Effect of immunologic solutions on sows and gilts on time to stability, and production losses in breeding herds infected with 1-7-4 PRRSv.

Porcine reproductive and respiratory syndrome virus (PRRSv) is an economically significant swine pathogen causing production losses in the global swine industry. Clinical impact depends on many factors including the virus itself. One method to sub-type PRRSv is using restriction fragment length polymorphism (RFLP). The RFLP pattern 1-7-4 emerged within the United States swine industry in 2014 and has become prevalent since then. This was a field study that prospectively followed 1-7-4-infected breeding herds (n=107) and compared time to stability (TTS), time to baseline production (TTBP) and total loss per 1000 sows between herds using modified-live virus vaccine (MLV) on sows and gilts (MLV-MLV), MLV on sows and MLV in addition to field virus exposure on gilts (MLV-MLV/FVE) or not deliberately exposing sows or gilts to PRRSv (Natural-Natural). Analyses were done in SAS 9.4 and results were adjusted by selected co-variates (duration of herd closure, number of previous PRRSv outbreaks of last 3 years, weaning frequency/week, gilt development unit location, herd size and production system). Survival analysis was conducted on TTS and TTBP and regression analysis on total loss. Herds in the Natural-Natural group achieved TTS and TTBP before other herds. Herds in the MLV-MLV/FVE had the longest TTS and TTBP. The total loss was numerically least in MLV-MLV herds (1194 pigs/1000 sows) compared to MLV/MLV-FVE (1810/1000 sows) and Natural-Natural (2671/1000 sows). This study provided additional information to assist veterinarians deciding between methods of exposure to manage PRRSv infection from breeding herds.

Hydroxyzine intoxication in a 13-month-old child.

A case of hydroxyzine toxicity following accidental ingestion in a 13-month old female infant has been presented. A plasma hydroxyzine concentration 8.5 hours after the acute ingestion was 102.7 micrograms/ml and toxicity was manifested primarily by generalized seizures and sinus tachycardia. General supportive care and seizure control with physostigmine resulted in complete recovery within 72 hours. This case represents the first documented report of hydroxyzine toxicity following acute ingestion in a child.

Oral pharmacokinetics of carbamazepine in dogs from commercial tablets and a cyclodextrin complex.

The extent of absorption of carbamazepine from a 2-hydroxypropyl-beta-cyclodextrin/carbamazepine complex was significantly greater and the rate of absorption was faster when compared with an immediate-release carbamazepine tablet in the dog. Six dogs were dosed orally in a two-way crossover study in which the tablet was compared with an equivalent dose of the complex in solution. The area under the curve of concentration versus time for the complex was 5.6 times greater than the tablet, whereas the mean time to reach maximum concentration for the tablet was 1.4 hours versus 0.5 hours for the complex. The complex, therefore, had a greater rate and extent of absorption. A rapidly acting and better absorbed carbamazepine product has the potential to decrease the daily dose of carbamazepine, increase its utility as emergency treatment of epileptic seizures, and provide an acceptable alternative dosage form in patients who are unable to swallow tablets.

Biodisposition of theophylline. I. Genetic variation in inbred mice.

[8-14C]Theophylline was infused into mice with an osmotic minipump. Theophylline and its metabolites were separated from urine, blood, and feces by high-performance liquid chromatography and the radioactivity was determined by liquid-scintillation counting. The strains examined were SJL, DBA/2, C57BL/6, A/J, C3H/HeJ, AKR, SWR, and BALB/c. The theophylline clearance ranged from 479 +/- 30 ml/kg/hr in the A/J strain to 845 +/- 58 ml/kg/hr in the SJL strain. The total clearance in the A/J strain was signficantly different (p < 0.05) from that in the BALB/c, C57BL/6, and SJL strains. The metabolic pathway primarily responsible for this variation was the production of 1,3-dimethyluric acid.

Biodisposition of theophylline. II. Effect of aromatic hydrocarbon treatment in mice.

The effect of polycyclic aromatic hydrocarbons on theophylline clearance was examined in six inbred mice strains. The DBA/2 and SJL strains were nonresponsive to this treatment, whereas C3H/HeJ, C57BL/6, BALB/c, and A/J strains were responsive. In the responsive strains, the total body clearance increased by a factor of 2.3 to 3.4, apparently due to a general induction of all metabolic pathways. The production of 1,3-dimethyluric acid was not increased in the C57BL/6 strain. The variation in induction among responsive strains appeared to be primarily associated with the increase in the oxidation to 1,3-dimethyluric acid.

Absence of an effect of t-alleles on epididymal and testicular metabolism of 5-3H-uridine in mice.

Earlier reports have suggested that the epididymis secretes RNA, and that the amount of these secretions varies among T/t6, T/t12 and C57BR mice. In this report, the epididymal perfusate, the total uptake and incorporation of 5-3H-uridine into the epididymis and testicle were examined. Mice examined were T/t6 and +/+ (B6D2F1) and their F1 hybrids, and T/t12 and +/+ (Swiss Webster) and their F1 hybrids. No t-related or age-related effect was seen. However, the F1 hybrids of T/t6 and +/+ (B6D2F1) were significantly lower than the parents at the 4-hour interval.

28 s and 18 s ribonucleic acid from mammalian spermatozoa.

The majority of RNA is spermatozoa from the epididymis and ductus deferens of mice was found to be 28 s and 18 s RNA. This RNA was also seen in human ejaculated spermatozoa. Our evidence indicates that little or none of the 28 s and 18 s RNA is transcribed in the maturing mouse spermatozoa and that the majority is synthesized in the primary spermatocyte. This RNA may be necessary to maintain post-meiotic translation during spermatogenesis.

