only for the obstructed group. ERC may be a useful technique for biliary pharmacokinetic studies.


Penetration of rifampicin into the cerebrospinal fluid of adults with uninflamed meninges. The penetration of rifampicin into CSF was studied in seven patients who had undergone external ventriculostomy for occlusive hydrocephalus without major disturbance of the blood-CSF barrier. After the first dose of rifampicin 600 mg i.v. over 3 h, blood and CSF concentrations were determined serially by HPLC. Peak CSF concentrations obtained 0-8 h (median = 1 h) after the end of the infusion ranged from 0.57 to 1.24 mg/L (median = 0.73 mg/L). Elimination from CSF was slower than from serum (T1/2 beta CSF: 9.1-21.0 h (median = 14.5 h, n = 5); T1/2 beta serum: 2.2-5.8 h (median = 3.6 h, n = 7)). Based on the ratios of the areas under the concentration-time curves in CSF and serum, the overall penetration of rifampicin into CSF was 0.13-0.42 (median = 0.22). These results demonstrate effective CSF penetration and favourable pharmacokinetics of rifampicin in the absence of meningeal inflammation. They support the use of rifampicin as part of a combination therapy not only for tuberculosis of the central nervous system (CNS), but also for staphylococcal and listerial infections of the CNS in which there may be little meningeal inflammation.


Respiratory and circulatory activities in carotid body-resected humans. The respiratory and circulatory activities of patients who underwent carotid body resection (CBR) more than two decades ago were reviewed. No significant ventilatory response to continuous hypoxia was observed. However, in response to stimulation of peripheral chemoreceptors, transient hyperventilation occurred before hypoxemic blood arrived at the central nervous system (single-breath test), which indicated the presence of weak peripheral chemosensitivity. Because of this slight residual peripheral chemosensitivity, which was found shortly after the operation and apparently remained more or less unchanged for greater than 20 years, peripheral chemoreceptor activity, which has been reported in other animal species, does not seem to have returned. Delayed hypoxic hyperventilation reported in dogs and cats with CBR was not observed. Hypoxia significantly depressed the ventilatory response to CO2, but the delayed ventilatory depression with time that has been demonstrated in normal subjects did not occur. In our circulatory studies, hypoxia augmented the heart rate and slightly depressed the stroke volume and total peripheral resistance in the systemic circulation but induced no appreciable changes in arterial blood pressure or cardiac output. We used these results to partition the relative contributions to the overall circulatory response of carotid body stimulation, pulmonary inflation, and other modifying influences. From these calculations, it was inferred that the carotid body reflex plays a dominant role in vascular activities whereas the pulmonary inflation reflex dominates in cardiac activities in humans.


Augmented hypoxic ventilatory response in men at altitude. To test the hypothesis that the hypoxic ventilatory response (HVR) of an individual is a constant unaffected by acclimatization, isocapnic 5-min step HVR, as delta VI/delta SaO2 (l.min-1.%-1, where VI is inspired ventilation and SaO2 is arterial O2 saturation), was tested in six normal males at sea level (SL), after 1-5 days at 3,810-m altitude (AL1-3), and three times over 1 wk after altitude exposure (PAL1-3). Equal medullary central ventilatory drive was sought at both altitudes by testing HVR after greater than 15 min of hyperoxia to eliminate possible ambient hypoxic ventilatory depression (HVD), choosing for isocapnia a P'CO2 (end tidal) elevated sufficiently to drive hyperoxic VI to 140 ml.kg-1.min-1. Mean P'CO2 was 45.4 +/- 1.7 Torr at SL and 33.3 +/- 1.8 Torr on AL3, compared with the respective resting control end-tidal PCO2 of 42.3 +/- 2.0 and 30.8 +/- 2.6 Torr. SL HVR of 0.91 +/- 0.38 was unchanged on AL1 (30 +/- 18 h) at 1.04 +/- 0.37 but rose (P less than 0.05) to 1.27 +/- 0.57 on AL2 (3.2 +/- 0.8 days) and 1.46 +/- 0.59 on AL3 (4.8 +/- 0.4 days) and remained high on PAL1 at 1.44 +/- 0.54 and PAL2 at 1.37 +/- 0.78 but not on PAL3 (days 4-7). HVR was independent of test SaO2 (range 60-90%). Hyperoxic HCVR (CO2 response) was increased on AL3 and PAL1. Arterial pH at congruent to 65% SaO2 was 7.378 +/- 0.019 at SL, 7.44 +/- 0.018 on AL2, and 7.412 +/- 0.023 on AL3.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of tidal volume and PEEP in ethchlorvynol-induced asymmetric lung injury. We examined the effects of positive end-expiratory pressure (PEEP) and tidal volume on the distribution of ventilation and perfusion in a canine model of asymmetric lung injury. Unilateral right lung edema was established in 10 animals by use of a selective infusion of ethchlorvynol. Five animals were tested in the supine position (horizontal asymmetry) and five in the right decubitus position (vertical asymmetry). Raising PEEP from 5 to 12 cmH2O improved oxygenation despite a redistribution of blood flow toward the damage lung and a consistent decrease in total respiratory system compliance. This improvement paralleled a redistribution of tidal ventilation to the injured lung. This was effected primarily by a fall in the compliance of the noninjured lung due to hyperinflation. The effects of higher tidal volume were additive to those of PEEP. We propose that the major effect of PEEP in inhomogeneous lung injury is to restore tidal ventilation to a population of alveoli recruitable only at high airway pressures.


