Baseline Latency Research Articles

Inhibitory effect of berberine on morphine tolerance and hyperalgesia in mice.

To evaluate the effect of berberine on morphine analgesia, tolerance, and hyperalgesia. Morphine-induced acute tolerance model: mice received intraperitoneal berberine at doses of 2.5, 5.0, and 10 mg/kg; 30 min later, subcutaneous morphine 10 mg/kg was injected every hour for nine continuous h. Morphine 10 mg/kg alone was administered at 24 and 48 h. Morphine-induced chronic tolerance model: mice received intraperitoneal berberine 2.5, 5.0, and 10 mg/kg; 30 min later, 10 mg/kg morphine was injected subcutaneously for eight consecutive days. On the ninth day, morphine 10 mg/kg was given alone. Morphine-induced established tolerance model: mice were injected subcutaneously with morphine 10 mg/kg once a day for eight consecutive days. Berberine 2.5 mg/kg was administered on day one, four, and seven and morphine 10 mg/kg alone on day nine. The baseline latency (T0) and post-treatment latency (T1) were determined by the hot plate test, and the maximum possible analgesic effect (MPAE) was calculated. Nitric oxide synthase (NOS) activity and nitric oxide (NO) content in the spinal cord were measured by spectrophotometer. Verification of berberine analgesic effect by blocking N-methyl-D-aspartate (NMDA) receptor: HT-22 and HEK-293 cells transfected with NMDA plasmid were randomly divided into five groups: control group, NMDA group, berberine low-dose, medium-dose, and high-dose groups (5, 10, 20 μmol/L, respectively). Except for the control group, cells were treated with NMDA (HT-22 cells: 20 mmol/L; HEK-293 cells: 50 μmol/L). After 24 h, cell viability was detected by cell counting kit-8. The molecular mechanism between berberine and the NMDA receptor was studied by molecular docking. Berberine 2.5 and 5.0 mg/kg could prolong the analgesic time of morphine. In acute and chronic morphine tolerance models, berberine could inhibit the decrease of MPAE and baseline latency (0.05). In the established tolerance model, berberine could rapidly reverse the decreased MPAE (0.05). The combination of berberine and morphine on day one could effectively inhibit the morphine-induced increase of NOS activity and NO content in the spinal cord (0.05). Berberine significantly increased the cell viability of NMDA-induced nerve injury in HT-22 and HEK-293 cells (0.05). Molecular docking showed that berberine binds to the receptor pocket of NMDA. Berberine could effectively enhance and prolong the duration of morphine analgesia and inhibit the development of morphine-induced tolerance and hyperalgesia. Furthermore, berberine has a certain neuroprotective effect, which may be related to the inhibition of NMDA activity.

Diagnostic accuracy test of quantitative pupillary light reflex as an indicator of increased intracranial pressure in traumatic brain injury patients: a cross-sectional study

Introduction: The gold standard of intracranial pressure (ICP) measurement is an invasive procedure of inserting ICP monitor and one of the limitations of its surrogate, ultrasonography-based (US) optic nerve sheath diameter (ONSD) measurement is operator-dependent. Quantitative pupillary light reflex (PLR) measurement provides objective data promisingly able to predict ICP elevation. The aim of this study was to evaluate diagnostic accuracy of PLR as an indicator of ICP elevation in traumatic brain injury (TBI) patients compared to US-ONSD measurement. Methods: This was a cross-sectional study involving moderate and severe TBI patients aged 18-65 years without any eye lesion, nor medication and illness that may influence PLR. Healthy volunteers were recruited as control group. ONSD and quantitative PLR measurements (baseline diameter, maximum constriction, constriction velocity, latency and amplitude) were assessed to both groups. The Student t-test or Mann-Whitney U-test was used to compare the ONSD and PLR between case and control group. Further analyses were done to determine the sensitivity, specificity and cut-off value of PLR compared to ONSD in case group. Result: ONSD measurements or parameters were significantly different between case and control group (p<0.001), while all PLR parameters were significantly different (p<0.005) except for right eye constriction latency. The baseline diameter of the right eye had the highest accuracy with cut-off value of >3.9 mm (specificity of 100%, sensitivity of 50%). Other PLR components had variable in accuracy. Conclusion: The baseline diameter of the right eye was the most accurate PLR component as an indicator of ICP elevation, represented by ONSD.

