Partial Α2 Research Articles

Effect of Oral Clonidine on Epidural Anaesthesia in Hip Replacement Surgery

Background: Analgesia, sedation, hemodynamic stability, and improved postoperative outcomes are important for orthopedic surgery. Researchers have found clonidine, a centrally acting partial α2 adrenoceptor agonist serves this well. This study was conducted to find out the effect of oral clonidine on epidural anesthesia in hip replacement surgery.Methods: This open-level, randomized control trial (RCT) was conducted at the Department of Anesthesia, Analgesia, and Intensive Care Medicine, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka. A total of 60 patients were included in the trial; 30 in the Intervention (clonidine) group and another 30 in the control group (placebo). Sensory block, motor block, visual analog scale (VAS), and vital parameters were assessed. Ethical approval was taken from the institutional review board (IRB) of BSMMU and informed written consent was taken from each participant.Results: The onset of sensory blockade was significantly quick (intervention group vs control group:15.8±1.3 min vs 19.4±2.0 min) and analgesia sustained significantly for a prolonged period (p-value: 0.003) higher in the intervention group (256.1±18.7 min) than the control group (192.9±16.1 min). After 5 and 10 minutes of intervention; significantly (p-value: 0.001) lower systolic blood pressure was observed in the intervention group. And in 15 and 45 minutes, diastolic blood pressure was significantly (p-value: 0.013, 0.001; respectively) higher in the intervention group.Conclusion: Oral clonidine gave early onset and prolonged duration of sensory blocking, analgesia without major hemodynamic instability, and post-operative side effects.

Structural and dynamical investigation of histone H2B in well-hydrated nucleosome core particles by solid-state NMR

H2A-H2B dimer is a key component of nucleosomes and an important player in chromatin biology. Here, we characterized the structure and dynamics of H2B in precipitated nucleosome core particles (NCPs) with a physiologically relevant concentration using solid-state NMR. Our recent investigation of H3-H4 tetramer determined its unique dynamic properties and the present work provides a deeper understanding of the previously observed dynamic networks in NCP that is potentially functionally significant. Nearly complete 13C, 15N assignments were obtained for H2B R30-A121, which permit extracting unprecedented detailed structural and amino-acid site-specific dynamics. The derived structure of H2B in the well-hydrated NCP sample agrees well with that of X-ray crystals. Dynamics at different timescales were determined semi-quantitatively for H2B in a site-specific manner. Particularly, higher millisecond-microsecond dynamics are observed for H2B core regions including partial α1, L1, partial α2, and partial L3. The analysis of these regions in the context of the tertiary structure reveals the clustering of dynamical residues. Overall, this work fills a gap to a complete resonance assignment of all four histones in nucleosomes and delineates that the dynamic networks in NCP extend to H2B, which suggests a potential mechanism to couple histone core with distant DNA to modulate the DNA activities.

Clinical evaluation of dexmedetomidine versus clonidine as an adjuvant to bupivacaine in subarachnoid block for gynecological procedure

Background and Aim: Clonidine is a partial α2 adrenergic agonist used intrathecally with well-established efficacy and safety profile with effective prolongation of both motor and sensory spinal blockade. Dexmedetomidine, another member of α2 agonist’s family, is recently being introduced in Indian market and is approved as an intravenous sedative and co-analgesic drug. This study examines and compares the usefulness and safety of dexmedetomidine versus clonidine as an adjuvant to bupivacaine in subarachnoid block for gynecological vaginal surgeries. Material and Methods: Hundred patients, aged 30-60 years of ASA Physical status I and II, scheduled for elective gynecological vaginal surgery were enrolled in this study. Patients were randomly allocated to one of the two groups of 50 patients each by distributing sealed envelopes. Group C (n=50) received 0.5% hyperbaric Bupivacaine 2.5ml + 0.5ml distilled water containing 30µgm clonidine intrathecally. Group D (n=50) received 0.5% hyperbaric Bupivacaine 2.5ml +0.5ml distilled water containing 5µg Dexmedetomidine intrathecally. The sensory block was assessed by skin sensation to pin prick. The motor block was assessed according to the Modified Bromage Scale. Hemodynamic variables were recorded at 1, 3, 5, 10, 15, 20, 30 minutes and then at 15 minutes interval throughout the surgical period.

