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Journal of Virological Methods Nov 2021This study examined the anti-HSV-1 activity of EPS extracts isolated from mangrove fungus Paecilomyces Lilacinuson after intraperitoneal administration in mice. Mice...
This study examined the anti-HSV-1 activity of EPS extracts isolated from mangrove fungus Paecilomyces Lilacinuson after intraperitoneal administration in mice. Mice were experimentally infected with HSV-1 intracranially and treated intraperitoneally with three different doses of EPS extract (6 g/Kg, 8 g/Kg, and 10 g/Kg) for 7 days. One group of 15 mice was infected with HSV-1 but did not receive any treatment, while another group of 15 mice was mock-infected to remain a control group. Animals were observed twice a day for 14 days after virus infection, searching for clinical signs of weight loss, piloerection, isolation, or retardation movement. Compared with the mock-infected group, mortality was significantly increased (p < 0.05) in the virus-infected group and the groups that received 6 g/Kg and 8 g/Kg EPS extract. Interestingly, no significant differences in mortality were found between the 10 g/Kg EPS extract and the mock-infected group. Mortality in the 10 g/Kg EPS extract group was substantially improved compared with virus-infected(p < 0.05). Additionally, EPS extracts inhibited HSV-1 replication in the mice brain in a dose-dependent manner. Furthermore, the extracts decreased NF-κB protein and mRNA expression and the production of TNF-α in HSV-1-infected mice brain tissue. These effects were also dose-dependent. Our findings suggest that the EPS extract may be a potential candidate for developing an antiviral drug against HSV-1.
Topics: Animals; Antiviral Agents; Herpesvirus 1, Human; Mice; NF-kappa B; Paecilomyces; Polysaccharides; Tumor Necrosis Factor-alpha
PubMed: 34329630
DOI: 10.1016/j.jviromet.2021.114246 -
Cognition & Emotion Sep 2022Emotional experiences typically labelled "being moved" or "feeling touched" may belong to one universal emotion. This emotion, which has been labelled "kama muta", is...
Emotional experiences typically labelled "being moved" or "feeling touched" may belong to one universal emotion. This emotion, which has been labelled "kama muta", is hypothesised to have a positive valence, be elicited by sudden intensifications of social closeness, and be accompanied by warmth, goosebumps and tears. Initial evidence on correlations among the kama muta components has been collected with self-reports after or during the emotion. Continuous measures during the emotion seem particularly informative, but previous work allows only restricted inferences on intra-individual processes because time series were cross-correlated across samples. In the current studies, we instead use a within-subject design to replicate and extend prior work. We compute intra-individual cross-correlations between continuous self-reports on feeling moved and (1) positive and negative affect; (2) goosebumps and subjective warmth and (3) appraisals of closeness and morality. Results confirm the predictions of kama muta theory that feeling moved by intensified communal sharing cross-correlates with appraised closeness, positive affect, warmth and (less so) goosebumps, but not with negative affect. Contrary to predictions, appraised morality cross-correlated with feeling moved as much as appraised closeness did. We conclude that strong inferences on emotional processes are possible using continuous measures, replace earlier findings, and are largely in line with theorising.
Topics: Humans; Time Factors; Emotions; Piloerection; Sensation; Morals
PubMed: 35731041
DOI: 10.1080/02699931.2022.2089871 -
Seizure May 2022Ictal piloerection (IP) is a rare manifestation of focal epilepsy. Autoimmune limbic encephalitis (LE) and malignant brain tumours are the most frequent recognized... (Review)
Review
BACKGROUND
Ictal piloerection (IP) is a rare manifestation of focal epilepsy. Autoimmune limbic encephalitis (LE) and malignant brain tumours are the most frequent recognized aetiologies.
METHODS
We selected all patients diagnosed with LE in our Institute from 2004 to 2020 and manifesting with IP. We performed a literature review on LE patients presenting IP.
RESULTS
Of 15 patients diagnosed with LE (13.3%), two manifested IP as prominent ictal feature. One of them also had stiff-limb syndrome. Video-EEG documented ictal discharges from the right temporal regions with concomitant sympathetic skin response (SSR) recording. Antibody testing showed elevated serum and CSF titres of GAD65 antibodies (Ab), in both cases. Despite a combination of several anti-seizure medications and first- and second-line immunotherapy, they showed a poor clinical outcome after 2 and 9 years of follow-up, respectively. The literature review yielded 13 papers reporting 26 LE cases with IP. LGI1 Ab were the most frequently associated (73.1%) followed by VGKC-complex (7.7%), GAD65 (7.7%), NMDAr (3.8%), Ma2 (3.8%) and Hu (3.8%) Ab. Cases with LGI1 Ab showed a good response to immunotherapy.