Motion Vector Extrapolation for Video Object Detection.

Despite the continued successes of computationally efficient deep neural network architectures for video object detection, performance continually arrives at the great trilemma of speed versus accuracy versus computational resources (pick two). Current attempts to exploit temporal information in video data to overcome this trilemma are bottlenecked by the state of the art in object detection models. This work presents motion vector extrapolation (MOVEX), a technique which performs video object detection through the use of off-the-shelf object detectors alongside existing optical flow-based motion estimation techniques in parallel. This work demonstrates that this approach significantly reduces the baseline latency of any given object detector without sacrificing accuracy performance. Further latency reductions up to 24 times lower than the original latency can be achieved with minimal accuracy loss. MOVEX enables low-latency video object detection on common CPU-based systems, thus allowing for high-performance video object detection beyond the domain of GPU computing.

Photobiomodulation Therapy Restores Olfactory Function Impaired by Photothrombosis in Mouse Olfactory Bulb

An ischemic stroke typically accompanies numerous disorders ranging from somatosensory dysfunction to cognitive impairments, inflicting patients with various neurologic symptoms. Among pathologic outcomes, post-stroke olfactory dysfunctions are frequently observed. Despite the well-known prevalence, therapy options for such compromised olfaction are limited, likely due to the complexity of olfactory bulb architecture, which encompasses both the peripheral and central nervous systems. As photobiomodulation (PBM) emerged for treating ischemia-associated symptoms, the effectiveness of PBM on stroke-induced impairment of olfactory function was explored. Novel mouse models with olfactory dysfunctions were prepared using photothrombosis (PT) in the olfactory bulb on day 0. The post-PT PBM was performed daily from day 2 to day 7 by irradiating the olfactory bulb via an 808 nm laser with a fluence of 40 J/cm2 (325 mW/cm2 for 2 smin per day). The buried food test (BFT) was used to score behavioral acuity in food-deprived mice to assess the olfactory function before PT, after PT, and after PBM. Histopathological examinations and cytokine assays were performed on the mouse brains harvested on day 8. The results from BFT were specific to an individual, with positive correlations between the baseline latency time measured before PT and its alteration at the ensuing stages for both the PT and PT + PBM groups. Also, the correlation analysis in both groups showed highly similar, significant positive relationships between the early and late latency time change independent of PBM, implicating a common recovery mechanism. Particularly, PBM treatment accelerated the recovery of impaired olfaction following PT by suppressing inflammatory cytokines and enhancing both glial and vascular factors (e.g., GFAP, IBA-1, and CD31). PBM therapy during the acute phase of ischemia improves the compromised olfactory function by modulating microenvironments and inflammation status of the affected tissue.

A history of ethanol intake accelerates the development of morphine analgesic tolerance: A protective potential for omega-3 fatty acids.

Adolescence is a critical life period during which significant neurodevelopmental changes occur within the central nervous system. Consistently, substance abuse in this stage has been found to induce persistent changes in brain responsiveness to future drug challenges. Nowadays, heavy episodic alcohol consumption during adolescence, also known as binge-drinking behavior, is a growing concern in modern societies. On the other hand, alcohol is well known to act as a gateway drug, that is, it promotes the individual's craving for consumption of other drugs of abuse. With this in mind, we aimed to assess whether adolescent ethanol exposure could alter the development of tolerance and dependence to morphine, as an available common opioid drug. Tail flick test was used to measure thermal nociceptive changes in adult male Wistar rats undergone ethanol/vehicle exposure during adolescence. Furthermore, morphine withdrawal syndrome was induced by naloxone injection, and behavioral signs were recorded for 20 min. It was found that adolescent ethanol intake facilitates morphine analgesic tolerance and decreases baseline latency; however, the severity of dependence is not significantly altered. Moreover, we found that 15 days of treatment with omega-3 fatty acids (O3) prevents the mentioned ethanol-induced changes suggesting a therapeutic potential for this compound. O3 supplementation, as an inexpensive and noninvasive method, may assist the clinicians to reverse the adverse effect of alcohol binge drinking on adolescents' brains and to reduce the vulnerability to drug exposure in adulthood. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Radiation-induced meningiomas (RIM) in adults: A single-centre retrospective experience

