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Evidence-based Complementary and... 2022This study investigated the toxicological implications of a commercial polyherbal formulation, KWAPF01. Twenty-four Wistar rats were randomized into six groups of four...
This study investigated the toxicological implications of a commercial polyherbal formulation, KWAPF01. Twenty-four Wistar rats were randomized into six groups of four animals per group. The animals in Group 1 were administered placebo and designated as control, while the rats in Groups 2 to 6 were administered 1000, 1500, 2000, 2500, and 3000 mg/kg bodyweight single oral dose of KWAPF01, respectively, and subsequently monitored for gross morphological and behavioural changes for 72 h. Piloerection, reduced motility, and tremor were observed in experimental groups, and the median lethal dose (LD) of the extract was 2225.94 mg/kg bodyweight. The 11 compounds identified through HPLC analysis of the extract were docked against acetylcholinesterase (AChE), and the docking scores ranged from -5.3 to -10.8 kcal/mol, with catechol (-5.3 kcal/mol) and berberine (-10.8 kcal/mol) having the highest and lowest binding energies, respectively. Judging by the results, it could be inferred that some of the constituents of KWAPF01 have a direct impact on the nervous system and this is possibly elicited via the cholinergic system as it contains a nicotinic acetylcholine receptors agonist and potential inhibitors of AChE. Therefore, the use of KWAPF01 needs to be cautiously guided.
PubMed: 35873645
DOI: 10.1155/2022/4388941 -
Journal of Neuroimmunology Aug 2020We report six patients with anti-LGI1 associated epilepsy. Two patients presented with new-onset generalized tonic-clonic seizures, four developed faciobrachial dystonic...
We report six patients with anti-LGI1 associated epilepsy. Two patients presented with new-onset generalized tonic-clonic seizures, four developed faciobrachial dystonic seizures and two piloerection. All patients had significant cognitive complaints at the time of diagnosis. All patients described seizure reduction during the first week of carbamazepine, and seizure freedom was obtained at a median of 13 days (range 7-22), sustained after the initiation of immunosuppression. Median time from symptom onset to carbamazepine initiation was 164 days (range 38-206 days). We discuss the particular seizure response to sodium channel blocking antiepileptic drugs, alone or associated with immunosuppression in this antibody mediated seizures.
Topics: Adult; Aged; Ambulatory Care; Anticonvulsants; Autoantibodies; Carbamazepine; Epilepsy; Female; Humans; Intracellular Signaling Peptides and Proteins; Male; Middle Aged; Outpatients; Prospective Studies; Treatment Outcome
PubMed: 32480242
DOI: 10.1016/j.jneuroim.2020.577268 -
Toxins Jan 2020Pinnatoxin G (PnTx-G) is a marine cyclic imine toxin produced by the dinoflagellate , frequently detected in edible shellfish from Ingril Lagoon (France). As other...
Pinnatoxin G (PnTx-G) is a marine cyclic imine toxin produced by the dinoflagellate , frequently detected in edible shellfish from Ingril Lagoon (France). As other pinnatoxins, to date, no human poisonings ascribed to consumption of PnTx-G contaminated seafood have been reported, despite its potent antagonism at nicotinic acetylcholine receptors and its high and fast-acting toxicity after intraperitoneal or oral administration in mice. The hazard characterization of PnTx-G by oral exposure is limited to a single acute toxicity study recording lethality and clinical signs in non-fasted mice treated by gavage or through voluntary food ingestion, which showed differences in PnTx-G toxic potency. Thus, an acute toxicity study was carried out using 3 h-fasted CD-1 female mice, administered by gavage with PnTx-G (8-450 µg kg). At the dose of 220 µg kg and above, the toxin induced a rapid onset of clinical signs (piloerection, prostration, hypothermia, abdominal breathing, paralysis of the hind limbs, and cyanosis), leading to the death of mice within 30 min. Except for moderate mucosal degeneration in the small intestine recorded at doses of 300 µg kg, the toxin did not induce significant morphological changes in the other main organs and tissues, or alterations in blood chemistry parameters. This acute oral toxicity study allowed to calculate an oral LD for PnTx-G equal to 208 g kg (95% confidence limits: 155-281 µg kg) and to estimate a provisional NOEL of 120 µg kg.
Topics: Administration, Oral; Alkaloids; Animals; Female; Intestine, Small; Lethal Dose 50; Marine Toxins; Mice; No-Observed-Adverse-Effect Level; Spiro Compounds
PubMed: 32012834
DOI: 10.3390/toxins12020087 -
Pharmacokinetics and Efficacy of a Long-lasting, Highly Concentrated Buprenorphine Solution in Mice.Journal of the American Association For... Jan 2021Buprenorphine is a commonly used opioid for mitigating pain in laboratory mice after surgical procedures; however, the dosing interval necessary for standard...