DISCUSSION AND CONCLUSION
The prevalence of IP in our LE cohort was of 13.3%, higher than expected. According to the literature review, most cases were associated with LGI1 Ab and showed a good response to immunotherapy. With the contribution of our cases, GAD65 emerged as the second most frequently detected Ab, showing a poor outcome. Our findings widen the spectrum of IP-associated Ab, with the respective prognostic implications.
Topics: Autoantibodies; Autoimmune Diseases; Electroencephalography; Humans; Limbic Encephalitis
PubMed: 35427850
DOI: 10.1016/j.seizure.2022.03.025 -
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 -
Journal of Ethnopharmacology Jan 2018The traditional uses of Corydalis dubia, Ajania nubigena and Pleurospermum amabile in the Bhutanese traditional medicine for treating disorders related to inflammatory...
ETHNOPHARMACOLOGICAL RELEVANCE
The traditional uses of Corydalis dubia, Ajania nubigena and Pleurospermum amabile in the Bhutanese traditional medicine for treating disorders related to inflammatory conditions and the in vitro anti-inflammatory activity of their crude extracts inspired the isolation and the investigation of anticolitic properties of four pure compounds.
MATERIALS AND METHODS
Three medicinal plants were collected from Himalayan Mountains of Bhutan. Capnoidine and scoulerine were isolated from C. dubia, linalool oxide acetate from A. nubigena and isomyristicin from P. amabile using natural product isolation protocols. Four compounds were investigated for their anti-inflammatory activities against IBD-colitis using chemically induced (TNBS) mice model of colitis. Capnoidine conferred the best preliminary protection against TNBS-induced colitis in mice and we have conducted in-depth pharmacological investigation of this compound including clinical symptoms, pathological signs, cytokine profiles, histological structure and inflammasomes using relevant bioassay protocols.
RESULTS
Capnoidine-treated mice had significantly: a) improved clinical symptoms (body weight loss, mobility, piloerection and faecal consistency); b) reduced colon pathology (adhesion, oedema, ulceration, and colon length); c) altered inflammatory cytokines profiles within the colons; d) reduced levels of p-IκB-α (Ser32) and p-NF-κB p65 (Ser536) and e) reduced histological inflammation in the colon when compared with mice administered TNBS only.
CONCLUSION
Capnoidine presents as a potential new anti-inflammatory drug lead candidate for diseases where current standard-of-care often fails and is associated with major side effects. It also validates the traditional uses of C. dubia against inflammatory conditions and underlines the value of pursuing bioactive compounds derived from traditionally used ethnobotanical medicines.
Topics: Animals; Anti-Inflammatory Agents; Bhutan; Colitis; Colon; Corydalis; Cytokines; Male; Medicine, Traditional; Mice, Inbred C57BL; Plant Extracts; Plants, Medicinal; Trinitrobenzenesulfonic Acid
PubMed: 28942135
DOI: 10.1016/j.jep.2017.09.024 -
Toxicology Reports 2020Cannabinoids are extracted from L. and are used for a variety of medicinal purposes. Recently, there has been a focus on the cannabinoid Cannabidiol (CBD) and its...