Clinical Efficacy Of Hyperbaric Bupivacaine With Clonidine In Two Different Doses With Respect To Sensory Characteristics, Motor Characteristics And Recovery Characteristics In Patients Undergoing Lower Limb Orthopaedic Surgeries

Background: Intrathecal opiods as adjuvant to local anaesthetics, when administered intrathecally, act synergistically to overcome the property of reduced duration of postoperative analgesia.. Clonidine a selective partial α2 adrenergic agonist administered intrathecally with bupivacaine improved the quality and duration of postoperative analgesia. Methods: In this Randomised comparative study, 60 patients aged between 20 years and 60 years belonging to ASA I and II undergoing lower limb Orthopaedic surgeries were selected. Sample size was calculated by keeping the confidence interval at 95% and power of study at 80%. Results: The mean time of onset of sensory, motor blockade and the time to achieve maximum sensory level and sedation scores was compared in both the groups. The mean duration of effective analgesia in Group BC30 and in Group BC60 was 357.33±6.915 and 425.33±27.131 minutes respectively. Conclusion: In conclusion , the addition of clonidine 60 µg to hypaerbaric bupivacaine intrathecally prolonged both sensory and motor blocked with higher duration of sensory block when compared to motor block of spinal anaesthesia and hence the duration of analgesia when comared to clonidine 30µg .

Reduction in ultraviolet B light-induced erythema by oxymetazoline and brimonidine is mediated by different α-adrenoceptors.

When applied topically, oxymetazoline and brimonidine reduce the persistent facial erythema of rosacea; this effect is mediated by cutaneous vasoconstriction induced by postsynaptic activation of α-adrenoceptors. We investigated the α-adrenergic pharmacology of oxymetazoline and brimonidine. Functional activity on α-adrenoceptors was evaluated in vitro in HEK293 cells stably expressing single receptor subtypes using a fluorometric imaging plate reader Ca2+ influx assay. Oxymetazoline was an α1 -adrenoceptor agonist with partial α2 -adrenoceptor activity, whereas brimonidine was a highly selective full α2 -adrenoceptor agonist. In vivo pharmacology was investigated in a mouse model of ultraviolet B light (UVB)-induced skin erythema. To selectively inhibit α-adrenoceptor subtypes, mice were injected with prazosin (an α1 -selective antagonist) or rauwolscine (an α2 -selective antagonist) following UVB exposure. Oxymetazoline cream 1.0%, brimonidine gel 0.33% or vehicle control was applied topically, and erythema was measured using a chromameter. Oxymetazoline and brimonidine reduced UVB-induced erythema compared with vehicle control (P<.01). The effect of oxymetazoline was impaired in prazosin-pretreated but not rauwolscine-pretreated mice. Conversely, the effect of brimonidine was impaired in rauwolscine-pretreated but not prazosin-pretreated mice. These data suggest that while oxymetazoline and brimonidine produce cutaneous vasoconstriction, they do so through different α-adrenergic mechanisms, with oxymetazoline primarily acting via α1 -adrenoceptors and brimonidine acting via α2 -adrenoceptors.

Anxiolytic effects of the GABAA receptor partial agonist, L-838,417: Impact of age, test context familiarity, and stress

The partial α2,3,5 GABAA receptor agonist, L-838,417 has been reported to have anxiolytic effects in adult rodents. Although maturational differences exist for the GABAA receptor subunits, the anxiolytic effects of L-838,417 have not been tested in younger animals. The goal of the present experiments was to determine whether L-838,417 reverses anxiety-like behavior induced by either an unfamiliar environment (Experiment 1) or repeated restraint stress (Experiment 2) differentially in adolescent and adult, male and female Sprague–Dawley rats using a modified social interaction test. In Experiment 1, rats were injected with 0, 0.5, 1.0, 2.0, or 4.0mg/kg L-838,417, i.p. and tested 30min later in an unfamiliar test context for 10min. In Experiment 2, rats were exposed to restraint stress (90min daily for 5days). Immediately after the last restraint session, animals were injected with L-838,417 and placed alone for 30min in the test apparatus to familiarize them to this context prior to the 10min social interaction test. In Experiment 1, L-838,417 produced anxiolytic effects in adults at 1.0mg/kg, as indexed by a transformation of social avoidance into preference and an increase in social investigation. In adolescents, a dose of 2.0mg/kg eliminated social avoidance, but had no anxiolytic effects on social investigation. Testing under familiar circumstances (Experiment 2) after repeated restraint stress eliminated age differences in sensitivity to L-838,417, with 0.5mg/kg reversing the anxiogenic effects of prior stress regardless of age, but with doses≥1 mg/kg decreasing social investigation, an effect possibly due in part to locomotor-impairing effects of this compound. Although locomotor activity was suppressed in both experiments, higher doses of L-838,417 were necessary to suppress locomotor activity in Experiment 1. Thus, anxiolytic effects of L-838,417 were found to be context-, age-, and stress-dependent.

The provision of analgesia and sedation in the PICU: current practice and recent advances

The provision of analgesia and sedation in the PICU: current practice and recent advances