Circulating neuropeptide Y does not produce pulmonary hypertension during massive sympathetic activation. We tested the possibility that neuropeptide Y (NPY) may contribute to the pulmonary hypertension that occurs after massive sympathetic activation produced by intracisternal veratrine administration in the chloralose-anesthetized dog. In six dogs, veratrine caused arterial NPY-like immunoreactivity (NPY-LI) to rise from 873 +/- 150 (SE) pg/ml to peak values of 3,780 +/- 666 pg/ml by 60-120 min. (In 3 animals, adrenalectomy significantly reduced the increases in NPY-LI.) In five additional dogs, we infused porcine NPY for 30 min in doses that increased arterial NPY-LI to 8,354 +/- 1,514 pg/ml and observed only minor changes in pulmonary hemodynamics. In three isolated perfused canine left lower lung lobe (LLL) preparations, increasing doses of NPY were administered, producing levels of plasma NPY-LI, at the highest dose, that exceeded those observed after veratrine administration by three orders of magnitude. No changes in LLL arterial or double-occlusion capillary pressures were observed at any dose. Similarly, no changes in LLL hemodynamics were observed in three additional lobes when NPY was administered while norepinephrine was being infused. We conclude that it is unlikely that NPY plays a role as a circulating vasoactive agent in producing the pulmonary hypertension and edema that occur in this model.


High lung volume increases stress failure in pulmonary capillaries. We previously showed that when pulmonary capillaries in anesthetized rabbits are exposed to a transmural pressure (Ptm) of approximately 40 mmHg, stress failure of the walls occurs with disruption of the capillary endothelium, alveolar epithelium, or sometimes all layers. The present study was designed to test whether stress failure occurred more frequently at high than at low lung volumes for the same Ptm. Lungs of anesthetized rabbits were inflated to a transpulmonary pressure of 20 cmH2O, perfused with autologous blood at 32.5 or 2.5 cmH2O Ptm, and fixed by intravascular perfusion. Samples were examined by both transmission and scanning electron microscopy. The results were compared with those of a previous study in which the lung was inflated to a transpulmonary pressure of 5 cmH2O. There was a large increase in the frequency of stress failure of the capillary walls at the higher lung volume. For example, at 32.5 cmH2O Ptm, the number of endothelial breaks per millimeter cell lining was 7.1 +/- 2.2 at the high lung volume compared with 0.7 +/- 0.4 at the low lung volume. The corresponding values for epithelium were 8.5 +/- 1.6 and 0.9 +/- 0.6. Both differences were significant (P less than 0.05). At 52.5 cmH2O Ptm, the results for endothelium were 20.7 +/- 7.6 (high volume) and 7.1 +/- 2.1 (low volume), and the corresponding results for epithelium were 32.8 +/- 11.9 and 11.4 +/- 3.7. At 32.5 cmH2O Ptm, the thickness of the blood-gas barrier was greater at the higher lung volume, consistent with the development of more interstitial edema. Ballooning of the epithelium caused by accumulation of edema fluid between the epithelial cell and its basement membrane was seen at 32.5 and 52.5 cmH2O Ptm. At high lung volume, the breaks tended to be narrower and fewer were oriented perpendicular to the axis of the pulmonary capillaries than at low lung volumes. Transmission and scanning electron microscopy measurements agreed well. Our findings provide a physiological mechanism for other studies showing increased capillary permeability at high states of lung inflation.


