A Bilayer Microneedle for Modulated Sequential Release of Adrenaline and Lidocaine for Prolonged Local Anesthesia.

Chronic pain emerges as a major global health issue, significantly impacting individuals' health and quality of life. In this study, we designed a bilayer microneedle loaded with lidocaine nanocomposites in the inner layer and adrenaline (Adr) in the outer layer (HCP MNs) for modulated sequential release to achieve prolonged local anesthesia. The obtained HCP MNs featured an intact structure with adequate mechanical strength for efficient skin penetration. The bilayer structure of MNs was evidenced by loading two fluorescent dyes in each layer. Furthermore, these HCP MNs were capable of inducing rapid as well as prolonged local anesthetic effects in guinea pigs. Hence, the bilayer MN coloaded with Adr and lidocaine nanocomposite serves as a promising transdermal delivery platform for chronic pain management.

Fushenmu treatment ameliorates RyR2 with related metabolites in a zebrafish model of barium chloride induced arrhythmia.

BACKGROUND: Fushenmu (Pini Radix in Poria, FSM) is a folk parasitic herb that has been mainly used for palpitation and amnesiain in traditional Chinese medicine (TCM). Recently, as an individual herb or a component of formulations, Fushenmu exhibits therapeutic potential for the treatment of cardiac arrhythmias. Yet, how specific targets or pathways of Fushenmu inhibit arrhythmia has not yet been reported. METHODS: Here, based on clinical functional genomics, metabolomics and molecular biologic technologies, a network construction strategy was adopted to identify FSM therapeutic targets and biomarkers that might explore its functions. RESULTS: In this study, it was found that FSM recovered arrhythmia-associated heart failure in barium chloride (BaCl2) induced arrhythmic zebrafish embryos, as was evidenced by the shortened cardiac sinus venosus-bulbus arteriosus (SV-BA) distance, smaller cardiovascular bleeding areas, and reduced cardiomyocyte apoptosis. Moreover, analysis via ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-QTOF-ESI-MS/MS) components identification and network pharmacology prediction showed that 11 main active components of FSM acted on 33 candidate therapeutic targets. Metabolomic analysis also suggested that FSM could rescue 242 abnormal metabolites from arrhythmic zebrafish embryos. Further analysis based on the combination of target prediction and metabolomic results illustrated that FSM down-regulated Ryanodine Receptor 2 (RyR2) expressions, inhibited adrenaline and 3',5'-Cyclic AMP (cAMP) levels in a dose-dependent manner, which was confirmed by metabolites quantification and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assay. CONCLUSION: In summary, this study revealed that FSM mitigated BaCl2 induced cardiac damage caused by arrhythmia by suppressing RyR2 expressions, decreasing adrenaline and cAMP through the adrenergic signalling pathway.

Mapping the primate thalamus: systematic approach to analyze the distribution of subcortical neuromodulatory afferents.

Neuromodulatory afferents to thalamic nuclei are key for information transmission and thus play critical roles in sensory, motor, and limbic processes. Over the course of the last decades, diverse attempts have been made to map and describe subcortical neuromodulatory afferents to the primate thalamus, including axons using acetylcholine, serotonin, dopamine, noradrenaline, adrenaline, and histamine. Our group has been actively involved in this endeavor. The published descriptions on neuromodulatory afferents to the primate thalamus have been made in different laboratories and are not fully comparable due to methodological divergences (for example, fixation procedures, planes of cutting, techniques used to detect the afferents, different criteria for identification of thalamic nuclei…). Such variation affects the results obtained. Therefore, systematic methodological and analytical approaches are much needed. The present article proposes reproducible methodological and terminological frameworks for primate thalamic mapping. We suggest the use of standard stereotaxic planes to produce and present maps of the primate thalamus, as well as the use of the Anglo-American school terminology (vs. the German school terminology) for identification of thalamic nuclei. Finally, a public repository of the data collected under agreed-on frameworks would be a useful tool for looking up and comparing data on the structure and connections of primate thalamic nuclei. Important and agreed-on efforts are required to create, manage, and fund a unified and homogeneous resource of data on the primate thalamus. Likewise, a firm commitment of the institutions to preserve experimental brain material is much needed because neuroscience work with non-human primates is becoming increasingly rare, making earlier material still more valuable.

Improving vasopressor use in cardiac arrest.

