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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 -
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 -
Animals : An Open Access Journal From... Apr 2024The highly virulent RH strain is maintained through successive passages in mice, but there is still a lack of studies that refine these procedures from a 3Rs...
The highly virulent RH strain is maintained through successive passages in mice, but there is still a lack of studies that refine these procedures from a 3Rs perspective, where humanitarian ideals aim to minimize the stress, pain, or suffering of the animals used in the research without the loss of results. The aim of this study was to establish humane endpoints in Swiss Webster mice inoculated with the RH strain. A total of 52 mice were infected with 5 × 10 tachyzoites/mL and monitored for periods of up to 5 days. The parameters body weight; hair condition; higher than normal body temperature; hypothermia; respiratory function; pain; soft stools or diarrhea; bloody diarrhea; tense, nervous, or in distress during handling; and ascites were recorded daily in score tables. The results showed that prominent piloerection, respiratory function, pain parameters, and ascites are important clinical signs to be used as a cut-off point for implementing euthanasia. The application of this refinement method helped to avoid animal suffering and pain without compromising the number of parasites recovered. We therefore suggest adopting these parameters in research protocols that require the maintenance of the RH strain in murine models to avoid and reduce animal suffering.
PubMed: 38731332
DOI: 10.3390/ani14091326 -
PLoS Pathogens Dec 2021Kyasanur Forest disease virus (KFDV) and the closely related Alkhurma hemorrhagic disease virus (AHFV) are emerging flaviviruses that cause severe viral hemorrhagic...
Kyasanur Forest disease virus (KFDV) and the closely related Alkhurma hemorrhagic disease virus (AHFV) are emerging flaviviruses that cause severe viral hemorrhagic fevers in humans. Increasing geographical expansion and case numbers, particularly of KFDV in southwest India, class these viruses as a public health threat. Viral pathogenesis is not well understood and additional vaccines and antivirals are needed to effectively counter the impact of these viruses. However, current animal models of KFDV pathogenesis do not accurately reproduce viral tissue tropism or clinical outcomes observed in humans. Here, we show that pigtailed macaques (Macaca nemestrina) infected with KFDV or AHFV develop viremia that peaks 2 to 4 days following inoculation. Over the course of infection, animals developed lymphocytopenia, thrombocytopenia, and elevated liver enzymes. Infected animals exhibited hallmark signs of human disease characterized by a flushed appearance, piloerection, dehydration, loss of appetite, weakness, and hemorrhagic signs including epistaxis. Virus was commonly present in the gastrointestinal tract, consistent with human disease caused by KFDV and AHFV where gastrointestinal symptoms (hemorrhage, vomiting, diarrhea) are common. Importantly, RNAseq of whole blood revealed that KFDV downregulated gene expression of key clotting factors that was not observed during AHFV infection, consistent with increased severity of KFDV disease observed in this model. This work characterizes a nonhuman primate model for KFDV and AHFV that closely resembles human disease for further utilization in understanding host immunity and development of antiviral countermeasures.
Topics: Animals; Chlorocebus aethiops; Cytokines; Disease Models, Animal; Encephalitis Viruses, Tick-Borne; Encephalitis, Tick-Borne; Female; HEK293 Cells; Hemorrhagic Fevers, Viral; Humans; Lymph Nodes; Macaca nemestrina; Vero Cells; Viremia
PubMed: 34855915
DOI: 10.1371/journal.ppat.1009678 -
Journal of Neurology, Neurosurgery, and... Mar 2021To generate a score which clinically identifies surface-directed autoantibodies in adults with new-onset focal epilepsy, and evaluate the value of immunotherapy in this...
OBJECTIVE
To generate a score which clinically identifies surface-directed autoantibodies in adults with new-onset focal epilepsy, and evaluate the value of immunotherapy in this clinical setting.
METHODS
Prospective clinical and autoantibody evaluations in a cohort of 219 consecutive patients with new-onset focal epilepsy.
RESULTS
10.5% (23/219) of people with new-onset focal epilepsy had detectable serum autoantibodies to known or novel cell surface antigenic targets. 9/23 with autoantibodies were diagnosed with encephalitis, by contrast to 0/196 without autoantibodies (p<0.0001). Multivariate analysis identified six features which predicted autoantibody positivity (area under the curve=0.83): age ≥54 years, ictal piloerection, lowered self-reported mood, reduced attention, MRI limbic system changes and the absence of conventional epilepsy risk factors. 11/14 (79%) patients with detectable autoantibodies, but without encephalitis, showed excellent long-term outcomes (modified Rankin Score=0) despite no immunotherapy. These outcomes were superior to those of immunotherapy-treated patients with confirmed autoantibody-mediated encephalitis (p<0.05).
CONCLUSIONS
Seizure semiology, cognitive and mood phenotypes, alongside inflammatory investigation findings, aid the identification of surface autoantibodies among unselected people with new-onset focal epilepsy. The excellent immunotherapy-independent outcomes of autoantibody-positive patients without encephalitis suggests immunotherapy administration should be guided by clinical features of encephalitis, rather than autoantibody positivity. Our findings suggest that, in this cohort, immunotherapy-responsive seizure syndromes with autoantibodies largely fall under the umbrella of autoimmune encephalitis.
