Automated finite element meshing of the lumbar spine: Verification and validation with 18 specimen-specific models.

The purpose of this study was to seek broad verification and validation of human lumbar spine finite element models created using a previously published automated algorithm. The automated algorithm takes segmented CT scans of lumbar vertebrae, automatically identifies important landmarks and contact surfaces, and creates a finite element model. Mesh convergence was evaluated by examining changes in key output variables in response to mesh density. Semi-direct validation was performed by comparing experimental results for a single specimen to the automated finite element model results for that specimen with calibrated material properties from a prior study. Indirect validation was based on a comparison of results from automated finite element models of 18 individual specimens, all using one set of generalized material properties, to a range of data from the literature. A total of 216 simulations were run and compared to 186 experimental data ranges in all six primary bending modes up to 7.8Nm with follower loads up to 1000N. Mesh convergence results showed less than a 5% difference in key variables when the original mesh density was doubled. The semi-direct validation results showed that the automated method produced results comparable to manual finite element modeling methods. The indirect validation results showed a wide range of outcomes due to variations in the geometry alone. The studies showed that the automated models can be used to reliably evaluate lumbar spine biomechanics, specifically within our intended context of use: in pure bending modes, under relatively low non-injurious simulated in vivo loads, to predict torque rotation response, disc pressures, and facet forces.

Neurodevelopmental Outcome of Childhood Cancer Survivors Treated at the Eric Williams Medical Sciences Complex.

OBJECTIVE: To investigate the neurodevelopmental outcome of childhood cancer survivors treated at the Eric Williams Medical Sciences Complex (EWMSC). METHODS: Study participants were children treated at EWMSC from January 2003 to March 31, 2012 for various childhood cancers. All had completed treatment and were in remission. The McCarthy Scales of Children's Abilities (MSCA) was administered. The study was conducted from December 2011 to March 31, 2012. RESULTS: Twenty-six children were evaluated, a response rate of 74%. There were 12 males and 14 females. Ages ranged from 3.25 to 9.00 years. Four (15.4%) children scored a general cognitive index (GCI) < 68. One child (3.8%) scored a GCI > 132. The children's mean estimated mental age was found to be significantly lower than their mean actual age (p = 0.0086). Children treated for solid tumours had the least difference between their actual ages and estimated mental ages (p = 0.0301). The mean GCI for the genders was 97.4 for females and 81.0 for males; this difference was statistically significant (p = 0.0302). Age at diagnosis, type and length of treatment were not found to significantly affect development. CONCLUSION: The paediatric cancer survivors in this survey were found to have delays in their development. This group of children should have their development closely monitored. This would ensure that any delays in development can be discovered early and appropriate interventions instituted, so that childhood cancer survivors are adequately prepared for adult life beyond cancer.

Reverse engineering an amyloid aggregation pathway with dimensional analysis and scaling.

Human islet amyloid polypeptide (hIAPP) is a cytotoxic protein that aggregates into oligomers and fibrils that kill pancreatic ß-cells. Here we analyze hIAPP aggregation in vitro, measured via thioflavin-T fluorescence. We use mass-action kinetics and scaling analysis to reconstruct the aggregation pathway, and find that the initiation step requires four hIAPP monomers. After this step, monomers join the nucleus in pairs, until the first stable nucleus (of size approximately 20 monomers) is formed. This nucleus then elongates by successive addition of single monomers. We find that the best-fit of our data is achieved when we include a secondary fibril-dependent nucleation pathway in the reaction scheme. We predict how interventions that change rates of fibril elongation or nucleation rates affect the accumulation of potentially cytotoxic oligomer species. Our results demonstrate the power of scaling analysis in reverse engineering biochemical aggregation pathways.

Screening thoroughbreds for antibodies to the Equine infectious anemia virus.

