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Journal of the American Association For... Jul 2018The provision of nesting material benefits mice by reducing cold stress, improving feed conversion, increasing litter size, and improving adaptive immunity. The effects...
The provision of nesting material benefits mice by reducing cold stress, improving feed conversion, increasing litter size, and improving adaptive immunity. The effects of toxins are sensitive to environmental changes, and the introduction of novel items can alter results in some toxicologic studies. We hypothesized that nesting material would reduce stress and positively alter immunologic parameters in Crl:CD1(ICR) mice, thus changing typical results from a well-studied immunomodulating drug, cyclophosphamide. A 13-wk study assessed the following treatments in a factorial design (n = 4; 32 cages total): nesting (0 or 10 g) and drug (50 mg/kg cyclophosphamide or 10 mL/kg saline; IP weekly). Detailed examinations and body weights were recorded weekly, and nests were scored twice weekly. Fecal pellets were collected at 0, 4, 6, and 12 wk for analysis of corticosterone metabolites. At study termination, clinical pathology and immune parameters were collected, a necropsy performed, and lymphoid organs and adrenal glands were submitted for histopathology. All expected results due to cyclophosphamide were observed. Nesting reduced the proportion of mice with piloerection, and body weights were highest in saline-nested male mice. No differences in hematology, clinical chemistry, or absolute lymphocyte counts were observed. Corticosterone metabolites in all nested groups were not different from baseline levels but all nonnested groups had higher levels than baseline. Nested cyclophosphamide-treated groups had significantly lower corticosterone levels than nonnested cyclophosphamide-treated groups. This study illustrates that nesting material does not alter the results of a standard toxicology study of cyclophosphamide but alleviates study-related stress and improves mouse welfare.
Topics: Animals; Corticosterone; Cyclophosphamide; Feces; Female; Housing, Animal; Immunosuppressive Agents; Male; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Nesting Behavior; Pregnancy
PubMed: 29976274
DOI: 10.30802/AALAS-JAALAS-17-000114 -
Toxicology Reports 2018A 14-d short-term oral toxicity study in rats evaluated the safety of moringa isothiocyanate-1 (MIC-1)-enriched hydro-alcoholic moringa seeds extract (MSE). Rats (5...
A 14-d short-term oral toxicity study in rats evaluated the safety of moringa isothiocyanate-1 (MIC-1)-enriched hydro-alcoholic moringa seeds extract (MSE). Rats (5 males/5 females per group) were gavaged daily for 14 d with the vehicle control or MSE, at 78 (low), 257 (mid-low), 772 (mid-high), or 2571 (high) mg/kg bw/d, standardized to MIC-1 (30, 100, 300, or 1000 mg/kg bw/d, respectively). Toxicological endpoints included body weight and weight gain, food consumption and feed efficiency, clinical observations, hematology, gross necropsy and histopathology, and relative organ weights. Mortality was only observed in the high dose group animals, both male and female, representing decreases in body weight/weight gain and food consumption/feed efficiency. Irregular respiratory patterns and piloerection were major clinical observations found primarily in the mid-high and high dose group animals. In the high dose group, gastrointestinal distention and stomach discoloration were observed in non-surviving males and females, and degeneration and necrosis of the testicular germinal cells and epididymal cells were also observed in a non-surviving male. Increased liver weights were found in females in the mid-high and high dose groups. Animals in the low and mid-low groups did not exhibit adverse effects of MSE (100 mg/kg bw/d MIC-1). A no observed adverse effect level (NOAEL) of the standardized MSE was determined as 257 mg/kg bw/d providing 100 mg/kg bw/d MIC-1.
PubMed: 29854612
DOI: 10.1016/j.toxrep.2018.02.012 -
Journal of Toxicologic Pathology Jan 2018In this study, we aimed to evaluate changes in the acute toxicity of intraperitoneally administered silver nanoparticles (AgNPs) of varying sizes in BALB/c mice....
In this study, we aimed to evaluate changes in the acute toxicity of intraperitoneally administered silver nanoparticles (AgNPs) of varying sizes in BALB/c mice. Seven-week-old female BALB/c mice were intraperitoneally administered AgNPs measuring 10, 60, or 100 nm in diameter (0.2 mg/mouse) and then sacrificed 1, 3, or 6 h after treatment. In mice administered 10 nm AgNPs, reduced activity and piloerection were observed at 5 h post administration, and lowered body temperature was observed at 6 h post administration, with histopathological changes of congestion, vacuolation, single cell necrosis, and focal necrosis in the liver; congestion in the spleen; and apoptosis in the thymus cortex. These histopathological changes were not evident following administration of either 60 or 100 nm AgNPs. These results suggested that smaller AgNPs, e.g., those measuring 10 nm in diameter, had higher acute toxicity in mice.
