Effects of serial anesthesia using ketamine or ketamine/medetomidine on hematology and serum biochemistry values in rhesus macaques (Macaca Mulatta)

Background  This study aimed at determining the cumulative effect of daily anesthesia, using two drug regimens, over hematological and biochemical parameters.
Methods  Blood samples were obtained from rhesus monkeys 20 minutes after intramuscular administration of ketamine or ketamine/medetomidine combination for three consecutive days and results were evaluated to determine their effect on hematological and serum biochemistry values. Statistical significance of drug, day, and interaction of these two variables were evaluated.
Results  Drug effect resulted in a dramatic increase of aspartate aminotransferase and creatine kinase values. Day effect resulted in decreases of RBC, HCT, Hgb, and alkaline phosphatase but an increase of other biochemical parameters evaluated. The drug/day interaction effect was found to be –significant for RBC, platelets, aspartate aminotransferase, alanine aminotransferase, and creatine kinase values.
Conclusion  The results of our study suggest a cumulative effect of serial anesthesia and should be an important consideration when interpreting hematology and serum biochemistry in rhesus macaques.     

Bioturbation in a declining oxygen environment, in situ observations from Wormcam

Bioturbation, the displacement and mixing of sediment particles by fauna or flora, facilitates life supporting processes by increasing the quality of marine sediments. In the marine environment bioturbation is primarily mediated by infaunal organisms, which are susceptible to perturbations in their surrounding environment due to their sedentary life history traits. Of particular concern is hypoxia, dissolved oxygen (DO) concentrations ≤2.8 mg l(-1), a prevalent and persistent problem that affects both pelagic and benthic fauna. A benthic observing system (Wormcam) consisting of a buoy, telemetering electronics, sediment profile camera, and water quality datasonde was developed and deployed in the Rappahannock River, VA, USA, in an area known to experience seasonal hypoxia from early spring to late fall. Wormcam transmitted a time series of in situ images and water quality data, to a website via wireless internet modem, for 5 months spanning normoxic and hypoxic periods. Hypoxia was found to significantly reduce bioturbation through reductions in burrow lengths, burrow production, and burrowing depth. Although infaunal activity was greatly reduced during hypoxic and near anoxic conditions, some individuals remained active. Low concentrations of DO in the water column limited bioturbation by infaunal burrowers and likely reduced redox cycling between aerobic and anaerobic states. This study emphasizes the importance of in situ observations for understanding how components of an ecosystem respond to hypoxia.     

Modeling the Effect of Hypoxia on Macrobenthos Production in the Lower Rappahannock River,Chesapeake Bay,USA

Hypoxia in Chesapeake Bay has substantially increased in recent decades, with detrimental effects on macrobenthic production; the production of these fauna link energy transfer from primary consumers to epibenthic and demersal predators. As such, the development of accurate predictive models that determine the impact of hypoxia on macrobenthic production is important. A continuous-time, biomass-based model was developed for the lower Rappahannock River, a Bay tributary prone to seasonal hypoxia. Phytoplankton, zooplankton, and macrobenthic state variables were modeled, with a focus on quantitatively constraining the effect of hypoxia on macrobenthic biomass. This was accomplished through regression with Z'': a sigmoidal function between macrobenthic biomass and dissolved oxygen concentration, derived using macrobenthic data collected from the Rappahannock River during the summers of 2007 and 2008, and applied to compute hypoxia-induced mortality as a rate process. The model was verified using independent monitoring data collected by the Chesapeake Bay Program. Simulations showed that macrobenthic biomass was strongly linked to dissolved oxygen concentrations, with fluctuations in biomass related to the duration and severity of hypoxia. Our model demonstrated that hypoxia negatively affected macrobenthic biomass, as longer durations of hypoxia and greater hypoxic severity resulted in an increasing loss in biomass. This exercise represents an important contribution to modeling anthropogenically impacted coastal ecosystems, by providing an empirically constrained relationship between hypoxia and macrobenthic biomass, and applying that empirical relationship in a mechanistic model to quantify the effect of the severity, duration, and frequency of hypoxia on benthic biomass dynamics.     

Use of organic modifiers to enhance chiral selectivity in capillary electrophoresis

Summary Using capillary electrophoresis, the enantiomers of a number of dansyl amino acids were resolved using native-cyclodextrin. The neutral chiral host resolved analytes possessing a negative charge at pH 9, the conditions employed in this study. Organic modifiers added to the running buffer were particularly adept at enhancing chiral recognition between the guest and host molecule in capillary electrophoresis. This work examined the effects of methanol, dimethylformamide, and acetonitrile on the resolution, migration time, and efficiency of twelve dansyl amino acids. Examples are given of the separation of racemic dansyl amino acids utilizing this technique and conditions necessary to achieve enantioselectivity.     