Cannabinoids are extracted from L. and are used for a variety of medicinal purposes. Recently, there has been a focus on the cannabinoid Cannabidiol (CBD) and its potential benefits. This study investigated the safety of a proprietary extract of consisting of 9% hemp extract (of which 6.27% is CBD) and 91% olive oil. The mutagenic potential of the hemp extract was evaluated with the AMES assay inclusive of a hepatic drug metabolizing mix (S9) rich in CYP enzymes. The test article did not elicit evidence of bacterial mutagenicity. GLP compliant 14-day and a 90-day toxicity study were conducted. Olive oil was used as a control. The 90-day study had a 28-day recovery period. Treatments for the 14-day non-recovery range-finding study were 0, 1000, 2000 and 4000 mg test article/kg body weight (bw)/day for 14 days. There was a non-statistically significant ( > 0.05) decrease in body weights for the male and female rats receiving the test article. Hypoactivity, hyperactivity, reduced food consumption and piloerection were observed in the rats receiving 4000 mg test article/kg bw. Histopathology showed an increase in the size of liver cells (hypertrophy) around the central vein (centrilobular) in Groups 3 (3/10) and 4 (5/10) that correlated with increased liver weights. In the 90-day study, 8 groups of rats were dosed with 0, 200, 400 and 800 mg test article/kg bw/day. Groups 5 to 8 had a 28-day recovery. There were no test article-linked changes in clinical observations, physical examinations, Functional Observation Battery, ophthalmology, Motor Activity Assessment, hematology, clinical chemistries and macropathology (all groups). With the exception of the liver and adrenal gland, no test article-linked pathology was observed. For all rats receiving the test article, histopathology showed hypertrophy of liver cells around the central vein. The increase of liver weight is most likely caused by hypertrophy due to up-regulation of the hepatic drug metabolizing enzymes. The hepatocellular hypertrophy was completely reversed in 28 days and was not considered to be an adverse effect. Vacuolization of the adrenal zona fasciculata was observed in the control and 800 mg test article/kg bw groups. The vacuolization of the zona fasciculata was of the same incidence and severity in treatment and control male rats and correlated with an increased in the weights of the adrenal glands. In addition, a statistically significant increase (p<0.05) in adrenal-to-body weight ratios was observed for females receiving 800 mg test article/kg bw. This increase in adrenal-to-body weight ratio did not correlate with any of the pathology findings. The NOAEL for the test article is 800 mg/kg bw/day for female and 400 mg/kg bw/day for male Sprague Dawley rats.
PubMed: 32123668
DOI: 10.1016/j.toxrep.2020.02.014 -
Frontiers in Zoology Mar 2022Sexual selection has driven sexual dimorphism in agonistic behaviour in many species. Agonistic behaviour is fundamentally altered by domestication and captivity, but it...
BACKGROUND
Sexual selection has driven sexual dimorphism in agonistic behaviour in many species. Agonistic behaviour is fundamentally altered by domestication and captivity, but it is unclear whether ancestral sex differences remain. We aimed to evaluate the effect of sex on agonistic behaviour, fighting ability and contest costs. We studied this in domestic pigs (Sus scrofa) where aggression compromises welfare, and sexual dimorphism in aggression has been inconclusively demonstrated. Behaviour and physiology of 827 male and female juvenile pigs were studied during resident-intruder tests and dyadic contests at various ages, while accounting for the relative body weight difference between the opponents.
RESULTS
Males won in 79% of contests against females, even when at a large weight disadvantage. The effect of sex increased with age, with males having a 138 times higher likelihood of winning than females when 13 weeks old. In dyadic contests, males invested more time in non-damaging agonistic display behaviour and took longer before escalating into damaging aggression. Males showed ritualized display that included foaming from the mouth and piloerection of the neck hair, which was nearly always absent in females. Contest costs in terms of contest duration, blood lactate and skin lesions where higher for males, especially when fighting another male.
CONCLUSIONS
Profound sex differences were present for agonistic behaviour, fighting ability and contest costs, and became more pronounced as animals got older. Males invested more in ritualized display before escalating into costly fights, whereas females attacked sooner but also terminated contests more rapidly and with fewer costs. The sexual dimorphism in agonistic behaviour in juvenile domestic pigs is in line with the evolutionary relevance for females' maternal defence and males' competition for females.
PubMed: 35279172
DOI: 10.1186/s12983-022-00458-9 -
Royal Society Open Science Oct 2021Consolation has been observed in several species, including marmoset monkeys, but it is often unclear to what extent they are empathy-based. Marmosets perform well in at...
Consolation has been observed in several species, including marmoset monkeys, but it is often unclear to what extent they are empathy-based. Marmosets perform well in at least two of three components of empathy-based consolation, namely understanding others and prosociality, but it is unknown to what extent they show matching with others. We, therefore, tested whether non-aroused individuals would become aroused themselves when encountering an aroused group member (indicated by piloerection of the tail). We found a robust contagion effect: group members were more likely to show piloerection themselves after having encountered an aroused versus relaxed conspecific. Moreover, group members offered consolation behaviours (affiliative approaches) towards the aroused fellow group members rather than the latter requesting it. Importantly, this pattern was shown by both aroused and non-aroused individuals, which suggests that they did not do this to reduce their own arousal but rather to console the individual in distress. We conclude that marmosets have all three components of empathy-based consolation. These results are in line with observations in another cooperative breeder, the prairie vole.