Topics: Adolescent; Adult; Aged; Autoantibodies; Cohort Studies; Encephalitis; Epilepsies, Partial; Female; Humans; Immunotherapy; Male; Middle Aged; Nerve Tissue Proteins; Predictive Value of Tests; ROC Curve; Young Adult
PubMed: 33219046
DOI: 10.1136/jnnp-2020-325011 -
Scientific Reports Jan 2021Hair regenerative medicine has emerged as a promising approach for the treatment of severe hair loss. Recent advances in three-dimensional tissue engineering, such as...
Hair regenerative medicine has emerged as a promising approach for the treatment of severe hair loss. Recent advances in three-dimensional tissue engineering, such as formation of hair follicle germs (HFGs), have considerably improved hair regeneration after transplantation in animal models. Here, we proposed an approach for fabricating HFGs containing vascular endothelial cells. Epithelial, dermal papilla, and vascular endothelial cells initially formed a single aggregate, which subsequently became a dumbbell-shaped HFG, wherein the vascular endothelial cells localized in the region of dermal papilla cells. The HFGs containing vascular endothelial cells exhibited higher expression of hair morphogenesis-related genes in vitro, along with higher levels of hair shaft regeneration upon transplantation to the dorsal side of nude mice, than those without vascular endothelial cells. The generated hair follicles represented functional characteristics, such as piloerection, as well as morphological characteristics comparable to those of natural hair shafts. This approach may provide a promising strategy for fabricating tissue grafts with higher hair inductivity for hair regenerative medicine.
Topics: Alopecia; Animals; Cells, Cultured; Endothelium, Vascular; Female; Hair Follicle; Humans; Mice; Mice, Inbred ICR; Mice, Nude; Regeneration; Regenerative Medicine; Stem Cells; Tissue Engineering
PubMed: 33436760
DOI: 10.1038/s41598-020-79722-z -
Toxicology Reports Jun 2024(Fabaceae) crude extracts are key ingredients of several licensed and unlicensed herbal products in East Africa. However, there is limited and often contradicting...
(Fabaceae) crude extracts are key ingredients of several licensed and unlicensed herbal products in East Africa. However, there is limited and often contradicting information regarding its toxicity. We therefore evaluated the acute and subacute toxicity of the ethanolic stem bark extract of in mature healthy Wistar albino rats following Lorke's method and OECD guidelines 407. The LD of the ethanolic stem bark extract of was 2000 mg/kg. The acute toxicity signs observed included piloerection, hyperventilation, lethargy, and loss of righting reflex. There was a significant increase in aspartate aminotransferase, alkaline phosphatase, red blood cells and haemoglobin in rats after 28 days at the dose of 500 mg/kg. Histological analyses revealed multifocal random parenchymal necrosis and scattered periportal mononuclear inflammatory cells infiltration in the liver, interstitial nephritis in the kidney and multifocal lymphoid accumulation in the peribronchiolar and perivascular lung tissue at 500 mg/kg. The ethanolic stem bark of was therefore moderately toxic to the rats when administered in a single high oral dose within 24 h. The extract caused a dose dependent toxicity with significant damage to the kidney, liver and lung tissues at a dose of 500 mg/kg after 28 days. Herbal medicines containing extracts should be consumed cautiously due to likelihood of toxicity particularly at higher doses greater than 500 mg/kg.
PubMed: 38304700
DOI: 10.1016/j.toxrep.2024.01.005 -
Case Reports in Neurology 2021Autonomic status epilepticus (Aut SE) is a condition characterized by ongoing focal autonomic seizure lasting for >30 min. Aut SE can show a variety of clinical...
Autonomic status epilepticus (Aut SE) is a condition characterized by ongoing focal autonomic seizure lasting for >30 min. Aut SE can show a variety of clinical manifestations including vomiting, nausea, changes in heart rate, piloerection, pupillary abnormalities, and visual abnormalities. Although Aut SE is a common finding in childhood in the context of Panayiotopoulos syndrome, few reports have described this condition during adulthood. In the present report, we describe a case of Aut SE in an adult patient with parasellar meningioma and bilateral frontotemporal epileptiform activity on EEG record.
PubMed: 35111030
DOI: 10.1159/000519944 -
Developmental Psychobiology Sep 2020During infection, sickness behaviors, such as a hunched stance with piloerection, can facilitate host resistance by supporting the generation and maintenance of fever....
During infection, sickness behaviors, such as a hunched stance with piloerection, can facilitate host resistance by supporting the generation and maintenance of fever. Fever, in turn, is mediated by hypothalamic neuroimmune signaling. Sickness behaviors, however, can also be influenced by social stimuli. In this study, guinea pig pups were injected with lipopolysaccharide to simulate a bacterial infection and then exposed to a novel, threatening environment while either with their mother or alone. We found that the presence of the mother suppressed sickness behavior, but enhanced fever, and had no measureable effect on gene expression of hypothalamic mediators of fever. This 3-way dissociation induced by the mother's presence is interpreted in terms of the differential adaptive consequences of behavioral and febrile responses for pups in this situation. The results contribute to a growing literature linking immunological and social processes.
Topics: Animals; Behavior, Animal; Fear; Female; Fever; Gene Expression; Guinea Pigs; Hypothalamus; Illness Behavior; Lipopolysaccharides; Male; Mothers
PubMed: 32115686
DOI: 10.1002/dev.21962