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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 -
Journal of the American Academy of... Jun 2024
PubMed: 38871084
DOI: 10.1016/j.jaad.2024.05.082 -
Hepatic Medicine : Evidence and Research 2022Eighty percent of Ethiopians use traditional medicine, one of which is the leaf of .
BACKGROUND
Eighty percent of Ethiopians use traditional medicine, one of which is the leaf of .
OBJECTIVE
To investigate subacute toxicity of aqueous extracts of leaves on the liver and kidney and biochemical parameters in Swiss albino mice.
METHODS
LD was assessed with nine experimental groups and one control group of adult female Swiss albino mice (five in each group). In the subacute study, 40 mice of both sexes were randomly divided into four groups of ten mice (both sexes) per group. Group I served as controls and received distilled water and feed only. Groups II-IV were used as treatment groups. They received calculated doses of aqueous leaf extracts orally at doses of 500 mg/kg, 1000 mg/kg, and 2000 mg/kg body weight, respectively.
RESULTS
Since 80% of deaths occurred at the 10,000 mg/kg body-weight dose in this experiment, LD was considered to be <10,000 mg/kg. In the subacute test, general signs of toxicity like hypoactivity, piloerection, lethargy, and a single episode of convulsion were observed at the 2000 mg/kg dose. Beginning from the third week of administration, both male and female mice receiving 500 mg/kg and 2000 mg/kg and all treatment groups in the fourth week showed significant (<0.05) weight loss compared to controls. Biochemical parameters were found to increase in all groups treated with ethanolic leaf extracts. Several histopathological changes like congestion, hemorrhage, severe necrosis, and infiltration of inflammatory cells in both liver and kidney in the -treated rats were observed at all doses.
CONCLUSION
In the present study, the ethanolic leaf extracts of produced dose-dependent weight loss and histopathological and biochemical changes in Swiss albino mice.
PubMed: 36171754
DOI: 10.2147/HMER.S370927 -
Biology Letters Jan 2023We identify for wild, free-living short-beaked echidnas () a novel evaporative window, along with thermal windows, and demonstrate the insulating properties of the...
We identify for wild, free-living short-beaked echidnas () a novel evaporative window, along with thermal windows, and demonstrate the insulating properties of the spines, using infrared thermography. The moist tip of their beak, with an underlying blood sinus, functions as a wet bulb globe thermometer, maximizing evaporative heat loss via an evaporative window. The ventral surface and insides of the legs are poorly insulated sites that act as postural thermal windows, while the spines provide flexible insulation (depending on piloerection). These avenues of heat exchange likely contribute to the higher-than-expected thermal tolerance of this species. Our study highlights how technological advances that allow for non-contact measurement of thermal variables allow us to better understand the physiological capacity of animals in their natural environment.
Topics: Animals; Tachyglossidae; Environment; Body Temperature Regulation; Hot Temperature; Beak
PubMed: 36651031
DOI: 10.1098/rsbl.2022.0495 -
The Journal of Allergy and Clinical... May 2024Early recognition of perioperative anaphylaxis, a life-threatening, usually IgE-mediated, immediate hypersensitivity, is essential, but bedside diagnosis is not always...
BACKGROUND
Early recognition of perioperative anaphylaxis, a life-threatening, usually IgE-mediated, immediate hypersensitivity, is essential, but bedside diagnosis is not always straightforward because clinical presentation may vary.
OBJECTIVES
To describe early characteristics of perioperative immediate hypersensitivity, with special attention to cutaneous phenotypes, and identify risk factors for IgE-mediated allergy.
METHODS
We retrospectively analyzed data from adults with suspected perioperative immediate hypersensitivity who were investigated in two academic medical centers. Multivariable logistic regression was conducted to evaluate associations among patient, clinical, and paraclinical characteristics and IgE-mediated allergy.
