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Comparative Medicine Oct 2019Female urine-induced male mice ultrasonic vocalizations (FiUSV) are ultrasonic vocalizations produced by adult male mice after presentation of adult female urine,...
Female urine-induced male mice ultrasonic vocalizations (FiUSV) are ultrasonic vocalizations produced by adult male mice after presentation of adult female urine, whereas intruder-induced ultrasonic vocalizations (IiUSV) are produced by resident adult female mice when interacting with an intruder female mouse. These affiliative behaviors may be reduced when mice have decreased wellbeing or are in pain and distress. To determine whether FiUSV and IiUSV can be used as proxy indicators of animal wellbeing, we assessed FiUSV produced by male C57BL/6J mice in response to female urine and IiUSV produced by female C57BL/6J mice in response to a female intruder at baseline and 1 and 3 h after administration of a sublethal dose of LPS (6 or 12.5 mg/kg IP) or an equal volume of saline. Behavior was assessed by evaluating orbital tightness, posture, and piloerection immediately after USV collection. We hypothesized that LPS-injected mice would have a decreased inclination to mate or to interact with same-sex conspecifics and therefore would produce fewer USV. At baseline, 32 of 33 male mice produced FiUSV (149 ± 127 USV in 2 min), whereas all 36 female mice produced IiUSV (370 ± 156 USV in 2 min). Saline-injected mice showed no change from baseline at the 1- and 3-h time points, whereas LPS-injected mice demonstrated significantly fewer USV than baseline, producing no USV at both 1 and 3 h. According to orbital tightness, posture, and piloerection, LPS-injected mice showed signs of poor wellbeing at 3 h but not 1 h. These findings indicate that FiUSV and IiUSV can be used as proxy indicators of animal wellbeing associated with acute inflammation in mice and can be detected before the onset of clinical signs.
Topics: Animals; Female; Male; Mice; Mice, Inbred C57BL; Vocalization, Animal
PubMed: 31578163
DOI: 10.30802/AALAS-CM-18-000147 -
Frontiers in Neurology 2019The human skin is a highly specialized organ for receiving sensory information but also to preserve the body's homeostasis. These functions are mediated by cutaneous... (Review)
Review
The human skin is a highly specialized organ for receiving sensory information but also to preserve the body's homeostasis. These functions are mediated by cutaneous small nerve fibers which display a complex anatomical architecture and are commonly classified into cutaneous A-beta, A-delta and C-fibers based on their diameter, myelinization, and velocity of conduction of action potentials. Knowledge on structure and function of these nerve fibers is relevant as they are selectively targeted by various autonomic neuropathies such as diabetic neuropathy or Parkinson's disease. Functional integrity of autonomic skin nerve fibers can be assessed by quantitative analysis of cutaneous responses to local pharmacological induction of axon reflex responses which result in dilation of cutaneous vessels, sweating, or piloerection depending on the agent used to stimulate this neurogenic response. Sensory fibers can be assessed using quantitative sensory test. Complementing these functional assessments, immunohistochemical staining of superficial skin biopsies allow analysis of structural integrity of cutaneous nerve fibers, a technique which has gained attention due to its capacity of detecting pathogenic depositions of alpha-synuclein in patients with Parkinson's disease. Here, we reviewed the current literature on the anatomy and functional pathways of the cutaneous autonomic nervous system as well as diagnostic techniques to assess its functional and structural integrity.
PubMed: 31551921
DOI: 10.3389/fneur.2019.00970 -
PloS One 2019Recently the anti-viral effects of prophylactic treatment with the low-molecular-weight heparan sulfate mimetic PG545 in Ross River virus (RRV) infected mice were...
Recently the anti-viral effects of prophylactic treatment with the low-molecular-weight heparan sulfate mimetic PG545 in Ross River virus (RRV) infected mice were reported. We further investigated the related, transient pathophysiology of PG545 drug treatment in RRV-infected and mock-infected PG545-treated mice. PG545 treatment resulted in mild lethargy and piloerection, on days after the drug administration. Mice were treated with two or three doses of PG545 within a ten-day period and were subsequently culled at peak disease or at disease resolution. The treatment responses of the spleen and liver were assessed through histology, flow cytometry, gene arrays and serum biochemistry. Microscopy showed an expanded red pulp in the spleen following either two or three treatments with PG545. The red pulp expansion was further demonstrated by the proliferation of megakaryocytes and erythrocyte precursors within the spleen. In addition, flow cytometry and gene array analyses revealed a reduction of lymphocytes within the spleens of PG545-treated mice. Previously unreported, RRV-induced elevations of aspartate aminotransferase (AST) and alanine transaminase (ALT) enzymes and creatinine were also noted in the RRV-infected mice. However, PG545 only reduced AST and ALT levels but not the creatinine levels in infected mice during treatment. Mice treated with three doses of PG545 also showed hepatosplenomegaly and anaemia, which were reversed upon discontinuation of the treatment. In summary, this study demonstrates that dose and frequency related haemopoietic pathophysiology such as hepatosplenomegaly and anaemia, occurred in C57BL/6 mice treated with PG545. However, this effect was reversible once drug administration is terminated.