Buprenorphine is a commonly used opioid for mitigating pain in laboratory mice after surgical procedures; however, the dosing interval necessary for standard buprenorphine may require treatment every 4 to 6 h to maintain an adequate plane of analgesia. An alternative formulation that provides prolonged plasma concentration with long-lasting effects would be beneficial in achieving steady-state analgesia. We evaluated a long-lasting and highly concentrated formulation of buprenorphine (Bup-LHC) in mice. Pharmacokinetic analysis was performed to assess plasma concentrations in male C57BL/6J (B6) and female CD1 mice after subcutaneous injection of 0.9 mg/kg. The Bup-LHC formulation provided plasma drug levels that exceeded the therapeutic level for at least 12 h in male B6 mice and was below therapeutic levels by 8 h in female CD1 mice. An experimental laparotomy model was used to assess analgesic efficacy. Female CD1 mice were treated with either Bup-LHC (0.9 mg/kg) or saline at 1 h before undergoing an ovariectomy via a ventral laparotomy. At 3, 6, 12, 24, and 48 h after surgery, pain was assessed based on the following behaviors: orbital tightness, grooming, wound licking, rearing, arched posture, ataxia, piloerection, nest building, and general activity. At 3 and 6 h after surgery, Bup-LHC-treated mice had significantly less wound licking and orbital tightness and considerably higher activity levels than did saline-treated mice. At 12 h, wound licking, orbital tightness and activity in Bup-LHC-treated mice were no longer significantly different from those of saline-treated mice. The results of this study suggest that Bup-LHC at 0.9 mg/kg provides sufficient plasma concentrations for analgesia in mice for 6 to 12 h after administration, as demonstrated behaviorally for at least 6 h after surgery.
Topics: Analgesics, Opioid; Animals; Buprenorphine; Female; Male; Mice; Mice, Inbred C57BL; Pain; Pain Measurement
PubMed: 32993847
DOI: 10.30802/AALAS-JAALAS-20-000049 -
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 -
CNS Neuroscience & Therapeutics Sep 2023Ictal piloerection (IP) is an uncommon symptom in focal epilepsy and is associated with autoimmune encephalitis (AE). However, the networks involved in AE-associated IP...
OBJECTIVES
Ictal piloerection (IP) is an uncommon symptom in focal epilepsy and is associated with autoimmune encephalitis (AE). However, the networks involved in AE-associated IP are still unclear. To have a better understanding of IP underlying mechanisms, the current study investigated whole-brain metabolic networks for the analysis of AE-associated IP.
METHODS
Patients with AE and IP diagnosed at our Institute between 2018 and 2022 were selected. We then investigated the brain regions associated with AE-associated IP using positron emission tomography (PET). Anatomometabolic changes (interictal F fluorodeoxyglucose PET) in AE patients with IP were compared with those of AE patients of similar age without IP (p-voxel <0.001, uncorrected).
RESULTS
Sixteen patients showed significant IP. The overall IP prevalence was 4.09% of patients with AE and 12.9% of patients with limbic encephalitis. The most common autoantibodies were against LGI1 (68.8%) followed by GAD65 (6.3%), NMDA (6.3%), GABAb (6.3%), CASPR2 (6.3%), and antibodies recognizing both GAD65 and mGLUR5 (6.3%). Most patients responded well to immunotherapy. Analysis of the imaging results at the voxel level showed that patients with IP had hypermetabolic changes in the right inferior temporal gyrus, suggesting involvement of this brain region in IP.
CONCLUSIONS
Our findings indicate that IP as an uncommon AE-associated manifestations should be recognized. We observed that the metabolic pattern of IP was conspicuous in the right inferior temporal gyrus.
Topics: Humans; Seizures; Encephalitis; Autoantibodies; Autoimmune Diseases of the Nervous System
PubMed: 36971194
DOI: 10.1111/cns.14192 -
Journal of Toxicologic Pathology Jan 2018In this study, we aimed to evaluate changes in the acute toxicity of intraperitoneally administered silver nanoparticles (AgNPs) of varying sizes in BALB/c mice....
In this study, we aimed to evaluate changes in the acute toxicity of intraperitoneally administered silver nanoparticles (AgNPs) of varying sizes in BALB/c mice. Seven-week-old female BALB/c mice were intraperitoneally administered AgNPs measuring 10, 60, or 100 nm in diameter (0.2 mg/mouse) and then sacrificed 1, 3, or 6 h after treatment. In mice administered 10 nm AgNPs, reduced activity and piloerection were observed at 5 h post administration, and lowered body temperature was observed at 6 h post administration, with histopathological changes of congestion, vacuolation, single cell necrosis, and focal necrosis in the liver; congestion in the spleen; and apoptosis in the thymus cortex. These histopathological changes were not evident following administration of either 60 or 100 nm AgNPs. These results suggested that smaller AgNPs, e.g., those measuring 10 nm in diameter, had higher acute toxicity in mice.
PubMed: 29479144
DOI: 10.1293/tox.2017-0043 -
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