Phytochemical profiling of Livistona carinensis leaf extract via UHPLC-QTOF-MS/MS with assessment of its antiviral mechanisms.

Among 36 species of the genus Livistona (family Palmae or Arecaceae), L. carinensis is considered the only species native to Africa. Previous studies showed the richness of Livistona fruits in phenolic compounds. The goal of the current study was to investigate the phytochemical composition and assess the antiviral mechanisms of the L. carinensis leaves' ethanolic extract cultivated in Egypt for the first time. The ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS/MS) was applied. Moreover, the total crude extract was fractionated using ethyl acetate and n-butanol for phytochemical investigations by various chromatographic and spectroscopic techniques. Besides, the antiviral activity of L. carinensis leaves was assessed using three protocols in vitro using MTT assay compared to acyclovir. UHPLC-QTOF-MS/MS-based analysis resulted in identification of 72 metabolites tentatively. They belonged to diverse phytochemical classes, mainly including flavonoids (29), organic acids (10), and phenolic acids (7). The antiviral activity investigations revealed a direct Adeno virus inactivation mechanism rather than inhibition of virus replication or blocking its attachment to Vero cells. Hence, the plant leaves may be a potential candidate for discovery of novel antiviral drugs owing to the diversity of identified phytochemical classes.

A NEW POSTURAL MOTOR RESPONSE TO SPINAL CORD STIMULATION: POST-STIMULATION REBOUND EXTENSION.

Spinal cord stimulation (SCS) has emerged as a therapeutic tool for improving motor function following spinal cord injury. While many studies focus on restoring locomotion, little attention is paid to enabling standing which is a prerequisite of walking. In this study, we fully characterize a new type of response to SCS, a long extension activated post-stimulation (LEAP). LEAP is primarily directed to ankle extensors and hence has great clinical potential to assist postural movements. To characterize this new response, we used the decerebrate cat model to avoid the suppressive effects of anesthesia, and combined EMG and force measurement in the hindlimb with intracellular recordings in the lumbar spinal cord. Stimulation was delivered as five-second trains via bipolar electrodes placed on the cord surface, and multiple combinations of stimulation locations (L4 to S2), amplitudes (50-600 uA), and frequencies (10-40 Hz) were tested. While the optimum stimulation location and frequency differed slightly among animals, the stimulation amplitude was key for controlling LEAP duration and amplitude. To study the mechanism of LEAP, we performed in vivo intracellular recordings of motoneurons. In 70% of motoneurons, LEAP increased at hyperpolarized membrane potentials indicating a synaptic origin. Furthermore, spinal interneurons exhibited changes in firing during LEAP, confirming the circuit origin of this behavior. Finally, to identify the type of afferents involved in generating LEAP, we used shorter stimulation pulses (more selective for proprioceptive afferents), as well as peripheral stimulation of the sural nerve (cutaneous afferents). The data indicates that LEAP primarily relies on proprioceptive afferents and has major differences from pain or withdrawal reflexes mediated by cutaneous afferents. Our study has thus identified and characterized a novel postural motor response to SCS which has the potential to expand the applications of SCS for patients with motor disorders.

Muscle Spasms after Spinal Cord Injury Stem from Changes in Motoneuron Excitability and Synaptic Inhibition, Not Synaptic Excitation.