Topics: Alanine Transaminase; Alphavirus Infections; Animals; Aspartate Aminotransferases; Glucuronidase; Liver; Lymphocytes; Mice; Mice, Inbred C57BL; Ross River virus; Saponins; Spleen
PubMed: 31170255
DOI: 10.1371/journal.pone.0217998 -
PloS One 2019This study aimed to evaluate the potential adverse effects of the dermal administration of Dillenia indica Linnaeus (D. indica) fruit extract in healthy rodents; the...
This study aimed to evaluate the potential adverse effects of the dermal administration of Dillenia indica Linnaeus (D. indica) fruit extract in healthy rodents; the extract was standardized to betulinic acid. In the initial phase, the acute effects were evaluated on the skin application site of a single extract dose. A skin irritation test was performed in male Wistar rats (n = 8/group) receiving the extract (50-150 mg/mL) with betulinic acid (0.5-1.5%, respectively). A photosensitivity test was performed in male BALB/c mice (n = 6/group) receiving the extract (150 mg/mL). Afterwards, other BALB/c mice (n = 20, male:female, 1:1) were used to assess the systemic alterations caused by 14 daily repeated doses (150 mg/mL) by monitoring the effects on mortality, body morphology, behavior, nutrition status, neuromotor reactions, organ morphology and weight, and blood tests. At this time, 0.5 mg/mL clobetasol was used as the positive control. The skin irritation index suggested that negligible skin irritation had occurred, even when the extract was applied to the rat skin at 150 mg/mL. However, the extract acted as a photosensitizer on mouse skin, showing a photosensitizing activity close to that of 10 mg/mL 5-methoxypsoralen. Repeated doses caused no mouse mortality, aggressiveness, piloerection, diarrhea, convulsions, neuromotor alterations or nutrition status changes. The mouse organ weights did not change, and the mice did not have alterations in their blood compositions. Clobetasol caused a reduction in the mononuclear leukocyte numbers. In general, the data suggest that the extract was safe in healthy rodents but indicate that caution should be taken with the photosensitizing activity; in addition, this activity should be further explored as it may be useful for phototherapeutic drug development.
Topics: Administration, Cutaneous; Animals; Clobetasol; Dilleniaceae; Fruit; Humans; Leukocytes, Mononuclear; Mice; Pentacyclic Triterpenes; Photosensitizing Agents; Plant Extracts; Rats; Skin; Skin Irritancy Tests; Triterpenes; Betulinic Acid
PubMed: 31150479
DOI: 10.1371/journal.pone.0217718 -
The Journal of Neuroscience : the... May 2019Anxiety disorders are characterized by excessive attention to threat. Several brain areas, including the orbitofrontal cortex (OFC), have been associated with threat...
Anxiety disorders are characterized by excessive attention to threat. Several brain areas, including the orbitofrontal cortex (OFC), have been associated with threat processing, with more recent work implicating specialized roles for the medial and lateral subregions of the OFC in mediating specific symptoms of anxiety disorders. Virtually no causal work, however, has evaluated the role of these OFC subregions in regulating behavioral responses under threat. To address this gap, we compared male rhesus monkeys () with bilateral excitotoxic lesions restricted to either the lateral OFC (lOFC), targeting Walker's areas 11 and 13, or the medial OFC (mOFC), targeting Walker's area 14, to a group of unoperated controls on behavioral responses to the presentation of a fake rubber snake, fake spider, and neutral stimuli. Both lesion groups showed heightened defensive and reduced approach responses, accompanied by longer latencies to retrieve a food reward, in the presence of the threatening stimuli. Compared to unoperated controls, the mOFC lesion group also showed longer latencies to reach for rewards and a greater proportion of defensive responses (e.g., piloerection) in the presence of neutral stimuli. Thus, monkeys with mOFC lesions displayed a greater tendency to express defensive responses even in the absence of threat. Overall, our data reveal that both the mOFC and lOFC contribute to the attenuation of defensive responses. Notably, these findings, obtained following selective, excitotoxic lesions of the OFC, are diametrically opposed to the effects of aspiration lesions of OFC observed in macaques. Engaging in adaptive defensive responses under threat promotes biological fitness. The orbitofrontal cortex (OFC) has been implicated in regulating defensive responses to threat, with distinct subregions likely playing different roles. Here we tested the effects of excitotoxic damage restricted to either the lateral or medial subdivisions of the OFC in rhesus macaques. We found significantly heightened defense and reduced approach responses to threatening stimuli in both lesion groups. While lateral OFC lesions led to an increase in defense responses to the threatening stimuli, medial OFC lesions produced increases in defense responses to both threatening and neutral stimuli. Our findings provide insights into the neural regulation of defensive responses to threat and inform the etiology and treatment of anxiety disorders in humans.