PubMed: 34729211
DOI: 10.1098/rsos.211255 -
Journal of Neurology Mar 2016Autonomic dysfunction has frequently been reported in autoimmune encephalitis associated with seizures and there is growing evidence that epilepsy patients may display...
Autonomic dysfunction has frequently been reported in autoimmune encephalitis associated with seizures and there is growing evidence that epilepsy patients may display neuronal autoantibodies (NAAb). The aim of this study was to investigate the frequency of NAAb in epilepsy patients with peri-ictal autonomic findings. Fifty-eight patients (37 women/21 men; average age of 34.2 ± 9.9 years and epilepsy duration of 19.1 ± 9.6 years) who had at least one video-EEG recorded focal or secondary generalized seizure with clear-cut documented peri-ictal autonomic findings, or consistently reported seizures with autonomic semiology, were included. NAAb were tested by RIA or cell based assays. NAAb were present in 17 of 58 (29.3%) patients. Among seropositive patients, antibodies were directed against N-methyl-D-aspartate receptor (NMDAR) in 5 (29%), contactin-associated protein-like 2 (CASPR2) in 5 (29%), uncharacterized voltage gated potassium channel (VGKC)-complex antigens in 3 (18%), glutamic acid decarboxylase (GAD) in 2 (12%), glycine receptor (GLYR) in one (6%) and type A gamma aminobutyric acid receptor (GABAAR) in one patient (6%). Peri-ictal gastrointestinal manifestations, piloerection, ictal fever, urinary urge, and cough occurred more commonly in the seropositive group. The prevalences of psychotic attacks and status epilepticus were significantly increased in the seropositive group. Seropositivity prevalence in our patient group with peri-ictal autonomic findings is higher than other previously reported epilepsy cohorts. In our study, ictal fever-VGKC-complex antibody and pilomotor seizure-GABAAR antibody associations were documented for the first time. Chronic epilepsy patients with peri-ictal autonomic semiology, history of status epilepticus and psychotic disorder may benefit from autoantibody screening.
Topics: Adolescent; Adult; Autoantibodies; Autonomic Nervous System Diseases; Chi-Square Distribution; Electroencephalography; Epilepsy; Female; Follow-Up Studies; Glutamate Decarboxylase; Humans; Male; Membrane Proteins; Middle Aged; Nerve Tissue Proteins; Potassium Channels, Voltage-Gated; Receptors, Glycine; Receptors, N-Methyl-D-Aspartate; Young Adult
PubMed: 26725084
DOI: 10.1007/s00415-015-8002-2 -
European Journal of Pharmaceutical... Mar 2018Vaccines typically come with adjuvants that trigger the innate immune system in order to prepare best possible inflammatory conditions as to allow the adaptive immune...
Vaccines typically come with adjuvants that trigger the innate immune system in order to prepare best possible inflammatory conditions as to allow the adaptive immune system to become activated, generally for the induction of antibodies. The oldest approved and most abundant immunological adjuvants are salts of aluminium, which are also frequently used in animal models of immunisation and allergy desensitization. In rodents, the intraperitoneal administration of aluminium adjuvants is commonly performed and considered safe. In the current investigation, we show that intraperitoneal administration of aluminium adjuvants is associated with a dose-dependent hypothermic reaction within 10 min of the injection. The body temperature of mice dropped as much as 4 °C, and the clinical symptoms included apathy, hunched posture, and piloerection. The temperature normalised and other clinical manifestations disappeared within 60-80 min of the intraperitoneal aluminium injection, which caused strong infiltration of neutrophil and eosinophil granulocytes into the peritoneal cavity, a clinical manifestations typically associated with inflammasome activation. However, the observed reactions to aluminium adjuvants were independent of NALP3, caspase-1, and interleukin-1β, but dependent on histamine. Hence, aluminium adjuvants may have potential local and systemic side effects, which warrants further investigations into the nature of these side effects, but also into the possible implications on health in man.
Topics: Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Aluminum; Animals; Antibodies; Female; Immunization; Injections, Intraperitoneal; Interleukin-1beta; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Vaccination; Vaccines
PubMed: 29410031
DOI: 10.1016/j.ejps.2018.01.042