One hundred and seventy two Thoroughbreds were screened for the presence of anitbodies to the capsid protein, p26 of the equine infectious anemia (EIA)virus using agarose gel immunodiffusion (AGOD) Coggins test. Horses ranged in age from 1 month to 21 years old and were either imported or locally bred. The majority were involved in racing and breeding and were housed either at the Santa Rosa Racing Complex at Arima or at privately owned farms. Complete blood counts (CBCs) were performed on all horses. Low haemoglobin concentrations were found in 18(10.5%), high white blood cell counts in 17 (9.9%) with neutrophilia in 13 (7.6%). Low red blood cell counts were seen in 11 of 154 horses (7.1%). At least 12 horses had evidence of clinical babesiosis, but only 7 were confirmed infected by examination of Giemsa stained blood smears. Racehorses from trinidad and Tobago occasionally move inter-island for racing and increasingly come in contact with foreign horses with the increasing importation of horses from countries known to harbour the virus. All 172 horses tested negative for antibodies to EIA virus. This implies that the strict adherence to import and quarantine regulations may have contributed to keeping the country free from EIA virus. This ongoing study is the first to provide sero-prevalence data and document the prevalence of EIA in the equine population in Trinidad and Tobago.

Screening thoroughbreds for antibodies to the Equine infectious anemia virus.

One hundred and seventy two Thoroughbreds were screened for the presence of anitbodies to the capsid protein, p26 of the equine infectious anemia (EIA)virus using agarose gel immunodiffusion (AGOD) Coggins test. Horses ranged in age from 1 month to 21 years old and were either imported or locally bred. The majority were involved in racing and breeding and were housed either at the Santa Rosa Racing Complex at Arima or at privately owned farms. Complete blood counts (CBCs) were performed on all horses. Low haemoglobin concentrations were found in 18(10.5%), high white blood cell counts in 17 (9.9%) with neutrophilia in 13 (7.6%). Low red blood cell counts were seen in 11 of 154 horses (7.1%). At least 12 horses had evidence of clinical babesiosis, but only 7 were confirmed infected by examination of Giemsa stained blood smears. Racehorses from trinidad and Tobago occasionally move inter-island for racing and increasingly come in contact with foreign horses with the increasing importation of horses from countries known to harbour the virus. All 172 horses tested negative for antibodies to EIA virus. This implies that the strict adherence to import and quarantine regulations may have contributed to keeping the country free from EIA virus. This ongoing study is the first to provide sero-prevalence data and document the prevalence of EIA in the equine population in Trinidad and Tobago.

Effect of chromium propionate and metabolizable energy on growth, carcass traits, and pork quality of growing-finishing pigs.

An experiment was conducted to evaluate the dietary effects of Cr propionate (CrProp) and metabolizable energy (ME) on growth, carcass traits, and pork quality of growing-finishing pigs. One hundred forty-four Cambrough-22 barrows were allotted to four dietary treatments in a randomized complete block design (six replicates of six pigs per replicate; average initial and final body weight were 27 and 113 kg, respectively). The dietary treatments were: 1) corn-soybean meal basal (B; low ME), 2) B + 200 ppb of Cr (as CrProp), 3) B + 200 kcal ME/kg (4.5% added fat; high ME), or 4) B + 200 kcal ME/kg + 200 ppb of Cr. At trial termination, three pigs per replicate were killed to determine dietary effects on carcass traits and pork quality. Overall average daily gain, average daily feed intake, and gain:feed ratio were not affected (P > 0.10) by diet. During the early growing period, average daily gain was increased in pigs fed the CrProp-low-ME diets, but decreased in pigs fed the CrProp-high ME diets (Cr x ME, P < 0.04). Feed intake was increased (P < 0.05) in pigs fed the high-ME diets during the early growing period. Forty-five min and 24 h pH were not affected (P > 0.10) by diet. The CIE L* tended (P = 0.07) to be increased and shear force tended (P = 0.06) to be decreased in pigs fed high-ME diets. Subjective marbling was increased (P < 0.03) and longissimus muscle percentage moisture and thaw loss were decreased (P < 0.04) in pigs fed CrProp. Chromium propionate had no consistent effect on growth and carcass traits in this experiment; however, CrProp did affect some aspects of pork quality.

Chronic toxicity/oncogenicity study of styrene in CD-1 mice by inhalation exposure for 104 weeks.