Muscle spasms are common in chronic spinal cord injury (SCI), posing challenges to rehabilitation and daily activities. Pharmacological management of spasms mostly targets suppression of excitatory inputs, an approach known to hinder motor recovery. To identify better targets, we investigated changes in inhibitory and excitatory synaptic inputs to motoneurons as well as motoneuron excitability in chronic SCI. We induced either a complete or incomplete SCI in adult mice of either sex and divided those with incomplete injury into low or high functional recovery groups. Their sacrocaudal spinal cords were then extracted and used to study plasticity below injury, with tissue from naive animals as a control. Electrical stimulation of the dorsal roots elicited spasm-like activity in preparations of chronic severe SCI but not in the control. To evaluate overall synaptic inhibition activated by sensory stimulation, we measured the rate-dependent depression of spinal root reflexes. We found inhibitory inputs to be impaired in chronic injury models. When synaptic inhibition was blocked pharmacologically, all preparations became clearly spastic, even the control. However, preparations with chronic injuries generated longer spasms than control. We then measured excitatory postsynaptic currents (EPSCs) in motoneurons during sensory-evoked spasms. The data showed no difference in the amplitude of EPSCs or their conductance among animal groups. Nonetheless, we found that motoneuron persistent inward currents activated by the EPSCs were increased in chronic SCI. These findings suggest that changes in motoneuron excitability and synaptic inhibition, rather than excitation, contribute to spasms and are better suited for more effective therapeutic interventions.Significance Statement Neural plasticity following spinal cord injury is crucial for recovery of motor function. Unfortunately, this process is blemished by maladaptive changes that can cause muscle spasms. Pharmacological alleviation of spasms without compromising the recovery of motor function has proven to be challenging. Here, we investigated changes in fundamental spinal mechanisms that can cause spasms post-injury. Our data suggest that the current management strategy for spasms is misdirected toward suppressing excitatory inputs, a mechanism that we found unaltered after injury, which can lead to further motor weakness. Instead, this study shows that more promising approaches might involve restoring synaptic inhibition or modulating motoneuron excitability.

Fracture Strength of Composite Rest Seats: An In Vitro Comparative Study of Different Composite versus Amalgam Restorations.

Occlusal rest provides support for removable partial dentures (RPD). Rest seats are ideally prepared in enamel, but the abutment teeth might be restored or need restorations. This study compared the fracture strength of abutments restored with composite to amalgam restorations after rest seat preparation. Disto-occlusal cavities were prepared in 30 extracted human maxillary premolars. The specimens were allocated in three groups (n = 10) based on the type of restoration. All the specimens were exposed to thermomechanical aging followed by cycling loading. Fracture strength was tested using a universal testing machine, and then, the fracture mode was recorded. The data were analyzed using Kruskal-Wallis test with a significance level set at 0.05. The fracture mode was recorded as catastrophic or non-catastrophic. The fracture strength between all tested groups showed no significant difference. The highest and lowest fracture strength were recorded on amalgam and Tetric N-Ceram groups, respectively. Composite Tetric N-Ceram showed equal distribution of fracture sites on the restorative materials and teeth, it also displayed the highest number of non-catastrophic fractures unlike other groups where the fracture occurred more within the restorations. The fracture strength of composite was comparable to that of amalgam restorations with prepared rest seats.

Hibiscus attenuates renovascular hypertension-induced aortic remodeling dose dependently: the oxidative stress role and Ang II/cyclophilin A/ERK1/2 signaling.

Introduction: The high levels of angiotensin II (Ang II) can modify the vascular tone, enhance vascular smooth muscle cells (VSMCs) proliferation and hypertrophy and increase the inflammatory cellular infiltration into the vessel wall. The old herbal nonpharmacological agent, Hibiscus (HS) sabdariffa L has multiple cardioprotective impacts; thus, we investigated the role of HS extract in amelioration of renovascular hypertension (RVH)-induced aortic remodeling. Materials and methods: Thirty-five rats (7/group) were randomly allocated into 5 groups; group: I: Control-sham group, and RVH groups; II, III, IV, and V. The rats in RVH groups were subjected to the modified Goldblatt two-kidneys, one clip (2K1C) for induction of hypertension. In group: II, the rats were left untreated whereas in group III, IV, and V: RVH-rats were treated for 6 weeks with low dose hibiscus (LDH), medium dose hibiscus (MDH), and high dose hibiscus (HDH) respectively. Results: We found that the augmented pro-contractile response of the aortic rings was ameliorated secondary to the in-vivo treatment with HS dose dependently. The cyclophilin A (CyPA) protein levels positively correlated with the vascular adhesion molecule-1 (VCAM-1) and ERK1/2, which, in turn, contribute to the reactive oxygen species (ROS) production. Daily HS intake modified aortic renovation by enhancing the antioxidant capacity, restraining hypertrophy and fibrosis, downregulation of the metastasis associated lung adenocarcinoma transcript (MALAT1), and cyclophilin A (CyPA)/ERK1/2 levels. Discussion: Adding to the multiple beneficial effects, HS aqueous extract was able to inhibit vascular smooth muscle cell proliferation induced by 2K1C model. Thus, adding more privilege for the utilization of the traditional herbal extracts to attenuate RVH-induced aortopathy.