DNA synthetic capabilities of differentiating sperm cells.

Spermatogenic cells separated by velocity sedimentation were analysed by a micro-procedure for differentiation-associated changes in DNA synthetic capabilities. DNA-dependent DNA polymerase activity is maximal in premeiotic and meiotic cells, sequentially declines in progressively more differentiated spermiogenic cells to a minimum value in testicular spermatozoa which is 1/14 of the maximum. No further decrease of activity is observed during the subsequent process of sperm cell maturation and, at the end-differentiated state, the potential of sperm cells for DNA synthesis is demonstrated by the presence of substantial activities of thymidine and thymidylate kinases as well as DNA polymerase activity, as determined by in vitro assay, are polymerase. Although levels of DNA polymerase activity, as determined by in vitro assay, are negatively correlated with the state of differentiation, the findings support the hypothesis that, in this cell system, DNA synthetic enzymes may not be limiting factors in the control of DNA synthesis.

Physiologic considerations in drug absorption from the gastrointestinal tract.

The dynamic interaction between variables within the gastrointestinal tract and the physiochemical properties of a drug in a delivery system determine the rate and extent of absorption of that drug. Among the major physiologic variables are pH, gastric emptying time, and intestinal transit time. Some physicochemical properties of interest include solubility, particle size, and chemical form of the drug. Attributes of the formulation such as controlled-release mechanism, pH sensitivity, and size, shape, and density of the product can also affect absorption. Food has also been reported to influence the absorption from some but not all controlled-release products. As a more thorough understanding of the many factors involved in drug absorption is developed, the formulation of more sophisticated oral drug delivery systems will be possible.

Further evidence for haploid gene expression during spermatogenesis: heterogeneous, poly(A)- containing RNA is synthesized post-meiotically.

Mouse testicular cells labelled in vivo with 3H-uridine for 1 hour were separated into enriched cell populations representing different stages of spermatogenesis by centrifugation in an Elutriator rotor. RNA extracted with phenol and chloroform was sized by electrophoresis on 2.4% acrylamide gels. The percentage of newly synthesized RNA which was not ribosomal RNA (or its precursors) and was not transfer RNA, was higher in early postmeiotic, as compared to late premeiotic, stages. RNA was also extracted from fractionated cells in the presence of guanidinium chloride and the proportion of total 3H-RNA-containing poly(A) sequences was determined by binding to an oligo-(dT)-cellulose column. RNA that bound in 0.5 NaCl was eluted with low salt buffer and reapplied twice more, after heating each time in DMSO to disaggregate any non-poly(A)-containing RNA. The percentage of newly synthesized RNA which contained poly(A) did not decrease in early postmeiotic, as compared to late premeiotic, stages. We suggest that at least some part of the 6-15S 3H-RNA and 3H-poly(A)-containing RNA represents mRNA(s) transcribed postmeiotically in haploid germ cells.

Bioavailability and pharmacokinetics of a new sustained-release potassium chloride tablet.

The bioavailability of a new sustained-release potassium chloride (KCl) tablet, designed for once-a-day dosing, was compared to a KCl elixir using urinary excretion data. The study utilized 25 male volunteers dosed in a crossover design in a dietary/activity-controlled environment. The regimens consisted of a total of 80 mEq of potassium in three equally divided doses of elixir every 6 hr and a single 80-mEq dose using four 20-mEq sustained-release (SR) tablets. The mean time to maximum rate of potassium urinary excretion was 2.2 hr for the first elixir dose and 5.5 hr after the SR tablet (P less than 0.01), thereby supporting the prolonged-release properties of this formulation. After correction for baseline urinary potassium excretion, the mean total 24-hr urinary potassium excretion was 42.18 mEq for the elixir and 40.41 mEq for the SR tablet. The results indicate that the absorption pattern from the SR tablet is equal to three doses of KCl elixir dosed 6 hr apart.

The effect of raising gastric pH with ranitidine on the absorption and elimination of theophylline from a sustained-release theophylline tablet.

Prior to evaluating the effect of ranitidine on theophylline absorption from a sustained-release theophylline tablet, the effect of ranitidine on the time course of gastric pH in 12 healthy subjects was evaluated with an encapsulated radio-telemetry device (Heidelberg capsule). Gastric pH was measured hourly from 7 AM to 1 PM prior to beginning ranitidine treatment at 2 PM (150 mg every 4 hr for eight doses). The next day, pH was again measured hourly from 7 AM to 7 PM. Subjects fasted overnight and remained fasted until lunch at 11 AM. Prior to ranitidine treatment, the mean morning gastric pH remained between 1.5 and 2.2. After lunch, the pH increased to 2.2-2.3. During ranitidine treatment the mean morning gastric pH measurements were 5.5 to 5.8, decreasing after lunch to 3.1 by 4 PM and increasing to 3.9 at 7 PM. One week later the subjects participated in a three-way crossover theophylline bioavailability study receiving at weekly intervals, single doses at 7 AM of (a) 5 x 100-mg immediate-release tablets, (b) 2 x 300-mg sustained-release theophylline tablets, and (c) 2 x 300-mg sustained-release theophylline tablets after ranitidine pretreatment of 150 mg every 4 hr beginning at 2 PM the previous day. The increase in gastric pH with ranitidine had no effect (P greater than 0.05) on the rate and extent of absorption or on the elimination rate of theophylline.