IntroductionRadiotherapy of central nervous system (CNS) is treatment against many paediatric cancers, even if it is a well-recognized risk factor for meningioma formation. An increased risk of developing secondary brain tumors like radiation-induced meningiomas (RIM) is related to irradiated patients. Research questionThis retrospective study aims to present RIM cases treated in a single tertiary-hospital in Greece and compare the results with international literature and cases of sporadic meningiomas. Materials and methodsA single-centre retrospective study of all patients diagnosed between January 2012 and September 2022 with RIM after having been irradiated in CNS for paediatric cancer was undertaken through hospital’s electronic record and clinical notes, identifying baseline demographics and latency period. ResultsThirteen patients were identified with RIM diagnosis after receiving irradiation for Acute Lymphoblastic Leukaemia (69.2%), Premature Neuro-Ectodermal Tumour (23.1%), and Astrocytoma (7.7%). Median age at irradiation was 5 years old and 32 years old at RIM’s presentation. The latent period from irradiation to meningioma diagnosis was 26.23 ​± ​5.96 years. After surgical excision, histopathologic results showed grade I meningiomas in 12 out of thirteen cases, while only one atypical meningioma was diagnosed. ConclusionPatients who underwent CNS-radiotherapy in childhood for any condition have an increased risk of developing secondary brain tumors such as radiation-induced meningiomas. RIMs resemble sporadic meningiomas in symptomatology, location, treatment, and histologic grade. However, long-term follow-up and regular check-ups are recommended in irradiated patients due to short latency period from irradiation to RIM development, which means younger age patients than those with sporadic meningiomas cases.

Long-term Effect of Permanent Demyelination on Axonal Survival in Multiple Sclerosis.

Background and ObjectivesTo investigate the long-term effect of permanent demyelination on axonal attrition by examining an association between intereye asymmetry of the multifocal visual evoked potential (mfVEP) latency delay and subsequent thinning of retinal ganglion cell axons in patients with a long-standing history of unilateral optic neuritis (ON).MethodsOnly patients with a significant degree of chronic demyelination (intereye latency asymmetry >5 ms) were included in this study. The level of optic nerve demyelination was estimated at baseline by the latency delay of mfVEP, while the degree of axonal loss was assessed by thinning of the retinal nerve fiber layer (RNFL) thickness between baseline and follow-up visits. Low-contrast visual acuity (LCVA) was also evaluated at baseline and follow-up. Patients were examined twice with an average interval of 6.1 ± 1.4 years.ResultsFrom 85 examined patients with multiple sclerosis, 28 satisfied inclusion criteria. Latency of the mfVEP was delayed, and RNFL thickness was reduced in ON eyes compared with fellow eyes at both visits. There was significant correlation between latency asymmetry and baseline or follow-up intereye RNFL thickness asymmetry. Intereye asymmetry of LCVA at baseline correlated with baseline latency asymmetry of mfVEP and baseline asymmetry of RNFL thickness. Latency of the mfVEP in ON eyes improved slightly during the follow-up period, whereas latency of the fellow eye remained stable. By contrast, RNFL thickness significantly declined in both ON and fellow eyes during the follow-up period. The rate of RNFL thinning in ON eyes, however, was more than 2 times faster compared with the fellow eyes (p < 0.001). Furthermore, baseline latency asymmetry significantly correlated with the rate of RNFL thinning in ON eyes during the follow-up (p < 0.001), explaining almost half of the variability of temporal RNFL progression. For each millisecond of latency delay (i.e., ∼0.5 mm of demyelination along the optic nerve), temporal RNFL thickness was annually reduced by 0.05%.DiscussionOur study provides clear in vivo evidence that chronic demyelination significantly accelerates axonal loss. However, because this process is slow and its effect is mild, long-term monitoring is required to establish and confidently measure the neurodegenerative consequences of demyelination.

TailTimer: A device for automating data collection in the rodent tail immersion assay.