A comparison of the effects of prenatal exposure of CD‐1 mice to three imidazolium‐based ionic liquids

BACKGROUND: Ionic liquids (ILs; salts with melting points below 100°C) exhibit wide liquid ranges, non‐flammability, and thermal stability among other properties. These unique salts are best known as “green” alternatives to traditional volatile organic solvents, which are utilized in both academia and industry. Our current study compares the developmental toxicity potential of three representative ionic liquids, with various chain lengths: 1‐ethyl‐3‐methylimidazolium chloride ([C₂mim]Cl), 1‐butyl‐3‐methylimidazolium chloride ([C₄mim]Cl), and 1‐decyl‐3methylimidazolium chloride ([C₁₀mim]Cl). METHODS: From gestation days (GD) 6‐16, mated CD‐1 mice were orally dosed with one of the following: 1,000, 2,000, or 3,000 mg/kg/day [C₂mim]Cl; 113, 169, or 225 mg/kg/day [C₄mim]Cl; 50, 75, or 100 mg/kg/day [C₁₀mim]Cl; or the vehicle only. Dams were sacrificed on GD 17, and their litters were examined for adverse effects. RESULTS: Fetal weight was significantly decreased in the two highest dosage groups exposed to [C₄mim]Cl and [C₁₀mim]Cl in comparison with their controls, but the [C₂mim]Cl treated groups were not affected. An apparent teratogenic effect was associated with both [C₄mim]Cl and [C₁₀mim]Cl, as the offspring exhibited certain uncommon morphological defects. However, the incidences of malformations were low and no correlation between incidence and dosage could be made. No morphological defects were observed in any of the [C₂mim]Cl‐treated groups, despite maternal morbidity at the highest dosage level. CONCLUSIONS: This study indicates that [C₄mim]Cl and [C₁₀mim]Cl may have adverse effects on development at high maternal exposures and strongly supports the supposition that the toxicity of imidazolium‐based ILs is influenced by alkyl chain length. Birth Defects Res (Part B) 89:233–238, 2010. © 2010 Wiley‐Liss, Inc.     

Effects of housing density on Long Evans and Fischer 344 rats

At many breeding facilities, rats are housed at relatively high densities until they are 5 weeks old, at which point they are either shipped for research or rehoused at standard cage densities according to weight. The authors carried out a pilot study in Long Evans and in Fischer 344 rats to investigate whether continuing to house rats at high densities (24 in(2) floor space per rat) past the age of 5 weeks, through puberty and into adulthood would alter behavioral or physiological parameters compared with raising rats at standard densities (about 72 in(2) floor space per rat). After rats reached puberty, the authors rehoused them with unfamiliar cagemates. The researchers evaluated clinical and behavioral signs of stress, weight, blood glucose concentration, white blood cell count and serum corticosterone concentration. Overall, cage density had little effect on the parameters measured, though gender seemed to affect stress in Long Evans rats. The results suggest that rats of these strains can be raised at the higher densities tested until any age and regrouped with unfamiliar cagemates without compromising rats' welfare or subsequent experimental data.     

Evaluation of a Red Cell Agglutination Test for Detection of Australia Antigen (HB Ag)

An investigational red cell agglutination (RCA) test was evaluated for sensitivity in detecting and titering hepatitis B antigen (HB Ag) in comparison with two counterelectrophoresis (CEP) systems and a solid-phase radioimmunoassay (RIA). The RCA procedure was found to be significantly more sensitive than the CEP methods and compares favorably in sensitivity with the solid-phase RIA, detecting even lower concentrations of the HB Ag. Since the RCA test can be completed in 2 to 3 h and requires relatively inexpensive equipment, it offers a highly sensitive and rapid procedure suitable for use in blood banks to screen donors or detect low levels of antigen in serum of patients.     