Groups of 70 male and 70 female Charles River CD-1 mice were exposed whole body to styrene vapor at 0, 20, 40, 80 or 160 ppm 6 h per day 5 days per week for 98 weeks (females) or 104 weeks (males). The mice were observed daily; body weights, food and water consumption were measured periodically, a battery of hematological and clinical pathology examinations were conducted at weeks 13, 26, 52, 78 and 98 (females)/104 (males). Ten mice of each gender per group were pre-selected for necropsy after 52 and 78 weeks of exposure and the survivors of the remaining 50 of each gender per group were necropsied after 98 or 104 weeks. An extensive set of organs from the control and high-exposure mice were examined histopathologically, whereas target organs, gross lesions and all masses were examined in all other groups. Styrene had no effect on survival in males. Two high-dose females died (acute liver toxicity) during the first 2 weeks; the remaining exposed females had a slightly higher survival than control mice. Levels of styrene and styrene oxide (SO) in the blood at the end of a 6 h exposure during week 74 were proportional to exposure concentration, except that at 20 ppm the SO level was below the limit of detection. There were no changes of toxicological significance in hematology, clinical chemistry, urinalysis or organ weights. Mice exposed to 80 or 160 ppm gained slightly less weight than the controls. Styrene-related non-neoplastic histopathological changes were found only in the nasal passages and lungs. In the nasal passages of males and females at all exposure concentrations, the changes included respiratory metaplasia of the olfactory epithelium with changes in the underlying Bowman's gland; the severity increased with styrene concentration and duration of exposure. Loss of olfactory nerve fibers was seen in mice exposed to 40, 80 or 160 ppm. In the lungs, there was decreased eosinophilia of Clara cells in the terminal bronchioles and bronchiolar epithelial hyperplasia extending into alveolar ducts. Increased tumor incidence occurred only in the lung. The incidence of bronchioloalveolar adenomas was significantly increased in males exposed to 40, 80 or 160 ppm and in females exposed to 20, 40 and 160 ppm. The increase was seen only after 24 months. In females exposed to 160 ppm, the incidence of bronchiolo-alveolar carcinomas after 24 months was significantly greater than in the controls. No difference in lung tumors between control and styrene-exposed mice was seen in the intensity or degree of immunostaining, the location of tumors relative to bronchioles or histological type (papillary, solid or mixed). It appears that styrene induces an increase in the number of lung tumors seen spontaneously in CD-1 mice.

Calculations show substantial serial engagement of T cell receptors.

The serial engagement model provides an attractive and plausible explanation for how a typical antigen presenting cell, exhibiting a low density of peptides recognized by a T cell, can initiate T cell responses. If a single peptide displayed by a major histocompatibility complex (MHC) can bind, sequentially, to different T cell receptors (TCR), then a few peptides can activate many receptors. To date, arguments supporting and questioning the prevalence of serial engagement have centered on the down-regulation of TCR after contact of T cells with antigen presenting cells. Recently, the existence of serial engagement has been challenged by the demonstration that engagement of TCR can down-regulate nonengaged bystander TCR. Here we show that for binding and dissociation rates that characterize interactions between T cell receptors and peptide-MHC, substantial serial engagement occurs. The result is independent of mechanisms and measurements of receptor down-regulation. The conclusion that single peptide-MHC engage many TCR, before diffusing out of the contact region between the antigen-presenting cell and the T cell, is based on a general first passage time calculation for a particle alternating between states in which different diffusion coefficients govern its transport.

Pulse-chase analysis of the in vivo assembly of the bacteriophage T4 tail.

The in vivo assembly pathway of the complex tail of bacteriophage T4 virus was determined using pulse-chase analysis as a non-invasive alternative to the in vitro experiments previously used to map assembly. Bacteriophage T4 mutants defective in head assembly were used to infect cultures of Escherichia coli in order to study tail assembly in isolation. Beginning with the onset of late protein synthesis, the cultures were labeled continuously with [(3)H]leucine to normalize against subsequent sample losses. After completed tails had begun to accumulate at a constant rate, the cultures were pulsed with [(35)S]methionine, and then chased. Completed tails were purified at one minute intervals for the next 30 minutes and their proteins separated electrophoretically and counted by liquid scintillation. Total (35)S incorporation into each protein rose and then leveled off as the chase of unlabeled methionine flushed the label through the pools of soluble proteins and assembly intermediates and into completed tails. The inflection point in the sigmoidal (35)S-incorporation curve of each protein marks the maximal uptake of (35)S within that pool just before the effect of the chase becomes apparent and the curve begins to level off. The length of the delay in the apparent chase time reflects the position of that protein in the pathway. The closer the assembly point to the end of the pathway, the sooner the chase appears, revealing the relative order of assembly. As predicted, tail completion proteins such as gp18 (tail sheath) and 19 (tail tube) show the earliest inflection, while those earlier in the pathway take longer to chase. Of the 17 tail proteins analyzed, 14 are in agreement with the established in vitro pathway. The other three, gp15, gp10 and gp53, have helped us to develop a model that offers a plausible explanation for their altered chase times.