The tail immersion assay is a widely used method for measuring acute thermal pain in a way which is quantifiable and reproducible. It is non-invasive and measures response to a stimulus that may be encountered by an animal in its natural environment. However, quantification of tail withdrawal latency relies on manual timing of tail flick using a stopwatch, and precise temperatures of the water at the time of measurement are most often not recorded. These two factors greatly reduce the reproducibility of tail immersion assay data and likely contribute to some of the discrepancies present among relevant literature. We designed a device, TailTimer, which uses a Raspberry Pi single-board computer, a digital temperature sensor, and two electrical wires, to automatically record tail withdrawal latency and water temperature. We programmed TailTimer to continuously display and record water temperature and to only permit the assay to be conducted when the water is within ± 0.25°C of the target temperature. Our software also records the identification of the animals using a radio frequency identification (RFID) system. We further adapted the RFID system to recognize several specific keys as user interface commands, allowing TailTimer to be operated via RFID fobs for increased usability. Data recorded using the TailTimer device showed a negative linear relationship between tail withdrawal latency and water temperature when tested between 47–50°C. We also observed a previously unreported, yet profound, effect of water mixing speed on latency. In one experiment using TailTimer, we observed significantly longer latencies following administration of oral oxycodone versus a distilled water control when measured after 15 mins or 1 h, but not after 4 h. TailTimer also detected significant strain differences in baseline latency. These findings valorize TailTimer in its sensitivity and reliability for measuring thermal pain thresholds.

Influences of UGT2B7 rs7439366 and rs12233719 Polymorphisms on Fentanyl Sensitivity in Chinese Gynecologic Patients.

BackgroundThis study discussed potential influences of UDP glucuronosyltransferase family 2 member B7 (UGT2B7) rs7439366 and rs12233719 polymorphisms on fentanyl sensitivity among Chinese gynecologic patients.Material/MethodsUGT2B7 polymorphisms were genotyped by polymerase chain reaction (PCR) and direct sequencing. Before surgery, baseline latency to pain perception (PPLpre) and pain perception latency of the dominant hand (PPLpost) at 3 minutes after injecting fentanyl were measured by cold pressor-induced pain test. Perioperative fentanyl adoption referred to the total of fentanyl administration during and after operation. Intensity of spontaneous pain was appraised adopting 100-mm visual analog scale (VAS). Factorial analysis was performed by Mann-Whitney U test and Kruskal-Wallis H test.ResultsSignificant differences of PPLpost (CC/CT/TT, P=0.038) and preoperative analgesic effect (CC/CT/TT, P=0.028) were discovered between the rs7439366 genotypes. PPLpost was significantly different between the CT and TT groups (P=0.009) and the CC+CT and TT groups (P=0.026). Preoperative analgesic effect was significantly different between the CT and TT groups (P=0.007) and the CC+CT and TT groups (P=0.009). All of the clinical features studied had no close association with rs12233719 SNP.ConclusionsGynecologic patients with rs7439366 TT genotype had significantly lower fentanyl sensitivity than the other 2 genotype carriers.

The ironic effects of stigmatizing smoking: combining stereotype threat theory with behavioral pharmacology.

Public service announcements often create media messages intended to stigmatize negative behaviors to reduce and prevent these behaviors. Drawing on social and cognitive psychology, we hypothesize that stigmatizing messages can create stereotype threat would be associated with shorter latency to first cigarette in the laboratory compared to the control condition. A double-blind, randomized, controlled trial in which participants completed two smoking lapse tasks, one at baseline and one post-intervention/control. An experimental psychopharmacology laboratory in the western United States. A community sample of non-treatment-seeking daily smokers (n=77) received either a stereotype threat (n=39) or neutral/control (n=38) message. Participants received either a stereotype threat message that stigmatized smoking or a control message. The primary outcome measure was participants' ability to delay smoking during the smoking lapse task in the experimental session FINDINGS: The difference in delay time during the experimental session at the point where 50% of each group had smoked was 3minutes. Cox proportional hazard models revealed that participants in the stereotype threat group were significantly less able to delay initiating smoking compared to the control group (hazard ratio=0.504, P=0.010, 95% confidence interval=0.30, 0.85), after controlling for baseline latency to smoke. Messages that elicit negative stereotypes of smokers operated as 'smoking-promoting messages' in the context of our controlled laboratory investigation.