RESULTS
Of 145 enrolled patients, 99 (68.3%) and 46 (31.7%) were respectively categorized in the IgE-mediated allergy and non-allergy groups. Cutaneous vasoconstriction phenotype (pallor, piloerection, thelerethism, and sweating with or without cyanosis) occurring within minutes (or even 1 minute) of drug exposure was strongly associated with IgE-mediated allergy (adjusted odds ratio [aOR] = 28.02; 95% CI, 4.41-305.18). IgE-mediated allergy was always life-threatening in this setting. Other early factors associated with allergy were low end-tidal carbon dioxide 25 mm Hg or less (aOR = 5.45; 95% CI, 2.39-26.45), low mean arterial pressure 60 mm Hg or less (aOR = 3.82; 95% CI, 1.28-17.31), and early cutaneous vasodilation (erythema, urticaria, and/or angioedema) (aOR = 2.78; 95% CI, 0.73-20.54). Late cutaneous vasodilation after restoration of hemodynamics corroborated the diagnosis of allergy (aOR = 23.67; 95% CI, 4.94-205.09). The best-fit model including three readily available variables (cutaneous phenotype involving the three modalities [reference lack of cutaneous signs], low mean arterial pressure, and low end-tidal carbon dioxide) had an area under the curve of 0.91.
CONCLUSIONS
Cutaneous vasoconstriction phenotype is associated with the strongest risk of life-threatening allergy and thus may be regarded as pathognomonic of perioperative IgE-mediated anaphylaxis.
Topics: Humans; Male; Female; Middle Aged; Immunoglobulin E; Retrospective Studies; Adult; Aged; Perioperative Period; Risk Factors; Anaphylaxis; Hypersensitivity, Immediate; Vasoconstriction
PubMed: 38378094
DOI: 10.1016/j.jaip.2024.02.009 -
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 -
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 -
Nutrients Feb 2023Endotoxemia is a condition caused by increasing levels of lipopolysaccharide (LPS) characterized by an impaired systemic response that causes multiple organ dysfunction....
Endotoxemia is a condition caused by increasing levels of lipopolysaccharide (LPS) characterized by an impaired systemic response that causes multiple organ dysfunction. ATCC 9595 is a strain with probiotic potential which shows immunomodulatory properties. The incorporation of this bacterium in food rich in bioactive compounds, such as cupuaçu juice (), could result in a product with interesting health properties. This work evaluated the effects of the oral administration of cupuaçu juice fermented with on the outcome of LPS-induced endotoxemia in mice. C57BL/6 mice (12/group) received oral doses (100 µL) of saline solution and unfermented or fermented cupuaçu juice (10 CFU/mL). After 5 days, the endotoxemia was induced by an intraperitoneal injection of LPS (10 mg/kg). The endotoxemia severity was evaluated daily using a score based on grooming behavior, mobility, presence of piloerection, and weeping eyes. After 6 h and 120 h, the mice (6/group) were euthanized for analysis of cell counts (in peritoneal lavage and serum) and organ weight. grew in cupuaçu juice and produced organic acids without the need for supplementation. The bacteria counts were stable in the juice during storage at 4 °C for 28 days. The fermentation with ATCC 9595 changed the metabolites profile of cupuaçu juice due to the biotransformation and enhancement of some compounds. In general, the administration of -fermented juice allowed a significant improvement in several characteristics of endotoxemic status (weight loss, hypothermia, severity index, cell migration). In addition, treatment with fermented juice significantly reduced the weight of the spleen, liver, intestine, and kidneys compared to the saline-treated endotoxemic group. Taken together, our data show that short-term intake therapy of cupuaçu juice fermented with ATCC 9595 can reduce systemic inflammation in an experimental model of LPS-induced endotoxemia in mice.
Topics: Animals; Mice; Lacticaseibacillus rhamnosus; Lipopolysaccharides; Cacao; Lacticaseibacillus; Endotoxemia; Mice, Inbred C57BL; Probiotics; Fermentation
PubMed: 36839417
DOI: 10.3390/nu15041059