PubMed: 29479144
DOI: 10.1293/tox.2017-0043 -
Animal Behaviour Feb 2018In cooperatively breeding species, encounters with intruders may serve multiple functions ranging from reaffirming group territory ranges to facilitating assessments for...
In cooperatively breeding species, encounters with intruders may serve multiple functions ranging from reaffirming group territory ranges to facilitating assessments for additional breeding opportunities. While these distinctive events offer the opportunity to investigate the delicate balance of these social dimensions within animal societies, their unpredictable occurrence makes witnessing and controlling these events in the wild particularly challenging. Here we used a field playback approach to simulate conspecific territorial incursions in cooperatively breeding common marmosets () to distinguish between the three following non-mutually exclusive functions of intergroup encounters in this species of New World primate: territorial defense, mate defense, and assessment of breeding opportunities. For these experiments, we systematically broadcast species-typical long-distance contact calls - phees - commonly used in intergroup interactions from the core and periphery of the groups' territories using either male or female vocalizations. Consistent with a territorial defense hypothesis, a group's reaction was independent of the simulated intruder's sex and the response strength was greater when the playback stimulus was broadcast from the core areas of groups' territories relative to stimulus broadcast from periphery areas. However, sex differences in some facets of their responses suggest that this is not the only potential function for these encounters. Mated males and females started to move first in response to simulated intruders of the opposite sex, suggesting that these events offered opportunities to assess extra-pair breeding opportunities, while the occurrence of females' piloerection towards simulated female intruders is suggestive of mate-guarding. These data provide unique experimental evidence for the theory that excursions by conspecific intruders may serve multiple functions in a cooperatively breeding vertebrate and are reflective of the known complexities of common marmoset sociobiology.
PubMed: 37065636
DOI: 10.1016/j.anbehav.2017.12.009 -
Frontiers in Neuroscience 2017The present study is focused on a review of the current state of investigating music-evoked emotions experimentally, theoretically and with respect to their therapeutic... (Review)
Review
The present study is focused on a review of the current state of investigating music-evoked emotions experimentally, theoretically and with respect to their therapeutic potentials. After a concise historical overview and a schematic of the hearing mechanisms, experimental studies on music listeners and on music performers are discussed, starting with the presentation of characteristic musical stimuli and the basic features of tomographic imaging of emotional activation in the brain, such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), which offer high spatial resolution in the millimeter range. The progress in correlating activation imaging in the brain to the psychological understanding of music-evoked emotion is demonstrated and some prospects for future research are outlined. Research in psychoneuroendocrinology and molecular markers is reviewed in the context of music-evoked emotions and the results indicate that the research in this area should be intensified. An assessment of studies involving measuring techniques with high temporal resolution down to the 10 ms range, as, e.g., electroencephalography (EEG), event-related brain potentials (ERP), magnetoencephalography (MEG), skin conductance response (SCR), finger temperature, and goose bump development (piloerection) can yield information on the dynamics and kinetics of emotion. Genetic investigations reviewed suggest the heredity transmission of a predilection for music. Theoretical approaches to musical emotion are directed to a unified model for experimental neurological evidence and aesthetic judgment. Finally, the reports on musical therapy are briefly outlined. The study concludes with an outlook on emerging technologies and future research fields.
PubMed: 29225563
DOI: 10.3389/fnins.2017.00600 -
Toxicology Reports 2017Bitter orange ( L.) extracts are widely used in dietary supplements and bitter oranges are used in various juices and food products. -Synephrine, the primary active...