Topics: Animals; Behavior, Animal; Female; Macaca mulatta; Male; Prefrontal Cortex
PubMed: 30910790
DOI: 10.1523/JNEUROSCI.2812-18.2019 -
Biomedicine & Pharmacotherapy =... Apr 2019An extracellular polysaccharide (EPS1-1) of Rhizopus nigricans was found to enhance immunity and reduce colon cancer cell proliferation. Here, the effect of EPS1-1 on a...
An extracellular polysaccharide (EPS1-1) of Rhizopus nigricans was found to enhance immunity and reduce colon cancer cell proliferation. Here, the effect of EPS1-1 on a mouse model of colitis-associated cancer (CAC) induced by azoxymethane (AOM)/dextran sodium sulfate (DSS) was investigated. Pathological symptoms, including weight loss, piloerection, hematochezia and insensitivity caused by AOM/DSS, were relieved by EPS1-1. Anatomical results showed a 100% tumor incidence, a series of neoplasms, disordered cell structure and hyperplastic glands in the model group, while the abnormal behaviors were relieved and the tumors decreased in the EPS1-1 group. Compared with the model group, the EPS1-1 group showed decreased oncogenic protein (COX-2, β-catenin, CyclinD1 and C-Myc) expression. TUNEL staining showed that EPS1-1 increased the apoptosis of colon cancer cells in mice. Furthermore, the expression of proliferative proteins (Ki-67 and PCNA) and an antiapoptotic gene transcript (Bcl-2) were significantly down regulated by EPS1-1, while apoptotic gene transcripts (p53 and Bax) were enhanced. In addition, EPS1-1 notably decreased the number of cells positive for CD68, F4/80 and NF-κB and reduced the concentrations of inflammatory factors (TNF-α and IL-6) in serum compared with those in the model group. Taken together, these results suggest that EPS1-1 may be a therapeutic option for the prevention and treatment of CAC.
Topics: Animals; Cell Proliferation; Colitis; Colon; Colorectal Neoplasms; Fungal Polysaccharides; Male; Mice; Mice, Inbred BALB C; Rhizopus; Treatment Outcome
PubMed: 30784912
DOI: 10.1016/j.biopha.2019.01.054 -
Seizure Jan 2019To comprehensively analyze ictal piloerection (IP) in a large number of subjects.
PURPOSE
To comprehensively analyze ictal piloerection (IP) in a large number of subjects.
METHODS
We performed a systematic review on case report studies of patients diagnosed with IP (1929-2017) with additional cases included from the Department of Neurology of University of Pécs, the National Institute of Clinical Neurosciences, and Odense University Hospital. Each included case was characterized regarding patient history, IP seizure characteristics, diagnostic work-up, and therapy. Comparative analyses were also carried out based on sex and pathology.
RESULTS
Altogether, 109 cases were included. We observed a strong male predominance (p < 0.001). The mean age at onset of epilepsy was 39.5 ± 20.7 years (median: 38, IQR:24-57). The seizure onset zone was temporal (p < 0.001), and was lateralized to the ipsilateral hemisphere in unilateral localization (p = 0.001). The seizure was accompanied by cold shiver in 53%, and by other autonomic symptoms in 47% of cases. In 53% of patients, IP never progressed into complex partial or generalized tonic-clonic seizure; 16% of the patients reported occasional, and 31% regular generalization. Seizure frequency was higher among females (median:25/day, IQR:3-60) than among males (median:3/day, IQR:1-11) (p = 0.017). The two most common underlying pathologies were limbic encephalitis (23%) and astrocytoma (23%, among them 64% WHO III-IV astrocytoma).
CONCLUSION
IP was particularly associated with autoimmune encephalitis and high-grade glioma, suggesting IP's particular clinical importance in directing diagnostic work-up.