Substrate and endocrine responses during exercise at selected stages of pregnancy. To determine whether the concomitant effects of pregnancy and exercise yield substrate and endocrine patterns different from those expected during exercise alone, we compared the responses of glucose, lactate, free fatty acids, insulin, epinephrine (EP), norepinephrine (NE), human chorionic gonadotropin (HCG), human placental lactogen (HPL), estriol, and progesterone (P) in nonpregnant women (NP; n = 7) and pregnant women in the second (TR2; n = 6) and third trimester (TR3; n = 8) of pregnancy, before, during, and after 30 min of bicycle ergometer exercise at heart rates of 130-140 beats/min. In general, all substrates and hormone concentrations increased with exercise (P less than 0.05), except insulin, which decreased (P less than 0.05), and HCG, which did not change (P = 0.08). Differences in selected hormone concentrations (P, estriol, HCG, and HPL) among groups were already present at rest because of the different stages of pregnancy. Differences among groups at rest were also found in insulin and NE (P less than 0.05). Significantly different responses to exercise (i.e., group x time interactions) were as follows. NP vs. TR2:P, estriol, HCG, HPL, EP, and NE (P less than 0.05); NP vs. TR3: glucose, EP, and NE (P less than 0.05); TR2 vs. TR3: lactate, EP, and NE (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


A time-course study of the effects of pentobarbital, fentanyl, and morphine chloralose on myocardial mechanics. Cardiovascular physiological studies in anesthetized animals may be confounded by the hemodynamic actions of the anesthetic agents themselves. To identify an anesthetic regimen that does not significantly influence cardiovascular physiology, the hemodynamic responses of 28 dogs were studied. Animals were equally divided among groups with 1) no anesthesia (i.e., trained conscious preparation), 2) pentobarbital sodium, 3) fentanyl citrate, and 4) a combination of morphine sulfate and alpha-chloralose. Anesthesia was maintained for 3 h. Data were acquired with the use of ultrasound imaging of the heart in conjunction with invasive pressure measurements. Left ventricular ejection phase indexes and end-systolic force-velocity relations were used to evaluate the effects of each anesthetic agent on overall systolic performance and myocardial contractility. Compared with the conscious animals, pentobarbital profoundly depressed systolic performance (P less than 0.05 vs. control) because of a reduction in myocardial contractility (P less than 0.01) and an increase in left ventricular afterload (end-systolic wall stress, P less than 0.05). Fentanyl increased myocardial contractility (P less than 0.05) but also tended to increase afterload with the net result that overall systolic performance remained unchanged. Morphine-chloralose did not affect overall ventricular systolic performance or its individual determinants. Pentobarbital and fentanyl also caused progressive time-dependent deteriorations in all parameters of systolic function during prolonged anesthesia. In contrast, cardiac function was stable for greater than or equal to 3 h after induction of morphine-chloralose anesthesia. The hemodynamic profile of dogs anesthetized with morphine-chloralose most closely resembled that of the conscious animals. Morphine-chloralose is recommended when prolonged anesthesia is required for studies of cardiovascular physiology.


Capillary and fiber geometry in rat diaphragm perfusion fixed in situ at different sarcomere lengths. To determine the potential range of diaphragm sarcomere lengths in situ and the effect of changes in sarcomere length on capillary and fiber geometry, rat diaphragms were perfusion fixed in situ with glutaraldehyde at different airway pressures and during electrical stimulation. The lengths of thick (1.517 +/- 0.007 microns) and thin (1.194 +/- 0.048 microns) filaments were not different from those established for rat limb muscle. Morphometric techniques were used to determine fiber cross-sectional area, sarcomere length, capillary orientation, and capillary length and surface area per fiber volume. All measurements were referenced to sarcomere length, which averaged 2.88 +/- 0.08 microns at -20 to -25 cmH2O airway pressure (residual volume) and 2.32 +/- 0.05 microns at +20 to +26 cmH2O airway pressure (total lung capacity). The contribution of capillary tortuosity and branching to total capillary length was dependent on sarcomere length and varied from 5 to 22%, consistent with that shown previously for mammalian limb muscles over this range of sarcomere lengths. Capillary length per fiber volume [Jv(c,f)] was significantly greater at residual volume (3,761 +/- 193 mm-2) than at total lung capacity (3,142 +/- 118 mm-2) and correlated with sarcomere length [l; r = 0.628, Jv(c,f) = 876l + 1,156, P less than 0.01; n = 18]. We conclude that the diaphragm is unusual in that the apparent in situ minimal sarcomere length is greater than 2.0 microns.(ABSTRACT TRUNCATED AT 250 WORDS)


Influence of human muscle length on energy transduction studied by 31P-NMR. Muscle contractions at lengths below the optimum for force development were previously found to cause less fatigue than contractions at the optimum length (Lo). Decreased fatigability was suggested to arise from fewer cross-bridge interactions in shortened sarcomeres. In the present study, this suggestion was tested by monitoring energy use of human ankle dorsiflexor muscles during and after contractions at Lo and shortened lengths (Ls) with phosphorus nuclear magnetic resonance spectroscopy. The nuclear magnetic resonance spectra indicated similar rates of ATP use during contractions at Lo and Ls. Phosphocreatine, at an initial concentration of 37 mM, was reduced to an equivalent extent by 2 min of ischemic exercise at Lo (to 2.3 mM) and Ls (to 4.7 mM). Changes in pH (indicating glycolytic ATP production) were also equivalent at Lo and Ls. Exercise caused pH to fall from an initial level of 7.07 to 6.5 at Lo and to 6.53 at Ls. In relation to previous experiments performed under similar conditions on human ankle dorsiflexor muscles, the present experiments suggest that in shortened muscle the decreased force found in this and previous studies and the decreased fatigability that was previously found may not be simply due to fewer cross-bridge interactions in shortened sarcomeres. Examination of the relationships between developed force and levels of metabolites suggests that changes of force during fatigue and recovery correlate better with intracellular [Pi] and H2PO4- than with [H+].