The Chain of Survival highlights the effectiveness of early recognition of cardiac arrest and call for help, early cardiopulmonary resuscitation and early defibrillation. Most patients, however, remain in cardiac arrest despite these interventions. Drug treatments, particularly the use of vasopressors, have been included in resuscitation algorithms since their inception. This narrative review describes the current evidence base for vasopressors and reports that adrenaline (1 mg) is highly effective at achieving return of spontaneous circulation (number needed to treat 4) but is less effective on long-term outcomes (survival to 30 days, number needed to treat 111) with uncertain effects on survival with a favourable neurological outcome. Randomised trials evaluating vasopressin, either as an alternative to or in addition to adrenaline, and high-dose adrenaline have failed to find evidence of improved long-term outcomes. There is a need for future trials to evaluate the interaction between steroids and vasopressin. Evidence for other vasopressors (e.g. noradrenaline, phenylephedrine) is insufficient to support or refute their use. The use of intravenous calcium chloride as a routine intervention in out of hospital cardiac arrest is not associated with benefit and may cause harm. The optimal route for vascular access between peripheral intravenous versus intraosseous routes is currently the subject of two large randomised trials. Intracardiac, endobronchial, and intramuscular routes are not recommended. Central venous administration should be limited to patients where an existing central venous catheter is in situ and patent.

Investigating the mechanism of antihypertensive actions of medicinal plants using some animal models

As the search for, and development of new drugs continues, drug companies engage in the large-scale pharmacological screening of medicinal plants. This creates the need to elucidate the mechanism of action of medicinal plants found to possess biological activity as a means of deriving their full therapeutic potential. This research was carried out to investigate the mechanism of the antihypertensive action of Vernonia amygdalina, Ocimum gratissimum, and Pterocarpus erinaceus using animal models. The dried 70% ethanolic extracts of the plants were prepared at varying concentrations ranging from 0.4 mg/mL to 50 mg/mL. These extracts were administered at varying doses alone and in the presence of selected antagonists like prazocin in anesthetized cat in-vivo and to rabbit jejunum and spontaneously beating guinea pig right atrium. Adrenaline and atropine were used as control drugs.The effects of these plants extracts were demonstrated on the Finkleman preparation and they were found to induce relaxation of the rabbit jejunum. They also reduced both the rate and force of contraction of spontaneously beating guinea pig's right atrium. The cardiovascular effects of the extracts were investigated on cat blood pressure. The effect of atropine tested in the presence of V. amygdalina and O. gratissimum showed a change in the pattern of induced fall in blood pressure but does block the fall in blood pressure induced by the extracts. While the exact mechanism of the antihypertensive action of these extracts has not been fully determined, the result of this research work proposes that the mechanism could either be blocking calcium channels or have direct activity on lowering blood pressure. It is therefore recommended that further studies be conducted on the extracts to better understand the mechanism of antihypertensive actions of these plants.

Paliperidone-Induced Acute Hyperglycemia Is Caused by Adrenaline Secretion via the Activation of Hypothalamic AMP-Activated Protein Kinase.

Although paliperidone-related hyperglycemia has been extensively examined, the underlying mechanisms have not yet been elucidated. We investigated the effects of a single intravenous injection of paliperidone (0.2, 0.4, or 0.6 mg/kg) on serum concentrations of glucose and other endogenous metabolites in rats. We also examined the effects of a single intravenous injection of paliperidone (0.4 mg/kg) on AMP-activated protein kinase (AMPK) activity in the hypothalamus and liver. To clarify the relationship between AMPK activity and adrenaline secretion, the effects of berberine, which inhibits hypothalamic AMPK, on paliperidone-induced hyperglycemia were assessed. Significant increases were observed in serum glucose, adrenaline, and insulin concentrations following intravenous injections of paliperidone at doses of 0.4 and 0.6 mg/kg. A propranolol pretreatment attenuated paliperidone-induced increases in serum concentrations of glucose, but not adrenaline. Significant increases were also noted in phosphorylated AMPK concentrations in the hypothalamus following the administration of paliperidone at a dose of 0.4 mg/kg. A berberine pretreatment attenuated paliperidone-induced increases in blood concentrations of glucose, adrenaline, and insulin and phosphorylated AMPK concentrations in the hypothalamus. Collectively, the present results demonstrated that an acute treatment with paliperidone induced hyperglycemia, which was associated with the effects of hypothalamic AMPK activation on the secretion of adrenaline.