Knowledge of Saudi dental students and interns towards luting cements and their applications in fixed prosthodontics.

BACKGROUND: Enhancement of students' knowledge is essential in improving their clinical skills and performance. Thus, the curriculum should be prepared to achieve a better outcome. The current study aimed to determine the dental students' and interns' basic knowledge towards dental luting cements and their application in dental practice to improve the theoretical and clinical training sections. MATERIALS AND METHODS: A cross-sectional study was conducted among dental students and interns at three Colleges of Dentistry in the Kingdom of Saudi Arabia between September 2019-June 2020. An online questionnaire was used which included demographic data, questions about luting cement usage, cementation techniques, and commonly used cements in dental clinics. Descriptive analysis and chi-square test were used to show the association between level of dental education and the use of dental cements using SPSS software. The significance level was set at 5%. RESULTS: The total respondents were 626 dental students/interns of whom 78.8% were undergraduate dental students. Participants who reported undergraduate studies as the source of information were 79.7%. The type of restoration was the main factor in luting cement selection (62.6%). Concerning the isolation technique in cementing laminate veneers, 49.7% used dri-angles, cotton rolls and saliva ejectors. Dual-cure resin cement was the most common cement used in all the mentioned restorations except in pressed porcelain laminate veneers and cement-retained implant-supported restorations. CONCLUSIONS: Students' knowledge and practice in managing dental implants and porcelain laminate veneers need to be improved. The selection of a luting agent for a given restoration by students and interns was based on the basic knowledge, available cement, and the type of restoration. Awareness towards the management of short prepared teeth and custom-made cast posts and cores is also limited.

The Toothbrushing Effects on Surface Properties and Color Stability of CAD/CAM and Pressable Ceramic Fixed Restorations-An In Vitro Study.

Pressable ceramic restorations have been introduced and investigated, and found comparable to CAD/CAM ceramic in terms of mechanical properties; however, the effect of toothbrushing on the pressable ceramic has not been thoroughly investigated. The objective of the current study was to assess the effect of artificial toothbrushing simulation on the surface roughness, microhardness, and color stability of different ceramic materials. Three lithium disilicate-based ceramics (IPS Emax CAD [EC], IPS Emax Press [EP]; (Ivoclar Vivadent AG), and LiSi Press [LP] (GC Corp, Tokyo, Japan)) were examined. For each ceramic material, eight bar-shaped specimens were prepared and subjected to 10,000 brushing cycles. Surface roughness, microhardness, and color stability (∆E) were measured before and after brushing. Scanning electron microscopy (SEM) was used for surface profile analysis. The results were analyzed using one-way ANOVA, Tukey's post hoc test, and paired sample t-test α = 0.05. The findings revealed a non-significant decrease in the surface roughness of EC, EP, and LP groups (p > 0.05), and both LP and EP have the lowest surface roughness values (0.64 ± 0.13, 0.64 ± 0.08 µm) after brushing, respectively. Toothbrushing showed a decrease in the microhardness of the three groups: EC and LP, p < 0.001; EP, p = 0.012). EP showed the lowest hardness value after brushing (862.45 ± 273.83). No significant changes (∆E) were observed in all groups (p > 0.05); however, the EC group was found to be considerably affected by color changes, in comparison to the EC and LP groups. Toothbrushing had no effect on surface roughness and color stability of all tested materials, but it decreased the microhardness. Material type, surface treatments, and glazing of ceramic materials contributed to the surface changes in the ceramic materials, necessitating further investigations in terms of the toothbrushing effect with different glazing as variables.

GABA Increases Sensory Transmission In Monkeys.

Sensory input flow is central to voluntary movements. For almost a century, GABA was believed to modulate this flow by inhibiting sensory axons in the spinal cord to sculpt neural inputs into skilled motor output. Instead, here we show that GABA can also facilitate sensory transmission in monkeys and consequently increase spinal and cortical neural responses to sensory inputs challenging our understanding of generation and perception of movement.

Influence of CAD/CAM Milling and 3D-Printing Fabrication Methods on the Mechanical Properties of 3-Unit Interim Fixed Dental Prosthesis after Thermo-Mechanical Aging Process.