Bitter orange ( L.) extracts are widely used in dietary supplements and bitter oranges are used in various juices and food products. -Synephrine, the primary active constituent, comprises approximately 90% of total protoalkaloids. This study, performed per OECD 408 guidance, examined the 90-day subchronic safety/toxicity of an extract standardized to 50% -synephrine at doses of 100, 300 and 1000 mg/kg/day to male and female rats. No adverse effects were observed with respect to any of the observed parameters of clinical signs, functional observations of sensory reactivity, grip strength and motor activity, ophthalmology, body weights, hematology, food consumption, urinalysis, organ weights, as well as gross and microscopic pathology at termination at any of the doses in either sex. Treatment at 1000 mg/kg body weight/day of the extract resulted in non-adverse effects including fully reversible signs of repetitive head burrowing in the bedding material and piloerection for short periods of time in both sexes immediately after administration, which gradually disappeared by treatment day-81. A slight and reversible elevation of BUN and urea levels in male rats, and slight to mild increase in the relative but not absolute heart weights of male and female rats was observed. Based on these results, the no-observed-effect-level (NOEL) for this bitter orange extract standardized to 50% -synephrine was 300 mg/kg, while the no-observed-adverse-effect-level (NOAEL) was 1000 mg/kg. The results indicate a high degree of safety for this bitter orange extract.
PubMed: 29214145
DOI: 10.1016/j.toxrep.2017.11.002 -
Molecular Human Reproduction Aug 2017Is resveratrol able to prevent the lipopolysaccharide (LPS)-induced preterm labor in 15-day pregnant BALB/c mice?
STUDY QUESTION
Is resveratrol able to prevent the lipopolysaccharide (LPS)-induced preterm labor in 15-day pregnant BALB/c mice?
SUMMARY ANSWER
Resveratrol prevented the LPS-induced onset of preterm labor in 64% of the cases and showed anti-inflammatory and tocolytic effects by downregulating COX-2 and iNOS expression and NOS activity, and by changing the uterine prostaglandin and endocannabinoid profiling.
WHAT IS KNOWN ALREADY
Genital tract infections by Gram-negative bacteria are a common complication in human pregnancy and have been shown to increase risk of preterm delivery. Bacterial LPS elicits a strong maternal inflammatory response that results in preterm delivery and fetal death in a murine model endotoxin-induced preterm labor.
STUDY DESIGN, SIZE, DURATION
An in vivo animal study was conducted. On Day 15 of pregnancy, mice received at 8:00 h a dose of vehicle (40% ethanol in saline solution) or resveratrol (3 mg/kg in vehicle) via oral gavage followed by two doses of LPS or vehicle administered intraperitoneally (i.p.), the first one at 10:00 h (0.17 mg/kg in 0.1 ml of sterile saline solution) and the second at 13:00 h (0.5 mg/kg in 0.1 ml of sterile saline solution). The mice were closely observed for any signs of morbidity (piloerection, decreased movement, and diarrhea), vaginal bleeding or preterm delivery. The beginning of preterm delivery was defined by early delivery of the first pup. Normal term labor occurs on Day 19 of gestation.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Time of labor, pregnancy outcome and morphological features were evaluated after LPS and/or resveratrol administration. Uterine stripes were collected 5 h after the last LPS injection and prostaglandin and endocannabinoid profiling was analyzed by mass spectrometry. Nitric oxide synthase (NOS) activity was measured by radioconversion assay. Cyclooxygenase-2 (Cox-2) and 15-hydroxyprostaglandin dehydrogenase (15-Pgdh) mRNA levels were analyzed by RT-PCR whilst the protein expression of inducible nitric oxide synthase (iNOS), COX-1 and COX-2 were studied by western blot.
MAIN RESULTS AND THE ROLE OF CHANCE
In vivo treatment of 15-day pregnant BALB/c mice with resveratrol prevented the LPS-induced preterm birth in 64% of the cases, whereas only 15% of mice with LPS alone escaped preterm birth. Treatment with resveratrol resulted in a reduced NOS activity (P < 0.05) in the uterus of LPS-treated mice. Similarly, resveratrol reduced the expression of LPS-induced pro-inflammatory agents such as iNOS (P < 0.05), COX-2 (P < 0.05), prostaglandin E2 (PGE2) (P < 0.05) and anandamide (AEA) (P < 0.05). Moreover, resveratrol administration resulted in changes in the uterine endocannabinoid profiling altered by LPS.
LARGE SCALE DATA
N/A.
LIMITATIONS, REASONS FOR CAUTION
Since our experimental design involves the use of mice, the extrapolation of the results presented here to humans is limited.
WIDER IMPLICATIONS OF THE FINDINGS
Our findings provide evidence for the tocolytic effects of resveratrol.
