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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 -
Neurological Sciences : Official... Jul 2020Cutaneous autonomic small nerve fibers encompass unmyelinated C-fibers and thinly myelinated Aδ-fibers, which innervate dermal vessels (vasomotor fibers), sweat glands... (Review)
Review
Cutaneous autonomic small nerve fibers encompass unmyelinated C-fibers and thinly myelinated Aδ-fibers, which innervate dermal vessels (vasomotor fibers), sweat glands (sudomotor fibers), and hair follicles (pilomotor fibers). Analysis of their integrity can capture early pathology in autonomic neuropathies such as diabetic autonomic neuropathy or peripheral nerve inflammation due to infectious and autoimmune diseases. Furthermore, intraneural deposition of alpha-synuclein in synucleinopathies such as Parkinson's disease can lead to small fiber damage. Research indicated that detection and quantitative analysis of small fiber pathology might facilitate early diagnosis and initiation of treatment. While autonomic neuropathies show substantial etiopathogenetic heterogeneity, they have in common impaired functional integrity of small nerve fibers. This impairment can be evaluated by quantitative analysis of axonal responses to iontophoretic application of adrenergic or cholinergic agonists to the skin. The axon-reflex can be elicited in cholinergic sudomotor fibers to induce sweating and in cholinergic vasomotor fibers to induce vasodilation. Currently, only few techniques are available to quantify axon-reflex responses, the majority of which is limited by technical demands or lack of validated analysis protocols. Function of vasomotor small fibers can be analyzed using laser Doppler flowmetry, laser Doppler imaging, and laser speckle contrast imaging. Sudomotor function can be assessed using quantitative sudomotor axon-reflex test, silicone imprints, and quantitative direct and indirect testing of sudomotor function. More recent advancements include analysis of piloerection (goose bumps) following stimulation of adrenergic small fibers using pilomotor axon-reflex test. We provide a review of the current literature on axon-reflex tests in cutaneous autonomic small fibers.
Topics: Axons; Humans; Nerve Fibers; Reflex; Skin; Sweating
PubMed: 32125538
DOI: 10.1007/s10072-020-04293-w -
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 -
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 -
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 -
Frontiers in Microbiology 2019The aim of this study was to evaluate the effect of a moxifloxacin-loaded organic-inorganic sol-gel with different antibiotic concentration in the biofilm development...
The aim of this study was to evaluate the effect of a moxifloxacin-loaded organic-inorganic sol-gel with different antibiotic concentration in the biofilm development and treatment against , , and , cytotoxicity and cell proliferation of MC3T3-E1 osteoblasts; and its efficacy in preventing the prosthetic joint infection (PJI) caused by clinical strains of and using an murine model. Three bacterial strains, ATCC 35984, 15981, and, ATCC 25922, were used for microbiological studies. Biofilm formation was induced using tryptic-soy supplemented with glucose for 24 h, and then, adhered and planktonic bacteria were estimated using drop plate method and absorbance, respectively. A 24-h-mature biofilm of each species growth in a 96-well plate was treated for 24 h using a MBECTM biofilm Incubator lid with pegs coated with the different types of sol-gel, after incubation, biofilm viability was estimated using alamrBlue. MC3T3-E1 cellular cytotoxicity and proliferation were evaluated using CytoTox 96 Non-Radioactive Cytotoxicity Assay and alamarBlue, respectively. The microbiological studies showed that sol-gel coatings inhibited the biofilm development and treated to a mature biofilm of three evaluated bacterial species. The cell studies showed that the sol-gel both with and without moxifloxacin were non-cytotoxic and that cell proliferation was inversely proportional to the antibiotic concentration containing by sol-gel. In the study, mice weight increased over time, except in the -infected group without coating. The most frequent symptoms associated with infection were limping and piloerection; these symptoms were more frequent in infected groups with non-coated implants than infected groups with coated implants. The response of moxifloxacin-loaded sol-gel to infection was either total or completely absent. No differences in bone mineral density were observed between groups with coated and non-coated implants and macrophage presence lightly increased in the bone grown directly in contact with the antibiotic-loaded sol-gel. In conclusion, moxifloxacin-loaded sol-gel coating is capable of preventing PJI caused by both Gram-positive and Gram-negative species.
PubMed: 32010069
DOI: 10.3389/fmicb.2019.02935 -
Journal of the American Association For... Mar 2020Objectively recognizing postoperative pain in mice is challenging, making it difficult to determine an appropriate postoperative analgesic regimen. Adult male mice...
Objectively recognizing postoperative pain in mice is challenging, making it difficult to determine an appropriate postoperative analgesic regimen. Adult male mice produce ultrasonic vocalizations after exposure to adult female urine (FiUSV). To determine if FiUSV can be used as a indicator of postoperative pain, FiUSV produced by male C57BL/6J mice were assessed for 5 d before and after vasectomy or sham surgery with or without sustained-release buprenorphine. Postoperative pain was assessed by monitoring vocalization using an ultrasonic microphone and by evaluating orbital tightness, posture, and piloerection at postoperative time points. Before vasectomy or sham surgery, 25 of 38 male mice produced FiUSV on 4 of 5 d (143 ± 93 FiUSV). Vasectomized mice without postoperative analgesia produced significantly fewer FiUSV (59 ± 26 FiUSV) compared with baseline (212 ± 102 FiUSV) at 4 h postoperatively, but returned to baseline by 28 h. Vasectomized mice treated with buprenorphine and sham-surgery mice had no change in FiUSV from baseline at any time point after surgery. Activity was decreased compared with baseline in vasectomized mice, regardless of receiving postoperative analgesia or not, but only at the 4-h time point. There were no differences in behavior scores between vasectomized mice and sham-surgery mice at any time point. These results show that FiUSV can be used to detect postoperative pain in male C57BL/6J mice after vasectomy.
Topics: Analgesics, Opioid; Animals; Buprenorphine; Female; Humans; Male; Mice; Mice, Inbred C57BL; Pain Measurement; Pain, Postoperative; Postoperative Period; Ultrasonics; Vasectomy; Vocalization, Animal
PubMed: 31918790
DOI: 10.30802/AALAS-JAALAS-19-000059