This study assessed the influence of CAD/CAM milling and 3D-printing fabrication methods on mechanical properties of 3-unit interim fixed dental prosthesis (IFDPs) after thermo-mechanical aging. Forty 3-unit IFDPs were fabricated on a mandibular right second premolar and second molar of a typodont cast. Samples were fabricated from the following materials; auto-polymerized polymethyl methacrylate (conventional resin), CAD/CAM PMMA (milled resin) and two different CAD/CAM 3D-printed composite resins; digital light processing Asiga (DLP AS) and stereolithography NextDent (SLA ND). Mechanical properties were compared between the studied materials using Kruskal−Wallis test, followed by multiple pairwise comparisons using Bonferroni adjusted significance. There was a significant difference in flexural strength and microhardness between the studied materials (p < 0.001), with the highest mean ± SD reported in the milled IFDPs (174.42 ± 3.39, 27.13 ± 0.52), and the lowest in the conventional IFDPs (98.02 ± 6.1, 15.77 ± 0.32). Flexural strengths differed significantly between the conventional IFDPs and all materials except DLP AS. The highest elastic modulus was recorded in the milled group, and the lowest in the SLA ND group (p = 0.02). In conclusion, superior flexural strength, elastic modulus, and hardness were reported for milled IFDPs. SLA ND printed IFDPs showed comparable mechanical properties to milled ones except for the elastic modulus.

An Updated Review of Salivary pH Effects on Polymethyl Methacrylate (PMMA)-Based Removable Dental Prostheses.

Salivary pH is a neglected factor that may affect the performance of removable dental prostheses (RDP). This study aimed to review literature in reference to the role of salivary pH on the performance of RDP and materials used for their fabrication. From January 1990 until December 2021, a search was done on PubMed, Scopus, and Web of Science databases using removable dental prostheses, salivary pH, PMMA, Denture base, and physical properties as keywords. Articles that met the inclusion criteria (full-length articles have investigated the effect of salivary pH on RDP materials in vitro and in vivo) were included. Out of 433 articles, 8 articles that met the inclusion criteria were included. All studies used artificial saliva with different salivary pH ranging between 3 and 14. Two articles investigated the role of salivary pH on the cytotoxicity of denture base resins and soft liner. One article studied the durability and retention of attachments, one article analyzed the performance of PEEK materials, one article researched the fatigue resistance of a denture base, one article investigated the corrosion of RPD framework cast and milled Co-Cr, one article studied the strength and clasp retention and deformation of acetal and PEEK materials, and one evaluated changes in mass and surface morphology of CAD-CAM fiber-reinforced composites for the prosthetic framework. Different salivary pH affected all included materials in this review except PEEK materials. The most adverse effect was reported with alkaline and acidic; however, the acidic showed the most deterioration effect. Salivary pH has a role in the selection of material used for RDP fabrication.

Comparative Study of the Effectiveness of Laboratory-Formulated Polishing Pastes for Two CAD/CAM Ceramic Restorative Materials.

PURPOSE: To evaluate the effect of different polishing pastes with different particle sizes on the surface finish of two different CAD/CAM ceramics. MATERIALS AND METHODS: A total of 128 specimens were prepared of two CAD/CAM ceramics: lithium disilicate (12.4 × 14.5 × 2 mm) and monolithic zirconia (17.5 × 12.5 × 2.5 mm). They were divided randomly into 8 groups according to surface treatment (n = 8). Group 1 (control) was left as received after crystallization or sintering with no further surface treatment; Group 2 (glazed); Group 3 (positive control), where specimens were polished using standardized surface treatment (medium grit silicon carbide discs, rubber cup and pumice slurry, then rubber cup and toothpaste). For groups 4 to 8, in addition to silicon carbide and pumice slurry polishing, specimens were further polished using a diamond paste (DP), and polishing pastes of microzirconia (MZ), nanosilica (NS), nanodiamond (ND), and nanozirconia (NZ), respectively. Surface roughness (Ra ) was measured using noncontact profilometer. The mean values were compared using ANOVA and Post Hoc Tukey's test (α = 0.05). Specimens' surfaces were studied using a scanning electron microscope (SEM). RESULTS: Positive control group and MZ exhibited significant Ra of lithium disilicate compared to control (p ˂ 0.001), glazed (p = 0.001), DPs (p = 0.002), NS (p ˂ 0.001), ND (p ˂ 0.001), and NZ (p = 0.002). In the case of zirconia, positive control showed a significantly higher Ra compared to all other groups (p ˂ 0.001). No statistical difference was found between all other polishing techniques (positive control, glazed, DPs, NS, ND, MZ, and NZ) (p > 0.05). CONCLUSION: Polishing with ND, NZ, and NS lab-formulated pastes produced surfaces with comparable smoothness to control and glazed specimens for lithium disilicate and zirconia ceramic materials.