Topics: Adult; Autonomic Nervous System; Brain Neoplasms; Epilepsy, Temporal Lobe; Female; Glioma; Humans; Limbic Encephalitis; Male; Middle Aged; Piloerection
PubMed: 30497014
DOI: 10.1016/j.seizure.2018.11.009 -
Journal of Ethnopharmacology Dec 2018Terminalia argentea Mart. (Combretaceae), known mainly as "capitão", is a native tree, not endemic, that occurs in the Amazon, Caatinga, Cerrado and Atlantic Forest in...
ETHNOPHARMACOLOGICAL RELEVANCE
Terminalia argentea Mart. (Combretaceae), known mainly as "capitão", is a native tree, not endemic, that occurs in the Amazon, Caatinga, Cerrado and Atlantic Forest in Brazil. Leaf infusion is popularly mentioned by riverine communities that inhabit the microregion of Northern Araguaia (Mato Grosso, Brazil) for the treatment of gastric ulcer, bronchitis and haemorrhage. Considering the wide medicinal use, lack of studies that evaluate the safety of use and the scarcity of phytochemical studies of T. argentea leaves, this work was carried out with the objective of evaluating the toxicity of the hydroethanolic extract of the leaves of T. argentea Mart. (HETa) in experimental models in vivo and in vitro, as well as to advance the phytochemical analysis of HETa.
MATERIALS AND METHODS
HETa was prepared by macerating the leaf powder in hydroethanolic solution. Phytochemical characterisation was carried out by thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC) and mass spectrometry through direct flow infusion coupled with electrospray ionization and ion-trap analyzer (DFI-ESI-IT-MS analyses) The contents of phenols, flavonoids and phytosterols were analysed by colorimetric methods. Cytotoxicity was assessed by the Alamar blue assay on Chinese hamster ovary epithelial cells (CHO-K1) and human gastric adenocarcinoma cells (AGS). In vitro genotoxicity of HETa (10, 30 or 100 μg/mL) was assessed by micronucleus (MN) and comet tests using CHO-K1 cells. The acute toxicity assessment was performed by oral administration of HETa in single dose Swiss mice (males and females) up to 2000 mg/kg and sub-chronic toxicity by daily oral administration of HETa (50, 200 and 800 mg/kg) in Wistar rats for 30 days. The parameters related to the clinical and toxicological observations were determined every 6 days and at the end of the treatment the blood was collected for biochemical and haematological analysis, and some organs were removed for macroscopic and histopathological analysis.
RESULTS
Preliminary phytochemistry and TLC analysis of HETa revealed the presence of phenolic compounds (18.8%), flavonoids (10.8%), saponins, tannins and phytosterols (19%). The HPLC data revealed the presence of gallic acid, rutin, ellagic acid, catechin, quercetin and kaempferol. In the analysis by DFI-ESI-IT-MS, the presence of gallic acid, rutin, ellagic acid and quercetin was confirmed and identified caffeic acid, quinic acid, galloylmucic acid, quercetin xyloside, quercetin rhamnoside, quercetin glucoside, caffeoyl ellagic acid, quercetin galloyl xyloside, terminalin, quercetin galloyl glucose, corilagin, quercetin digalloyl xyloside, quercetin digalloyl glucoside, punicalin and punicalagin. HETa showed no cytotoxic effect on CHO-K1 and AGS cells. In the MN assay, HETa increased the number of MNs and nuclear buds (NBUDs) in binucleate cells at the three concentrations tested and the nucleoplasmic bridges (NPBs) number at 30 μg/mL. In the comet test, HETa (10 and 100 μg/mL) alone showed a genotoxic effect on CHO-K1 cells. In pre-treatment, HETa at all concentrations tested prevented DNA damage induced by HO. In co-treatment with HO, HETa showed genotoxic effects at the three concentrations, and post-treatment DNA damage in exposed CHO-K1 cells to HO was repaired in 22.5% with 10 μg/mL HETa. In the acute toxicity test, the HETa did not cause death in the mice, being verified only by piloerection and reversible in 2 h in males and in 4 days in females. No macroscopic changes were observed in the analysed organs. In the sub-chronic toxicity test, the HETa did not cause death in the rats after 30 days and the few changes were: absolute (10/mm) and relative (%) values of basophils increased by 477.8% and 423% (p < 0.001), respectively, with 50 mg/kg; reduction in feed intake (23.6%, p < 0.01) only on day 18; total cholesterol concentration (13.1%, p < 0.05) and relative heart weight (13.2% %, p < 0.05) at a dose of 800 mg/kg. These effects were not dose-dependent nor followed by clinical signs and symptoms of intoxication, nor of macroscopic and histopathological changes in the organs of animals treated with HETa.