Correlation Between Electroencephalography and Automated Pupillometry in Critically Ill Patients: A Pilot Study.

Electroencephalography (EEG) is widely used in the monitoring of critically ill comatose patients, but its interpretation is not straightforward. The aim of this study was to evaluate whether there is a correlation between EEG background pattern/reactivity to stimuli and automated pupillometry in critically ill patients. Prospective assessment of pupillary changes to light stimulation was obtained using an automated pupillometry (NeuroLight Algiscan, ID-MED, Marseille, France) in 60 adult patients monitored with continuous EEG. The degree of encephalopathy and EEG reactivity were scored by 3 independent neurophysiologists blinded to the patient's history. The median values of baseline pupil size, pupillary constriction, constriction velocity, and latency were collected for both eyes. To assess sensitivity and specificity, we calculated areas under the receiver-operating characteristic curve. The degree of encephalopathy assessed by EEG was categorized as mild (42%), moderate (37%), severe (10%) or suppression-burst/suppression (12%); a total of 47/60 EEG recordings were classified as "reactive." There was a significant difference in pupillary size, constriction rate, and constriction velocity, but not latency, among the different EEG categories of encephalopathy. Similarly, reactive EEG tracings were associated with greater pupil size, pupillary constriction rate, and constriction velocity compared with nonreactive recordings; there were no significant differences in latency. Pupillary constriction rate values had an area under the curve of 0.83 to predict the presence of severe encephalopathy or suppression-burst/suppression, with a pupillary constriction rate of < 20% having a sensitivity of 85% and a specificity of 79%. Automated pupillometry can contribute to the assessment of cerebral dysfunction in critically ill patients.

The analgesic interaction of tramadol and morphine in rats: An isobolographic study.

In order to assess possible synergistic antinociceptive interactions, the analgesic effects of intra-peritoneal tramadol and morphine administered either separately or in combination were determined using tail-flick latency test following exposure to radiant heat in rats. Groups of eight male Sprague-Dawley rats received either tramadol (3.90, 7.00, 12.50, and 22.20 mg kg-1) and morphine (1.26, 2.25, 4.00 and 7.10 mg kg-1) or a combination of tramadol and morphine (4 different combinations). The baseline latency was obtained before drug injection for each rat, then at 15, 30, 45, 60 and 75 min after injection. The effective dose (ED)50 for either tramadol or morphine individually was 11.70 mgkg-1 and 2.26 mg kg-1, respectively. Based on isobolographic analysis, the ED50 values obtained by drug combination were significantly less than the calculated additive values; which indicates that the co-administration of tramadol and morphine produces synergistic antinociception in the radiant heat tail-flick assay. Combination of morphine and tramadol administered intra-peritoneally can be used for the control of acute pain in rats.

Adjustment of the data acquisition window for the assessment of sensorimotor gating mechanisms in rodents

The acoustic startle reflex (ASR) is a short and intense defensive reaction in response to a loud and unexpected acoustic stimulus. The ASR can be modulated through sensorimotor gating processes, such as prepulse inhibition (PPI), a neurological phenomenon in which a weak pre-stimulus inhibits the reaction to a startling stimulus. The reduction of the amplitude of ASR reflects the ability of the CNS to adapt to a salient sensory stimulus when a preceding weaker signal is perceived. Despite its obvious importance for translational research studies, when the data acquisition window is not properly configured, the measurement of ASR may contain artifacts or be incorrect altogether. In this paper, we issue our recommendations for the correct definition of the response window to achieve good-quality ASR/PPI measurements in order to standardize and implement the method across conditions.•Parameters for detection of peak responses need to be carefully configured, otherwise the risk of obtaining unwanted artifacts or high signal-to-noise ratio increases considerably.•Custom settings yield traces with tighter baseline, higher amplitude, and shorter latency compared to factory default settings.•FFT heatmaps show a solid color-correlation when using custom settings, without the appearance of artifacts.

Assessment of Opicinumab in Acute Optic Neuritis Using Multifocal Visual Evoked Potential.