The influence of transport on the kinetics of binding to surface receptors: application to cells and BIAcore.

Accurate estimation of biomolecular reaction rates from binding data, when ligands in solution bind to receptors on the surfaces of cells or biosensors, requires an understanding of the contributions of both molecular transport and reaction. Efficient estimation of parameters requires relatively simple models. In this review, we give conditions under which various transport effects are negligible and identify simple binding models that incorporate the effects of transport, when transport cannot be neglected. We consider effects of diffusion of ligands to cell or biosensor surfaces, flow in a BIAcore biosensor, and distribution of receptors in a dextran layer above the sensor surface. We also give conditions under which soluble receptors can be expected to compete effectively with surface-bound receptors.

Inhibitory effects of combinations of HER-2/neu antibody and chemotherapeutic agents used for treatment of human breast cancers.

Previous studies have demonstrated a synergistic interaction between rhuMAb HER2 and the cytotoxic drug cisplatin in human breast and ovarian cancer cells. To define the nature of the interaction between rhuMAb HER2 and other classes of cytotoxic drugs, we applied multiple drug effect/combination index (CI) isobologram analysis to a variety of chemotherapeutic drug/rhuMAb HER2 combinations in vitro. Synergistic interactions at clinically relevant drug concentrations were observed for rhuMAb HER2 in combination with cisplatin (CI=0.48, P=0.003), thiotepa (CI=0.67, P=0.0008), and etoposide (CI=0.54, P=0.0003). Additive cytotoxic effects were observed with rhuMAb HER2 plus doxorubicin (CI=1.16, P=0.13), paclitaxel (CI=0.91, P=0.21), methotrexate (CI=1.15, P=0.28), and vinblastine (CI=1.09, P=0.26). One drug, 5-fluorouracil, was found to be antagonistic with rhuMAb HER2 in vitro (CI=2.87, P=0.0001). In vivo drug/rhuMAb HER2 studies were conducted with HER-2/neu-transfected, MCF7 human breast cancer xenografts in athymic mice. Combinations of rhuMAb HER2 plus cyclophosphamide, doxorubicin, paclitaxel, methotrexate, etoposide, and vinblastine in vivo resulted in a significant reduction in xenograft volume compared to chemotherapy alone (P<0.05). Xenografts treated with rhuMAb HER2 plus 5-fluorouracil were not significantly different from 5-fluorouracil alone controls consistent with the subadditive effects observed with this combination in vitro. The synergistic interaction of rhuMAb HER2 with alkylating agents, platinum analogs and topoisomerase II inhibitors, as well as the additive interaction with taxanes, anthracyclines and some antimetabolites in HER-2/neu-overexpressing breast cancer cells demonstrates that these are rational combinations to test in human clinical trials.

The acute, genetic, developmental, and inhalation toxicology of 1,1,1,3,3-pentafluoropropane (HFC 245fa).