CONCLUSIONS
The results demonstrated that HETa had no cytotoxic in vitro effects for CHO-K1 and AGS cells. In in vitro genotoxicity assays, the HETa induced different responses, according to concentration and experimental condition. In the MN test the HETa presented genotoxic potential by increasing the number of MNs, NBUDs and NPBs. In the comet assay, HETa was genotoxic by itself and in the co-treatment protocol with HO. In pre-treatment or post-treatment protocols with HO, HETa presented an antigenotoxic effect by preventing or repairing, respectively, the genotoxicity induced by HO. In the in vivo models, HETa was shown to be relatively safe after acute administration in mice [no-observed-adverse effect level (NOAEL) of 2000 mg/kg] and sub-chronic in rats (NOAEL of 800 mg/kg), confirming the riverine information that it is non-toxic in the dosage used. Phytochemical analysis of HETa revealed the presence of phenolic compounds, flavonoids, saponins, tannins and phytosterols. Among the flavonoids and tannins, we highlight gallic acid, rutin, ellagic acid, quercetin, caffeic acid, quinic acid, corilagin, punicalin and punicalagin. Thus, it can be stated that HETa has a good safety margin for therapeutic use.
Topics: Animals; CHO Cells; Cell Line, Tumor; Cell Survival; Cricetulus; Ethanol; Female; Humans; Male; Mice; Mutagenicity Tests; Phytochemicals; Plant Extracts; Plant Leaves; Rats, Wistar; Solvents; Terminalia
PubMed: 30142424
DOI: 10.1016/j.jep.2018.08.025 -
PeerJ 2018Autonomic nervous systems in the human body are named for their operation outside of conscious control. One rare exception is voluntarily generated piloerection...
Autonomic nervous systems in the human body are named for their operation outside of conscious control. One rare exception is voluntarily generated piloerection (VGP)-the conscious ability to induce goosebumps-whose physiological study, to our knowledge, is confined to three single-individual case studies. Very little is known about the physiological nature and emotional correlates of this ability. The current manuscript assesses physiological, emotional, and personality phenomena associated with VGP in a sample of thirty-two individuals. Physiological descriptions obtained from the sample are consistent with previous reports, including stereotypical patterns of sensation and action. Most participants also reported that their VGP accompanies psychological states associated with affective states (e.g., awe) and experience (e.g., listening to music), and higher than typical openness to new experiences. These preliminary findings suggest that this rare and unusual physiological ability interacts with emotional and personality factors, and thus merits further study.
PubMed: 30083447
DOI: 10.7717/peerj.5292 -
Toxicological Research Jul 2018Currently, injuries to customers due to health functional foods are annually increasing. To evaluate the antigenicity of Korean red ginseng mixture (KRGM), we tested for...
Currently, injuries to customers due to health functional foods are annually increasing. To evaluate the antigenicity of Korean red ginseng mixture (KRGM), we tested for systemic anaphylactic shock and passive cutaneous anaphylaxis in guinea pigs. Based on a comparison of measured body weights, there were no changes in body weight for the KRGM treatment group compared with the control group. In the ovalbumin treated group, however, there was a statistically significant decrease in body weight. For the active systemic anaphylaxis test, after the induction, there were no symptoms that suggested anaphylactic shock in the control and KRGM treatment group. In the ovalbumin treated group, there were symptoms that suggested severe anaphylaxis, and those symptoms included restlessness, piloerection, tremor, rubbing or licking the nose, sneezing, coughing, hyperpnea, dyspnea, staggering gait, jumping, gasping and writhing, convulsion, side position and Cheyne-stokes respiration. All animals died within thirty minutes in the ovalbumin treated group. For the passive cutaneous anaphylaxis test in guinea pigs sensitized to KRGM, each anti-serum was diluted in a stepwise manner. This was followed by an intravenous injection of a mixture of KRGM and Evans blue. The results of the test showed that all the responses were negative in the control and the low-dose and high-dose administration groups. However, in the ovalbumin treated group, all the responses were positive. Based on the above results, there were no anaphylactic responses for up to 12 times the amount of human intake of KRGM in Hartley Guinea-pigs. The results suggest that KRGM is safe as measured by the systemic and local antigenicity in guinea pigs.
PubMed: 30057692
DOI: 10.5487/TR.2018.34.3.183