BackgroundMultifocal visual evoked potential (MF-VEP) assesses a wider visual field than full-field VEP (FF-VEP) and potentially offers a more precise analysis of optic nerve injury and repair following optic neuritis. MF-VEP may offer advantages over FF-VEP as an endpoint in clinical trials of remyelinating therapies.ObjectiveMF-VEP testing was used to study changes in visual pathways in 48% of RENEW [phase II, opicinumab (anti-LINGO-1; BIIB033) vs. placebo after first acute unilateral optic neuritis] participants.MethodsThis exploratory MF-VEP RENEW substudy compared mean outcomes at weeks 24 and 32 among participants in the intent-to-treat (ITT; n = 39; 72% female; mean age: 32.3 years) and per-protocol (PP; n = 31; 71% female; mean age: 32.2 years) populations in affected and fellow eye latency from fellow eye baseline latency and affected and fellow eye amplitude from their own baselines. Treatment differences were evaluated using analysis of covariance (week 24) and a mixed-effect model of repeated measures (week 32). Last observation carried forward was used to impute missing data at week 24.ResultsA trend for improvement in affected eye MF-VEP latency with opicinumab versus placebo was seen in the ITT and PP populations at weeks 24 and 32. Both treatment groups in the ITT population experienced partial recovery of amplitude in the affected eye at week 32. Notably, the mean change in fellow eye amplitude at weeks 24 and 32 was − 17.57 and − 31.41 nanovolts (nV) in placebo but only − 0.59 and 1.93 nV in the opicinumab group [differences at weeks 24 and 32: 16.98 nV (p = 0.050) and 33.33 nV (p < 0.01), respectively].ConclusionResults from this substudy showed advantages of MF-VEP over FF-VEP in multicenter studies of central nervous system reparative therapies and provide novel evidence that fellow eye visual pathway amplitude loss occurs after optic neuritis but can potentially be prevented by opicinumab treatment.RegistrationClinicalTrials.gov identifier NCT01721161.

T130. Quantitative sudomotor axon reflex testing in anterior horn cell disorders

Autonomic disturbances in the form of hyperhidrosis, stiffness of fingers and aggravation of motor weakness on exposure to cold(Cold paresis) has been reported in anterior horn cell disorders like early stages of Amyotrophic lateral sclerosis (ALS), Brachial Monomelic Amyotrophy (BMMA) and Distal Bimelic Amyotrophy (DBMA). Quantitative sudomotor axon reflex test (QSART) was done to assess the functional integrity of postganglionic sympathetic sudomotor axons. 25 patients of BMMA, 10 patients with DBMA divided into two groups based on age (Group1: 20–30 years and Group2: 30–40 years) and 10 patients with ALS where recruited for the study and compared with equal cohort of age matched controls. General physical examination and anthropometric measurements were taken before recording. Sudomotor function of the study participants were evaluated by using Q-Sweat device manufactured by WR Medical Electronics. Resting sweat rate was recorded 5 min followed by iontophoretic stimulation. Baseline sweat volume, Total sweat volume and latency time from start of iontophoretic stimulation [acetylcholine-2 mA current strength for 5 min] to sweat response from 4 recording sites were measured. The variances in parameters like age, body weight, both height of both control and disease group were not significantly different and hence comparable. The mean age of BMMA patients: [Group1: 22.8 ± 3.8 and Group2: 33.8 ± 3.2 years] age matched controls - [Group1: 25.4 ± 2.7 and Group2: 35.1 ± 2.8 years]. There was no significant difference in baseline line sweat rate, latency and total sweat volume between controls and patients at four sites viz. Forearm, Proximal leg, Distal leg and Foot in both affected and unaffected limb. There was no significant difference between affected and unaffected limbs in above parameters in patients with BMMA. Similar results were obtained for patients in early stages of ALS (mean age 46.8 ± 3.2 years) and DBMA [Group1: 23.3 ± 4.8 and Group2: 38.0 ± 2.9 years]. Our findings suggests normal functioning of post ganglionic sudomotor fibers in BMMA and DBMA. The highly prevalent autonomic symptoms probably arise due to pre-ganglionic autonomic dysfunction and possibly in the cervical cord.