Evaluation of the Accuracy of Digital Impressions Obtained from Intraoral and Extraoral Dental Scanners with Different CAD/CAM Scanning Technologies: An In Vitro Study.

PURPOSE: To compare the accuracy of intraoral and extraoral scanners (IOSs and EOSs) with different scanning technologies. MATERIAL AND METHODS: A phantom cast was used to simulate the patient's mouth. Polyether impression was made of the phantom cast and poured to fabricate stone casts. The stone casts were scanned by two IOSs (3shape Trios 3, 3S and Dental Wings, DW) and two EOSs (S600 Arti Zirkonzahn, ZK and Ceramill map 600 Amann Girrbach, AG) to obtain digital casts. Reference teeth (canines, premolar, and molars) dimensions were measured on the digital casts by Geomagic software and compared to measurements of the stone cast done by stereomicroscope. The dimensions were occluso-cervical mesio-distal, and bucco-lingual and their average was calculated. Differences between digital and stereoscopic measurements were assessed using paired t-test. Discrepancies between these measurements were calculated as differences and were compared among the four scanners using ANOVA. RESULTS: The differences among the discrepancies of the four scanners were not significant overall (p = 0.969), in premolars (p = 0.932) or molars (p = 0.069) but significant in canines (p = 0.025). The discrepancies of the EOSs were ≤0.01 mm in canines and molars. DW had the greatest discrepancy in canines and molars. CONCLUSIONS: The IOSs and EOSs had similar accuracy except in canines where EOSs performed better. The accuracy of scanning is affected by the smoothness and regularity of the teeth surfaces as in case of the canine.

Translucency of nanoparticle-reinforced PMMA denture base material: An in-vitro comparative study.

The aim of this study was to assess the translucency of denture base acrylic resin reinforced with zirconium dioxide (ZrO2NPs), silicon dioxide (SiO2NPs), and diamond (DNPs) nanoparticles. A total of 130 heat-polymerized acrylic discs (15×2.5 mm) were fabricated conventionally and divided into control and experimental groups according to nanoparticle type and concentration (0.5, 1, 1.5, and 2.5 wt%). Unmodified acrylic resin specimens served as control. All specimens were thermocycled (5,000 cycles). Translucency was measured using a spectrophotometer. ANOVA and post-hoc Turkeys' test were used for data analysis at α=0.05. The translucency of modified PMMA was significantly lower than control (p<0.05) except 0.5% ZrO2NPs and SiO2NPs (p>0.05) which exhibited the highest translucency values among modified groups. As the NPs concentration increased, the translucency decreased and the lowest value was seen with 2.5% DNPs (1.18±0.10). The addition of ZrO2NPs, SiO2NPs, and DNPs into denture base resin decreased the translucency.

Evaluation of Bacterial Leakage in Platform-Switching Dental Implant with Morse Taper Connection Under Thermocycling and Loading Effects: In Vitro Study.