Effects of cold on vascular permeability and edema formation in the isolated cat limb. We investigated the effects of cold temperatures on microvascular protein permeability in the isolated constant-flow perfused cat hindlimb. The perfusates were 20% cat plasma-80% albumin-electrolyte solution (low-viscosity perfusate, approximately 1 cP) or whole blood (high-viscosity perfusate, approximately 4 cP). The time at low temperature (less than 10 degrees C) was less than 3 h (short term) or greater than 5 h (long term). Decreases in the solvent drag reflection coefficient (sigma f) indicated increases in permeability. The sigma f's were determined with the integral-mass balance method from measurement of changes in protein concentration and hematocrit induced by fluid filtration into the tissues. Short-term cold exposure did not increase permeability with either a low- or a high-viscosity perfusate, whereas long-term exposure with limb temperatures of approximately 5 degrees C significantly increased permeability when the perfusate was whole blood. In addition, we verified our previous prediction that flow had to be reduced to 6-8 ml.min-1.100 g-1 to avoid the hydrostatic edema caused by short-term perfusion with whole blood at approximately 5 degrees C. Also, we found that at approximately 3 degrees C histamine's permeability-increasing effect was totally abolished, whereas at approximately 20 degrees C this effect was partially inhibited. Hence, constant-flow perfusion at low temperature with whole blood can cause edema by a pressure-dependent mechanism, whereas long-term perfusion with this perfusate at low temperatures can cause a permeability increase that further compounds edema formation. Histamine is not responsible for this permeability increase.


Tumor necrosis factor-alpha does not cause lung edema in rabbits. Although tumor necrosis factor-alpha (TNF) is a key mediator in the pathophysiology of sepsis and septic shock, its role in lung microvascular injury is controversial. In isolated blood-perfused rabbit lungs, we studied the microvascular effects of human recombinant TNF by measuring the capillary filtration coefficient (Kf,c) as an index of microvascular leakiness and the arterial and venous resistances and occlusion pressures to define the microvascular pressure profile. At the end of the experiments, the lung wet-to-dry weight ratio (W/D) was determined as an index of edema. TNF increased the pulmonary venous resistance slightly but did not affect Kf,c or W/D. Furthermore, TNF at different doses failed to increase W/D less than or equal to 8 h after in vivo administration. Our data suggest that 1) the pulmonary microvascular response to TNF differs from the systemic response, which is characterized by arteriolar vasodilation, and 2) TNF is insufficient to cause lung edema, both in vivo and in vitro. Thus the development of lung microvascular injury may require the combined action of TNF and other mediators.


Effect of hypothyroidism on myosin heavy chain expression in rat pharyngeal dilator muscles. Although the association between hypothyroidism and obstructive sleep apnea is well established, the effect of thyroid hormone deficiency on contractile proteins in pharyngeal dilator muscles responsible for maintaining upper airway patency is unknown. In the present study, the effects of hypothyroidism on myosin heavy chain (MHC) expression were examined in the sternohyoid, geniohyoid, and genioglossus muscles of adult rats (n = 20). The relative proportions of MHC isoforms present were determined using MHC-specific monoclonal antibodies and oligonucleotide probes. All control muscles showed a paucity of type I MHC fibers, with greater than 90% of fibers containing fast-twitch type II MHCs. In the genioglossus muscle, a population of non-IIa non-IIb fast-twitch type II fibers (putatively identified as type IIx MHC fibers) were detected. Hypothyroidism induced significant changes in MHC expression in all muscles studied. In the sternohyoid, type I fibers increased from 6.2 to 16.9%, whereas type IIa fibers increased from 25.9 to 30.7%. Type I fibers in the geniohyoid increased from 1.2 to 12.8%, whereas type IIa fibers increased from 34.1 to 42.7%. The genioglossus showed the smallest relative increase in type I expression but the greatest induction of type IIa MHC. None of the muscles examined demonstrated reinduction of embryonic or neonatal MHC in response to thyroid hormone deficiency. In summary, hypothyroidism alters the MHC profile of pharyngeal dilators in a muscle-specific manner. These changes may play a role in the pathogenesis of obstructive apnea in hypothyroid patients.