Sex Associated Differential Expressions of the Alternatively Spliced Variants mRNA of OPRM1 in Brain Regions of C57BL/6 Mouse

Background/Aims: Opiates are potent analgesics but their clinical use is limited by sex-associated side effects, such as drug tolerance, opioid-induced hyperalgesia and withdrawal reaction. OPRM1, as the main receptor of opioids, plays an important role in the pharmacological process of opioids in rodents and human. We have previously investigated OPRM1, the μ opioid receptor gene, which have dozens of alternatively spliced variants probably correlating with opioid-induced effects in brain regions of four inbred mouse strains and demonstrated the strain-specific expressions of these splice variants. Also, within a strain, the regional expression patterns of some of the variants were similar while others were opposite. Thus, we are aiming to seek out the relationship between sex differences and these alternatively spliced variants. Methods: The present studies follow a SYBR green quantitative PCR (qPCR) which we had used before to examine the expression of OPRM1 splice variant mRNAs in selected brain regions of male and female C57BL/6 mice. Sex-associated differences in baseline latency, opioid-induced tolerance, analgesia and addiction were examined and determined by Tail-flick test, jumps and statistical analysis. Results: The mRNA levels of opioid receptor gene splice variants in male and female mice showed significant differences among the brain regions, implying region-specific alternative splicing of the OPRM1 gene, which was consistent with our previous study. More importantly, the complete mRNA expression profiles of the OPRM1 splice variants was also gender-specific, suggesting a sexual influence on OPRM1 alternative splicing. Conclusion: In brief, we put forward that the distinctions among baseline latency, opioid-induced tolerance, analgesia and physical dependence in male and female mice might correlate with sex associated differential expressions of OPRM1 gene.

Anxiolytic activity of ethanolic and aqueous extract of Ficus carica Linn fruits in swiss albino mice

Background: Benzodiazepams are mainly used to treat anxiety but these drugs produce serious adverse effects, hence herbal drugs are preferred. The present study was undertaken to evaluate the anti-anxiety activity of ethanolic and aqueous extract of Ficus carica (FC) Linn fruits in swiss albino mice.Methods: Male swiss albino rats weighing 25-30gms were divided into six groups and six animals in each group. Diazepam (1.0 mg/kg), AEFC (200 and 400 mg/kg) and EEFC (200 and 400 mg/kg) were suspended in 1% gum acacia and administered orally. The EEFC and AEFC (both extracts at 200 and 400mg/kg/p.o) and vehicle were administered for 7 days once daily p.o. and the last dose was given on the 7lh day, 60 min prior to exposure to the experimental paradigms viz., Elevated plus maze, T- maze model and Hole -board model.Results: Both the extracts of FC significantly increased the number of entries into, time spent and rears in the open arms. Also, it increased the percentile ratio of open arm to total arm entries in elevated plus maze. In T- maze, the both the extracts FC showed a significant increase in baseline latency and decrease in escape and avoidance. In the hole-board model a significant increase in the exploratory behavior like head-dipping and line crossing, rearing was observed after treatment with EEFC and AEFC. FC also decreases the nor-adrenaline levels and increase in serotonin and dopamine levels in the brain. These behavioural changes were significantly higher than that produced by the standard anxiolytic drug diazepam.Conclusions: It was concluded that ethanolic and aqueous extracts of Ficus carica fruits having antianxiety activity.

Chromatic pupillography in hemianopia patients with homonymous visual field defects.