PURPOSE: The aim of this study was to test in vitro the bacterial microleakage at the Morse taper implant-abutment connection with switched platform subjected to functional load and thermocycling. MATERIALS AND METHODS: A total of 48 Morse taper implant-abutment connections with switched platforms (12 implants per group) were used. The abutments were attached to implants and presented in four groups: group 1, control; group 2, subjected to thermocycling; group 3, subjected to cyclic compressive loading; and group 4, subjected to thermocycling and cyclic compressive loading. All groups were then inoculated in Eppendorf tubes including three types of bacterial suspensions: Enterococcus faecalis, Staphylococcus aureus, and Pseudomonas aeruginosa for 7 and 14 days to detect possibility of bacterial infiltration from outside to the internal chamber of the implant. RESULTS: Implants not exposed to cyclic loading and thermocycling (group 1) and those exposed to thermocycling (group 2) exhibited no infiltration of E faecalis, S aureus, and P aeruginosa from outside to the inner chamber of the implant, while infiltration of P aeruginosa was only observed in implants subjected to cyclic loading only (group 3) and those subjected to cyclic loading in conjunction with thermocycling (group 4). CONCLUSION: Microbial leakage at the implant-abutment connection is influenced by the applied load alone and in combination with thermocycling; however, E faecalis and S aureus did not leak at the implant-abutment connection even under these circumstances. Only P aeruginosa infiltrated inside the implant-abutment connection, which might be caused by its swarming motility.

The Mechanistic Basis for Successful Spinal Cord Stimulation to Generate Steady Motor Outputs.

Electrical stimulation of the spinal cord is a promising rehabilitation intervention to restore/augment motor function after spinal cord injury (SCI). Combining sensory feedback with stimulation of remaining motor circuits has been shown to be a prerequisite for the functional improvement of SCI patients. However, little is known about the cellular mechanisms potentially underlying this functional benefit in the injured spinal cord. Here, we combine computer simulations with an isolated whole-tissue adult mouse spinal cord preparation to examine synaptic, cellular, and system potentials measured from single motoneurons and ventral roots. The stimulation protocol included separate and combined activation of the sensory inputs (evoked by dorsal root stimulation) and motor inputs (evoked by stimulation of spinal cord tissue) at different frequencies, intensities, and neuromodulatory states. Our data show that, while sensory inputs exhibit short-term depression in response to a train of stimulation, motor inputs exhibit short-term facilitation. However, the concurrent activation of both inputs elicits a stronger and steadier motor output. This effect is enhanced by the application of pharmacological neuromodulators. Furthermore, sensorimotor excitatory postsynaptic potentials (EPSPs) summate sublinearly (i.e., their combination produces an excitatory potential smaller than the sum of the excitatory potentials they would individually produce). However, ventral root compound action potentials (CoAPs) summate supralinearly generating much higher outputs. Computer simulations revealed that the contrasting summation and disproportionality in plasticity between the excitatory postsynaptic potentials (EPSPs) and CoAPs result from the motoneuronal firing threshold acting as an amplitude-selective filter. Together, these results provide the mechanistic basis for the cellular processes contributing to the generation of steady motor outputs using spinal stimulation. This data has great potential to guide the design of more effective stimulation protocols in SCI patients.

Nutritional and biological evaluation of Phoenix canariensis pollen grains

ABSTRACT The nutritional value of pollens of Phoenix canariensis Chabaud, Arecaceae, was evaluated. HPLC analysis of vitamins revealed the predominant presence of vitamin C (109.13 ppm), followed by vitamin A (53.71 ppm) and vitamin E (40.60 ppm) and the total carbohydrates (28.12%), proteins (17.10%). In addition, 16 amino acids of which nine are essential (75.07%), and seven are non-essential (24.93%) were determined. On the other hand, two steroidal saponins (dioscin and methyl protodioscin) were isolated from the pollens, their structures were elucidated by spectroscopic techniques, including 1H NMR and 13C NMR. Their content in the 70% ethanolic extract was quantified using reversed phase HPLC and found to be 0.013% and 19.35%, respectively. The modulatory effect of the isolated compounds on the prevention of benign prostatic hyperplasia induced in rats and their moderate curative effect on stressed testicular tissue were studied. Being a good source of carbohydrates, proteins, vitamins, and amino acids pollens of P. canariensis can be used as a promising source of dietary supplement. Meanwhile pollens can act as prophylactic agent against benign prostatic hyperplasia.

Modulation of SK channels regulates locomotor alternating bursting activity in the functionally-mature spinal cord.