Effects of Pre- and Postnatal Exposure to Chromium Picolinate or Picolinic Acid on Neurological Development in CD-1 Mice

Chromium picolinate, Cr(pic)3, a popular dietary supplement marketed as an aid in fat loss and lean muscle gain, has also been suggested as a therapy for women with gestational diabetes. The current study investigated the effects of maternal exposure to Cr(pic)3 and picolinic acid during gestation and lactation on neurological development of the offspring. Mated female CD-1 mice were fed diets from implantation through weaning that were either untreated or that contained Cr(pic)3 (200 mg kg(-1) day(-1)) or picolinic acid (174 mg kg(-1) day(-1)). A comprehensive battery of postnatal tests was administered, including a modified Fox battery, straight-channel swim, open-field activity, and odor-discrimination tests. Pups exposed to picolinic acid tended to weigh less than either control or Cr(pic)3-exposed pups, although the differences were not significant. Offspring of picolinic acid-treated dams also appeared to display impaired learning ability, diminished olfactory orientation ability, and decreased forelimb grip strength, although the differences among the treatment groups were not significant. The results indicate that there were no significant effects on the offspring with regard to neurological development from supplementation of the dams with either Cr(pic)3 or picolinic acid.     

Comparison of the potential for developmental toxicity of prenatal exposure to two dietary chromium supplements, chromium picolinate and [Cr3O(O2CCH2CH3)(6(H2O)3]+, in mice

BACKGROUND: Chromium(III) is generally thought to be an essential trace element that allows for proper glucose metabolism. However, chromium(III) picolinate, Cr(pic)₃, a popular dietary supplement form of chromium, has been shown to be capable of generating hydroxyl radicals and oxidative DNA damage in rats. The cation [Cr₃O(O₂CCH₂CH₃)₆(H₂O)₃]⁺, Cr3, has been studied as an alternative supplemental source of chromium. It has been shown to increase insulin sensitivity and lower glycated hemoglobin levels in rats, making it attractive as a potential therapeutic treatment for gestational diabetes. To date, no studies have been published regarding the safety of Cr3 supplementation to a developing fetus. METHODS: From gestation days (GD) 6–17, mated CD‐1 female mice were fed diets delivering either 25 mg Cr/kg/day as Cr(pic)₃, 3.3 or 26 mg Cr/kg/day as Cr3, or the diet only to determine if Cr3 could cause developmental toxicity. Dams were sacrificed on GD 17, and their litters were examined for adverse effects. RESULTS: No signs of maternal toxicity were observed. No decrease in fetal weight or significantly increased incidence of skeletal defects was observed in the Cr3 or Cr(pic)₃ exposed fetuses compared to the controls. CONCLUSION: Maternal exposure to either Cr(pic)₃ or Cr3 at the dosages employed did not appear to cause deleterious effects to the developing offspring in mice. Birth Defects Res (Part B), 80:1–5, 2007. © 2007 Wiley‐Liss, Inc.     

Developmental toxicity of 1,6-hexamethylene diisocyanate (HDI) in the Sprague-Dawley rat

BACKGROUND: 1,6-Hexamethylene diisocyanate (HDI), a widely used chemical in commercial polyurethane manufacture, has been shown to affect the respiratory tract of experimental animals. However, its potential to affect neonatal development, particularly after inhalation exposure, is less well described. The present study was conducted to assess the developmental toxicity of HDI. METHODS: Gravid Sprague-Dawley rats were exposed to concentrations of 0, 0. 005, 0.050, or 0.300 ppm HDI via inhalation (whole-body exposure) on days 0-19 of gestation. Maternal toxicity, as demonstrated by clinical signs and changes in body weight gain during gestation, was characterized. Dams were sacrificed on gestation day 20, at which time fetuses were removed by cesarean section, the uterus was examined, and a gross maternal necropsy was performed. Maternal evaluation also included lung weight and a detailed histopathologic assessment of the nasal turbinates, larynx, trachea, and lungs. All fetuses were evaluated for external anomalies. Approximately one-half of each litter was examined for visceral effects, the other half underwent a skeletal (bone and cartilage) examination. RESULTS: Maternal toxicity was demonstrated in the 0.300- and, to a lesser extent, in the 0.050-ppm exposure groups. No maternal effects were noted in the 0.005-ppm group. Test compound-related maternal effects were restricted to histopathological findings and included acanthosis, hyperkeratosis, inflammation of the nasal turbinates, and, more seriously, degeneration of the olfactory epithelium. No pathological alterations were noted in the larynx, trachea, or lungs in any dose group. No test compound-related effects were observed on any reproductive parameters, or any embryonic endpoints, including pre/postimplantation loss and resorption. There were no effects on litter size or the number of fetuses per implantation site and no effects on fetal or placental weights were observed. No test compound-related fetal external, visceral, or skeletal findings were observed. No effect on the fetal or litter incidence of total malformations or variations was observed, and there was no difference in the incidence of malformations between males and females. CONCLUSIONS: Administered as described in this study, 1, 6-HDI produced maternal effects (nasal turbinate histopathology) at concentrations of 0.050 and 0.300 ppm with no developmental toxicity observed at any concentration.