1,1,1,3,3-Pentafluoropropane (HFC 245fa) is a volatile, low boiling liquid. It was inactive in a reverse mutation (Ames) assay using five strains of Salmonella typhimurium and one strain of Escherichia coli. It was also inactive in an in vivo mouse micronucleus assay with exposures of 101,000 ppm. In a chromosome aberration study with human lymphocytes, some activity was seen when cell cultures were exposed to atmospheres of 30% v/v or higher for 24 h without metabolic activation. No activity was seen in assays using less than 30% v/v or exposure times of less than 24 h. No activity was seen in the presence of metabolic activation even with exposures of 70%. It was not toxic by the dermal route. There was no mortality or significant signs of toxicity when rats and mice were given 4- h exposures to levels of 203,000 ppm or 101,000 ppm of HFC 245fa, respectively. In a cardiac sensitization study with dogs involving intravenous administration of epinephrine, the no observed effect level (NOEL) was 34,000 ppm and the threshold for a response was 44,000 ppm. In a rat inhalation, developmental toxicity study, a slight reduction in pup weight was seen at 50,000 ppm, but not at 10,000 ppm. There were no developmental effects at any level. A series of three inhalation toxicity studies were conducted. All involved daily 6-h exposures up to 50,000 ppm. The first study involved 14 consecutive snout-only exposures. There were no treatment-related effects on body weight, survival, or histologic parameters. BUN, GPT, and GOT levels frequently were elevated compared to controls , whereas cholesterol levels tended to be lower. The second study involved 28 consecutive whole-body exposures. Again, there were no treatment related effects on body weight, survival, or histological parameters. Urine volume was increased. Increases were also seen in several red blood cell parameters. These may be related to partial dehydration. Increases were seen in BUN levels and alkaline phosphatase (AP), GPT, GOT and CPK activities, primarily in rats exposed at 10,000 and 50,000 ppm. Urinary fluoride levels were also elevated in an exposure- related pattern. In the third study, whole-body exposures were conducted 5 days per week for 13 weeks. There were no treatment-related effects on survival, clinical observations, body weight gain, or food consumption. Urine volumes were increased, urinary fluoride levels were elevated, and increases were seen in red blood cell counts, and related parameters and increases were seen in AP, GOT, GPT and CPK activities. These effects were seen in the 10,000 and 50,000 ppm exposure level groups. Histopathologic examination did not show any effects on the kidney, liver, or lungs. There was an increased incidence of myocarditis in all animals exposed at 50,000 ppm and the majority exposed at 10,000 ppm. It was described as mild. Based on these findings, 2000 ppm appears to be a no observed adverse effect level.

The bacteriophage T4 DNA packaging apparatus targets the unexpanded prohead.

During the morphogenesis of the bacteriophage T4 capsid, a conformational change of the major head shell protein, gene product (gp) 23, causes a 50% increase in capsid volume. This expansion is required to accept the full length chromosome and, therefore, must precede the completion of packaging. The expanded shell is thinner and more stable than its precursor, and can bind accessory proteins which further stabilize it. In phages lambda, T3, T7 and P22, expansion occurs during DNA packaging. However, in T4, expanded capsids can package DNA in vitro and expansion occurs in cells infected with packaging-defective mutants, raising the possibility that expansion and packaging are not coupled. Proteolytically mature gp23 (gp23*) in unexpanded proheads is sensitive to chymotrypsin cleavage at Phe154-Ser155, creating a 38 kDa peptide, while gp23* in expanded capsids is refractory to the protease. We used an expansion assay based on this protease sensitivity to determine the expansion status of capsids isolated from various packaging-defective mutants with the goal of determining whether packaging and expansion are normally linked. In infections at 20 degrees C, mutants in the packaging enzymes gp16 and gp17 fail to expand. However, in gene 49(-) mutants, which initiate packaging but fail to complete it, expansion is complete. Thus, packaging drives expansion, and the unexpanded prohead is the substrate for the packaging reaction. We also show that expansion observed in 16(-) and 17(-) infections at 37 degrees C is linked to aberrant packaging. Capsids produced at 15 minutes, when no packaging can be detected, never expand. However, by 35 minutes when aberrant packaging begins, so does expansion of freshly made capsids. Thus in all cases now examined, expansion is only observed in vivo when DNA packaging is also occurring, indicating that these two processes are coupled.

Capsid expansion follows the initiation of DNA packaging in bacteriophage T4.

Most bacteriophages undergo a dramatic expansion of their capsids during morphogenesis. In phages lambda, T3, T7 and P22, it has been shown that expansion occurs during the packaging of DNA into the capsid. The terminase-DNA complex docks with the portal vertex of an unexpanded prohead and begins packaging. After some of the DNA has entered, the major head protein undergoes a conformational change that increases both the volume and stability of the capsid. In phage T4, the link between packaging and expansion has not been established. We explored the possibility of such a connection using a pulse-chase protocol and high resolution sucrose gradient analysis of capsid intermediates isolated from wild-type T4-infected cells. We show that the first particle appearing after the pulse is an unexpanded prohead, which can be isolated in vitro as the ESP (empty small particle). The next intermediate to appear is also unexpanded, but contains DNA. This new intermediate, the ISP (initiated small particle), can also be isolated on agarose gels, permitting confirmation of both its expansion state and DNA content ( approximately 10 kbp). It appears, therefore, that >/=8% of the T4 genome enters the head shell prior to expansion. Following packaging of an undetermined amount of DNA, the capsid expands, producing the ILP (initiated large particle), which is finally converted to a full head upon the completion of packaging. An expanded, empty prohead, the ELP (empty large particle), was also observed during 37 degrees C infections, but failed to mature to phage during the chase. Thus the ELP is unlikely to be an intermediate in normal head assembly. We conclude by suggesting that studies on assembly benefit from an emphasis on the processes involved, rather than on the structural intermediates which accumulate if these processes are interrupted.