The pupil light reflex is considered to be a simple subcortical reflex. However, many studies have proven that patients with isolated occipital lesions with homonymous hemianopia show pupillary hemihypokinesia. Our hypothesis is that the afferent pupillary system consists of two pathways: one via intrinsically photosensitive retinal ganglion cells (ipRGCs), the other running through the normal RGCs via the visual cortex. The purpose of this study was to test the hypothesis of these two separate pupillomotor pathways. 12 patients (59.1±18.8years) with homonymous hemianopia due to post-geniculate lesions of the visual pathway and 20 normal controls (58.6±12.9years) were examined using chromatic pupillography: stimulus intensity was 28lx corneal illumination, stimulus duration was 4.0s, and the stimulus wavelengths were 420±20nm (blue) and 605±20nm (red), respectively. The examined parameters were baseline pupil diameter, latency, and relative amplitudes (absolute amplitudes compared to baseline), measured at maximal constriction, at 3s after stimulus onset, at stimulus offset, and at 3s and 7s after stimulus offset. The relative amplitudes for the red stimulus were significantly smaller for hemianopia patients compared to the normal controls [maximal constriction: 35.6±5.9% (hemianopia) to 42.3±5.7% (normal); p=0.004; 3s after stimulus onset: p=0.004; stimulus offset: p=0.001]. No significant differences in any parameter were found between the two groups using the blue stimulus. The results support the hypothesis that the ipRGC pathway is mainly subcortical, whereas a second, non-ipRGC pathway via the occipital cortex exists.

Influence of refractive error on pupillary dynamics in the normal and mild traumatic brain injury (mTBI) populations

PurposeThere have been several studies investigating static, baseline pupil diameter in visually-normal individuals across refractive error. However, none have assessed the dynamic pupillary light reflex (PLR). In the present study, both static and dynamic pupillary parameters of the PLR were assessed in both the visually-normal (VN) and the mild traumatic brain injury (mTBI) populations and compared as a function of refractive error. MethodsThe VN population comprised 40 adults (22–56 years of age), while the mTBI population comprised 32 adults (21–60 years of age) over a range of refractive errors (−9.00D to +1.25D). Seven pupillary parameters (baseline static diameter, latency, amplitude, and peak and average constriction and dilation velocities) were assessed and compared under four white-light stimulus conditions (dim pulse, dim step, bright pulse, and bright step). The Neuroptics, infrared, DP-2000 binocular pupillometer (30Hz sampling rate; 0.05mm resolution) was used in the monocular (right eye) stimulation mode. ResultsFor the majority of pupillary parameters and stimulus conditions, a Gaussian distribution best fit the data, with the apex centered in the low myopic range (−2.3 to −4.9D). Responsivity was reduced to either side of the apex. ConclusionsOver a range of dynamic and static pupillary parameters, the PLR was influenced by refractive error in both populations. In cases of high refractive error, the PLR parameters may need to be compensated for this factor for proper categorization and diagnosis.

Compound motor action potential duration and latency are markers of recurrent laryngeal nerve injury.

Compound motor action potential (CMAP) can quantitatively evaluate innervation following injury to the recurrent laryngeal nerve (RLN) in canines. CMAP duration (the total time of CMAP) and latency (the time between the nerve impulse and the onset of action potentials) have not been assessed following RLN injury. Animal study. Twelve canine hemilaryngeal preparations were investigated. Baseline CMAP duration and latency were derived. Group A (n = 5) underwent RLN stretch injury, and group B (n = 7) underwent RLN transection/repair. The change in CMAP duration and latency was assessed between the baseline and 6-month measurements using receiver operator characteristic (ROC) curves for each group individually and combined. Six months following injury, transection/repair injuries had the most significant increase in CMAP duration (2.8 ± 0.6 ms vs. 4.2 ± 0.8 ms, difference 1.4 ms 95% confidence interval [CI]: 0.43 to 2.40) and latency (2.6 ± 0.5 ms vs. 5.6 ± 1.5 ms, difference 3.0 ms 95% CI: 1.65 to 4.38). Stretch injuries also caused an increase in CMAP duration (2.3 ± 0.8 ms vs. 3.0 ± 0.6 ms, difference 0.7 ms 95% CI: -0.49 to 1.77) and latency (2.5 ± 0.8 ms vs. 4.7 ± 1.5 ms, difference 2.3 95% CI: 0.76 to 3.80). Using ROC curves, CMAP duration and latency differentiated between the baseline control and RLN injury at 6 months (area under the curve = 0.78 and 0.98, respectively). CMAP duration and latency are both quantitative measures that may have clinical utility as markers of RLN injury. CMAP latency had superior discrimination between injured and uninjured RLNs. Increased CMAP duration and latency may be explained by incomplete myelination and focal conduction block. NA. Laryngoscope, 127:1855-1860, 2017.