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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 -
Regulatory Toxicology and Pharmacology... Apr 2019Midkine antisense oligonucleotide (MK-ASODN) nanoliposomes have previously been shown to have inhibitory activity against hepatocellular carcinoma growth. Herein we...
Midkine antisense oligonucleotide (MK-ASODN) nanoliposomes have previously been shown to have inhibitory activity against hepatocellular carcinoma growth. Herein we report the 4-week sub-chronic toxicity of MK-ASODN nanoliposomes in SD rats. The adverse effects included loss of body weight gain and food consumption, peri-rhinal bleeding, piloerection, peri-anal filth, and kidney, liver, spleen, thymus, lung, and injection site lesions at high doses. Macroscopic changes were observed in the kidneys of the high-dose group, accompanied by a variation in urine protein and white blood cells, blood urea nitrogen, and serum creatinine. The increased spleen and liver coefficient, and the variation in circulating white blood cells, lymphocytes, and eosinophils in the high-dose group demonstrated that inflammation was caused by MK-ASODN nanoliposomes and was consistent with the macroscopic changes in the spleen and liver. The main necropsy findings of the animals that died were macroscopic changes in the lung. No severe toxic effects or mortalities occurred in the low- and medium-dose groups. However, a No Adverse Effect Level (NOAEL) was not identified since there were changes in organs deemed to be adverse at all dose levels. Thus, the maximum tolerated dose of MK-ASODN nanoliposomes for rats was considered to be 6 mg/kg/day.
Topics: Animals; Dose-Response Relationship, Drug; Female; Injections, Intravenous; Liposomes; Liver; Male; Midkine; Nanoparticles; Oligonucleotides, Antisense; Rats; Rats, Sprague-Dawley; Spleen
PubMed: 30682377
DOI: 10.1016/j.yrtph.2019.01.030 -
Cognition & Emotion Nov 2019People can be moved and overwhelmed, a phenomenon typically accompanied by goose-bumps and tears. We argue that these feelings of being moved are not limited to...
People can be moved and overwhelmed, a phenomenon typically accompanied by goose-bumps and tears. We argue that these feelings of being moved are not limited to situations that are appraised as pro-social but elicited when someone surpasses an internal standard. In line with these predictions, people were moved by relationships and success (Study 1), by reunion, separation, success and failure (Study 2) and by social, environmental and sports achievements (Study 3). In all three studies, the elicitation of these feelings was partially mediated by appraisals of surpassing social or achievement standards. In line with this, ratings of meaningfulness were closely associated with feelings of being moved and moving stimuli elicited behavioural intentions such as spending time with family and friends, helping others and/or achieving something in life. Thus, moving situations may remind us about what we perceive as meaningful and thereby help us to act accordingly.
Topics: Achievement; Adolescent; Adult; Aged; Cooperative Behavior; Emotions; Female; Friends; Germany; Humans; Intention; Interpersonal Relations; Male; Middle Aged; Piloerection; Social Values; Sports; Tears; Young Adult
PubMed: 30676264
DOI: 10.1080/02699931.2019.1567463 -
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 -
The Spanish Journal of Psychology Oct 2018The Spanish term grima refers to the aversive emotional experience typically evoked when one hears, for example, a scratch upon a chalkboard. Whereas Spanish speakers...
The Spanish term grima refers to the aversive emotional experience typically evoked when one hears, for example, a scratch upon a chalkboard. Whereas Spanish speakers can distinguish between the concepts of grima and disgust, English and German speakers lack a specific word for this experience and typically label grima as disgust. In the present research, we tested the degree of differentiation between the two aversive experiences in Spanish speakers. Study 1 addressed whether Spanish speakers apply spontaneously the term grima rather than disgust to grima-eliciting experiences. Study 2 systematically addressed the constitutive features of both grima and disgust by mapping their internal structures. Results showed that the noise of a chulk on a blackboard and scraping fingernails on a blackboard, along with the physical manifestation of goose bumps, were the most typical features of the category. Whereas both grima and disgust were characterized as unpleasant sensations, t(193) = 1.21, ns, they differed with respect to their physiological signatures (e.g., producing shivers was characteristic of grima, as compared to disgust, t(194) = 12.02, p = .001, d = 1.72) and elicitors (e.g., a fractured bone was a characteristic elicitor of grima; t(193) = 5.78, p = .001, d = .83, whereas pederasts and pedophiles were the most characteristic elicitor of disgust, t(193) = 8.46, p = .001, d = 1.21). Thus, both grima and disgust are conceptually different experiences, whose shared features hold different degrees of typicality. The present research suggests that grima and disgust are two distinct emotion concepts.
Topics: Adult; Auditory Perception; Disgust; Emotions; Female; Humans; Language; Male; Piloerection; Social Perception; Young Adult
PubMed: 30355380
DOI: 10.1017/sjp.2018.40 -
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 -
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