Chronic toxicity/oncogenicity study of styrene in CD rats by inhalation exposure for 104 weeks.

Groups of 70 male and 70 female Charles River CD (Sprague-Dawley-derived) rats were exposed whole body to styrene vapor at 0, 50, 200, 500, or 1000 ppm 6 h/day 5 days/week for 104 weeks. The rats were observed daily, body weights and food and water consumption were measured periodically, and a battery of hematologic and clinical pathology examinations was conducted at weeks 13, 26, 52, 78, and 104. Nine or 10 rats per sex per group were necropsied after 52 weeks of exposure and the remaining survivors were necropsied after 104 weeks. Control and high-exposure rats received a complete histopathologic examination, while target organs, gross lesions, and all masses were examined in the lower exposure groups. Styrene had no effect on survival in males, but females exposed to 500 or 1000 ppm had a dose-related increase in survival. Levels of styrene in the blood at the end of a 6-h exposure during week 95 were proportional to exposure concentration. Levels of styrene oxide in the blood of rats exposed to 200 ppm or greater styrene were proportional to styrene exposure concentration. There were no changes of toxicologic significance in hematology, clinical chemistry, urinalysis, or organ weights. Males exposed to 500 or 1000 ppm gained less weight than the controls during the first year and maintained the difference during the second year. Females exposed to 200, 500, or 1000 ppm gained less weight during the first year; those exposed to 500 or 1000 ppm continued to gain less during months 13-18. Styrene-related non-neoplastic histopathologic changes were confined to the olfactory epithelium of the nasal mucosa. There was no evidence that styrene exposure caused treatment-related increases of any tumor type in males or females or in the number of tumor-bearing rats in the exposed groups compared to controls. In females, there were treatment-related decreases in pituitary adenomas and mammary adenocarcinomas. Based on an overall evaluation of eight oncogenicity studies, there is clear evidence that styrene does not induce cancer in rats.

Duration of anthelmintic efficacy of doramectin and ivermectin injectable solutions against naturally acquired nematode infections of cattle.

A comparison of persistent efficacy of doramectin injectable (D) and ivermectin injectable (I) was investigated under field conditions with treated permanent principal (PP) and interval-grazed principal (IGP) calves. The experiment was initiated on October 13, 1992 (day 0). Cattle used were crossbred beef heifers of 185 kg average weight and 8 to 10 months old. By random allotment, 66 calves were divided into two groups of 15 PP-D and PP-I calves for each treatment and two groups of 15 IGP-D and IGP-I calves for each treatment. Three extra or replacement calves were allotted for each group. Permanent principal calves in three replicates of five cattle per treatment grazed continuously on nematode-contaminated replicate pastures from day 0 to day 70. At 2-week intervals, i.e., days 0 to 14, 14 to 28, 28 to 42, 42 to 56 and 56 to 70, one IGP-D and one IGP-I calf was grazed with each of the respective PP-D and PP-I calf replicates and necropsied 21 days after removal from pasture. All respective PP calves and IGP calves were treated with doramectin at 200 micrograms kg-1 or ivermectin at 200 micrograms kg-1 by s.c. injection on day 0. After the day 0-14 interval, all IGP-D calves had zero egg counts. From the day 14-28 interval through the next three grazing intervals, the arithmetic mean egg counts of IGP-D calves were 18, 90, 281 and 31; those of IGP-I calves were 30, 226, 74 and 185. This suggested a persistence effect of approximately 2 to 4 weeks. In PP-D calves, egg counts reached a mean maximum at day 56 of only five eggs per gram, while counts of PP-I calves reached a peak of 40 on day 42. From the day 14-28 interval and through all subsequent intervals, arithmetic mean total worm counts from IGP-I calves were 58 to 73% greater than those in IGP-D tracers. A maximal total worm count of 4159 was observed in IGP-D calves of the day 42-56 interval; total worm counts in IGP-I calves from the day 14-28 interval through the day 42-56 interval were: 5420, 6739 and 9979, respectively. Haemonchus and Cooperia were higher in prevalence than Ostertagia in both treatments. Results of PP-D egg counts and total worm burdens in IGP-I calves indicated a high level of doramectin persistent activity for approximately 4 to 5 weeks and an advantage over persistence activity of ivermectin.