STUDY FUNDING AND COMPETING INTEREST(S)
Dr Ana María Franchi was funded by Agencia Nacional para la Promoción Científica y Tecnológica (PICT 2013/0097) and by Consejo Nacional de Investigaciones Científicas y Técnicas (PIP 2012/0061). Dr Heather B. Bradshaw was funded by NIH (DA006668). The authors have no competing interests.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Endocannabinoids; Female; Inflammation; Lipopolysaccharides; Mice, Inbred BALB C; Obstetric Labor, Premature; Pregnancy; Prostaglandins; Protective Agents; Resveratrol; Stilbenes; Uterus
PubMed: 28810692
DOI: 10.1093/molehr/gax036 -
Annals of Indian Academy of Neurology 2017
PubMed: 28615914
DOI: 10.4103/aian.AIAN_427_16 -
Cancer Medicine Jun 2017Erymet is a new therapy resulting from the encapsulation of a methionine gamma-lyase (MGL; EC number 4.4.1.11) in red blood cells (RBC). The aim of this study was to...
Erymet is a new therapy resulting from the encapsulation of a methionine gamma-lyase (MGL; EC number 4.4.1.11) in red blood cells (RBC). The aim of this study was to evaluate erymet potential efficacy in methionine (Met)-dependent cancers. We produced a highly purified MGL using a cGMP process, determined the pharmacokinetics/pharmacodynamics (PK/PD) properties of erymet in mice, and assessed its efficacy on tumor growth prevention. Cytotoxicity of purified MGL was tested in six cancer cell lines. CD1 mice were injected with single erymet product supplemented or not with vitamin B6 vitamer pyridoxine (PN; a precursor of PLP cofactor). NMRI nude mice were xenografted in the flank with U-87 MG-luc2 glioblastoma cells for tumor growth study following five intravenous (IV) injections of erymet with daily PN oral administration. Endpoints included efficacy and event-free survival (EFS). Finally, a repeated dose toxicity study of erymet combined with PN cofactor was conducted in CD1 mice. Recombinant MGL was cytotoxic on 4/6 cell lines tested. MGL half-life was increased from <24 h to 9-12 days when encapsulated in RBC. Conversion of PN into PLP by RBC was demonstrated. Combined erymet + PN treatment led to a sustained Met depletion in plasma for several days with a 85% reduction of tumor volume after 45 days following cells implantation, and a significant EFS prolongation for treated mice. Repeated injections in mice exhibited a very good tolerability with only minor impact on clinical state (piloerection, lean aspect) and a slight decrease in hemoglobin and triglyceride concentrations. This study demonstrated that encapsulation of methioninase inside erythrocyte greatly enhanced pharmacokinetics properties of the enzyme and is efficacy against tumor growth. The perspective on these results is the clinical evaluation of the erymet product in patients with Met starvation-sensitive tumors.
Topics: Animals; Antineoplastic Agents; Carbon-Sulfur Lyases; Cell Line, Tumor; Cell Proliferation; Cell Survival; Drug Delivery Systems; Erythrocytes; Humans; Male; Methionine; Mice, Nude; Neoplasms; Pyridoxal Phosphate; Pyridoxine; Recombinant Proteins; Tumor Burden
PubMed: 28544589
DOI: 10.1002/cam4.1086 -
Social Cognitive and Affective... Aug 2017It is a common experience-and well established experimentally-that music can engage us emotionally in a compelling manner. The mechanisms underlying these experiences...
It is a common experience-and well established experimentally-that music can engage us emotionally in a compelling manner. The mechanisms underlying these experiences are receiving increasing scrutiny. However, the extent to which other domains of aesthetic experience can similarly elicit strong emotions is unknown. Using psychophysiology, neuroimaging and behavioral responses, we show that recited poetry can act as a powerful stimulus for eliciting peak emotional responses, including chills and objectively measurable goosebumps that engage the primary reward circuitry. Importantly, while these responses to poetry are largely analogous to those found for music, their neural underpinnings show important differences, specifically with regard to the crucial role of the nucleus accumbens. We also go beyond replicating previous music-related studies by showing that peak aesthetic pleasure can co-occur with physiological markers of negative affect. Finally, the distribution of chills across the trajectory of poems provides insight into compositional principles of poetry.
Topics: Adult; Brain; Electromyography; Emotions; Esthetics; Female; Humans; Magnetic Resonance Imaging; Male; Music; Nucleus Accumbens; Poetry as Topic; Psychophysiology; Reward; Young Adult
PubMed: 28460078
DOI: 10.1093/scan/nsx069