The spinal cord contains specialized groups of cells called pattern generators, which are capable of orchestrating rhythmic firing activity in an isolated preparation. Different patterns of activity could be generated in vitro including right-left alternating bursting and bursting in which both sides are synchronized. The cellular and network mechanisms that enable these behaviors are not fully understood. We have recently shown that Ca2+-activated K+ channels (SK channels) control the initiation and amplitude of synchronized bursting in the spinal cord. It is unclear, however, whether SK channels play a similar role in the alternating rhythmic pattern. In the current study, we used a spinal cord preparation from functionally mature mice capable of weight bearing and walking. The present results extend our previous work and show that SK channel inhibition initiates and modulates the amplitude of alternating bursting. We also show that addition of methoxamine, an α1-adrenergic agonist, to a cocktail of serotonin, dopamine, and NMDA evokes robust and consistent alternating bursting throughout the cord.

Comparative chemical and biological studies of leaves and pollens of Phoenix canariensis hort. ex Chabaud.

AIM: Phoenix canariensis hort. ex Chabaud is one of the most important palm plants. In spite of that, it has not been extensively investigated from a phytochemical or a biological perspective. MATERIALS & METHODS: Air-dried powdered leaves and pollen grains of the plant were extracted using 70% ethanol. The residues were fractionated with different solvents of increasing polarity. Antioxidant, anti-inflammatory, hepatoprotective, anti-hyperglycemic activities were determined using adult male albino rats of wistar strain. RESULTS: Phytochemical investigation of Phoenix canariensis (Arecaceae) leaves and pollens led to the isolation of five compounds; isorhamnetin-3-O-ß-glucoside and isorhamnetin 7-O-rutinoside from the leaves in addition to isorhamnetin-3-O-rutinoside and rutin together with ß sitosterol-3-O-ß-D-glucoside from pollens. The 70% ethanolic extracts of both organs were found to possess the highest antioxidant activity followed by their ethyl acetate fractions. Seventy percent ethanolic leaf extract and its ethyl acetate fraction showed the most potent hepatoprotective, anti-inflammatory and anti-hyperglycemic activities as compared with reference drugs. Isorhamnetin-7-O-rutinoside and ß-sitosterol-3-O-ß-D-glucoside were isolated from the genus and from Phoenix canariensis for the first time. CONCLUSION: This study reveals that Phoenix canariensis is an efficient natural source of safe antioxidants, anti-hyperglycemic, anti-inflammatory and hepatoprotective agents.

SK channel inhibition mediates the initiation and amplitude modulation of synchronized burst firing in the spinal cord.

Burst firing in motoneurons represents the basis for generating meaningful movements. Neuromodulators and inhibitory receptor blocker cocktails have been used for years to induce burst firing in vitro; however, the ionic mechanisms in the motoneuron membrane that contribute to burst initiation and amplitude modulation are not fully understood. Small conductance Ca2+-activated potassium (SK) channels regulate excitatory inputs and firing output of motoneurons and interneurons and therefore, are a candidate for mediating bursting behavior. The present study examines the role of SK channels in the generation of synchronized bursting using an in vitro spinal cord preparation from adult mice. Our results show that SK channel inhibition is required for both initiation and amplitude modulation of burst firing. Specifically, administration of the synaptic inhibition blockers strychnine and picrotoxin amplified the spinal circuit excitatory drive but not enough to evoke bursting. However, when SK channels were inhibited using various approaches, the excitatory drive was further amplified, and synchronized bursting was always evoked. Furthermore, graded SK channel inhibition modulated the amplitude of the burst in a dose-dependent manner, which was reversed using SK channel activators. Importantly, modulation of neuronal excitability using multiple approaches failed to mimic the effects of SK modulators, suggesting a specific role for SK channel inhibition in generating bursting. Both NMDA (N-methyl-d-aspartate) and AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionate) receptors were found to drive the synchronized bursts. The blocking of gap junctions did not disturb the burst synchrony. These results demonstrate a novel mechanistic role for SK channels in initiating and modulating burst firing of spinal motoneurons.NEW & NOTEWORTHY This study demonstrates that cholinergic inhibition or direct blockade of small conductance Ca2+-activated potassium (SK) channels facilitates burst firing in spinal motoneurons. The data provide a novel mechanistic explanation for synchronized bursting initiation and amplitude modulation through SK channel inhibition. Evidence also shows that synchronized bursting is driven by NMDA (N-methyl-d-aspartate) and AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionate) receptors and that gap junctions do not mediate motoneuron synchronization in this behavior.