A comparison of the efficacy of two treatments of doramectin injectable, ivermectin injectable and ivermectin pour-on against naturally acquired gastrointestinal nematode infections of cattle during a winter-spring grazing season.

Four groups of 18 crossbred beef steer calves (three replicates of six per group) were used to compare persistent efficacy of doramectin injectable, ivermectin injectable and ivermectin pour-on against naturally acquired infections of gastrointestinal nematodes during winter-spring grazing in Louisiana. The experiment was initiated on January 11. Treatments administered on Day 0 and again on April 5 (Day 84, 12-week interval) were: Group 1, untreated controls (CONT); Group 2, doramectin (DOR) at 200 micrograms/kg, s.c. injection; Group 3, ivermectin (IVM-INJ) at 200 micrograms/kg, s.c. injection; Group 4, ivermectin pour-on (IVM-PO) at 500 micrograms/kg, back midline. The cattle were weighed and fecal samples (for egg counts and for culture-larval identification) were collected at regular intervals throughout the 161 day experiment. In the interval between Day 0 and 84, arithmetic mean egg counts of the CONT group averaged about 890 eggs per gram, but then decreased markedly between Days 119 and 126, and remained at a lower plane for the remainder of the experiment. From Day 28 to 56, egg counts of the DOR group were consistently lower (P < 0.05) than those of controls and both IVM-treated groups. Egg counts of the DOR group were always lowest after the second treatment, but differed (P < 0.05) only from IVM-PO counts between Days 119 and 140 (35 and 56 days after the second treatment). Ostertagia was the predominant genus, followed by Cooperia in all four groups. Oesophagostomum, Trichostrongylus, Haemonchus, and Bunostomum were other genera identified. Bodyweights of the DOR group remained significantly greater (P < 0.05) than those of all other groups from Day 112 through the end of the experiment. Total gains for the CONT, DOR, IVM-INJ, and IVM-PO groups were 96, 159, 147, and 150 kg, respectively; treated groups were significantly (P < 0.05) greater than CONT, but differences among treated groups was not significant (P > 0.05).

Twenty-eight-day repeated-dose inhalation exposure of rats to diethylene glycol monoethyl ether.

This study was carried out to provide information on the effects of inhalation of diethylene glycol monoethyl ether, a substance used in industry which may be accidentally inhaled by man. Sprague-Dawley CD rats were exposed by inhalation to a test atmosphere containing diethylene glycol monoethyl ether in a nose-only exposure system for 6 hr a day, 5 days a week for 28 days. Mean exposure levels were 0. 09, 0.27, and 1.1 mg/liter. At the two lowest exposure levels the test substance was present entirely as vapor, but at the highest exposure level the test atmosphere was approximately equally divided by mass into respirable droplets (aerosol) and vapor. A comprehensive battery of toxicological evaluations including food consumption, body weight, clinical signs, hematology, and biochemistry revealed no evidence of a systemic effect of exposure. Histopathological examination showed changes indicative of mild nonspecific irritation in the upper respiratory tract of rats exposed at the two highest exposure levels. These changes consisted of foci of necrosis in the ventral cartilage of the larynx of rats exposed at 0.27 or 1.1 mg/liter and an increase in eosinophilic inclusions in the olfactory epithelium of the nasal mucosa of rats exposed at 1.1 mg/liter. The no observed adverse effect level for systemic effects was 1.1 mg/liter and the no observed adverse effect level for signs indicative of mild nonspecific irritation of the upper respiratory tract was 0.09 mg/liter.