Iatrogenic central retinal artery occlusion following retrobulbar anesthesia with adrenaline for vitreoretinal surgery: a case report.

BACKGROUND: We describe a patient presenting with central retinal artery occlusion (CRAO) of the right eye after retrobulbar anesthesia with adrenaline for macular pucker surgery. CASE PRESENTATION: The patient, a 67-year-old Caucasian man, developed a CRAO postoperatively by the next-day control likely due to the retrobulbar injection of a combination of Xylocaine and Bupivacaine with adrenaline as anesthetic. CONCLUSIONS: The addition of adrenaline to the standard anesthetic solution could be a risk factor for serious complications, such as CRAO.

Anti-Hypertensive Activity of Some Selected Unani Formulations: An Evidence-Based Approach for Verification of Traditional Unani Claims Using LC-MS/MS for the Evaluation of Clinically Relevant Blood Parameters in Laboratory Rats.

Background: Systemic arterial hypertension, which is associated with an increased risk of cardiovascular disease(CVD), is the most significant modifiable risk factor for mortality and morbidity worldwide. WHO has recognized Unanipathy as an alternate system of medicine. The aim of the present study is to investigate the anti-hypertensive activity of some selected unani formulations using L-NAME model. Method: Group I or hypertensive control group: L-NAME administered for 7 days and left for the next 7 days; Group II or KASgroup: L-NAME administered (i.p) for 7 days and L-NAME + KAS (1000 mg/kg b.w) for the next 7 days; Group III or DMM group: L-NAME administered (i.p) for 7 days and L-NAME + DMM (2000 mg/kg b.w) for the next 7 days; Group IV or MSR group: L-NAME administered (i.p) for 7 days and L-NAME + MSR (300 mg/kg b.w) for the next 7 days; Group V or HJ group: L-NAME administered (i.p) for 7 days and L-NAME + HJ (113 mg/kg b.w) for the next 7 days; Group VI or KGS group: L-NAME administered (i.p) for 7 days and L-NAME +KGS (2000 mg/kg b.w) for the next 7 days. Non-invasive systolic blood pressure and RR-interval (ECG) was measured. Plasma was investigated forsodium, potassium, nitrite, ANP, adrenaline, noradrenaline and aldosterone on day 0, 7 and 14 using LC-MS/MS. Result: Treatment showed a non-significant lowreduction in SBP (systolic blood pressure) of KAS, MSR and HJ while that of DMM was quite significant (p < 0.05), but in the case of KGS, SBP increased. DMM on day 14 significantly (p < 0.05) reduced plasma nitrite while no significant plasma Na+ was noted. In the case of both DMM and KGS, potassium increased significantly (p < 0.05) on day 14. No significant changes in plasma ANP and aldosterone was observed against DMM and KGS while blood levels of adrenaline and noradrenaline significantly (p < 0.05) changed. No significant change in body weight was found. Conclusions: L-NAME KAS, MSR and HJ showed no change in SBP while DMM showed a significant reduction in SBP with decreased plasma nitrite. Probably, DMM may have anti-hypertensive activity mediated through NO inhibition while KGS may involve central sympathomimetic action.

Cardioprotective Effect of Rumex vesicarius Linn. Leaf Extract against Catecholamine-Induced Cardiotoxicity.

Rumex vesicarius (L.) is a folklore medicinal herb that has been used for centuries to cure cardiovascular diseases. The present work was carefully designed to ascertain the pharmacological basis for R. vesicarius's therapeutic efficacy in cardiovascular diseases, as well as the underlying mechanism. In the ex vivo investigation, the aqueous-methanolic leaf extract of R. vesicarius was shown to have endothelium-dependent vasorelaxant effects in rabbit aorta tissue preparations, and its hypotensive responses were quantified by pressure and force transducers coupled to the Power Lab Data Acquisition System. Furthermore, when rabbits were subjected to adrenaline-induced myocardial infarction, R. vesicarius demonstrated cardioprotective characteristics. In contrast to the intoxicated group, the myocardial infarction model showed lower ALP, CK-MB, CRP, LDH, ALT, troponin, and AST levels (p > 0.005−0.000), as well as edema, necrosis, apoptosis, inflammatory cell enrolment, and necrosis. R. vesicarius exhibited significant antioxidant activity and delayed noradrenaline-induced platelet aggregation. Its cardioprotective, anticoagulant, and vasorelaxant properties in both investigations (in vivo and ex vivo) are mediated through partial endothelium-dependent, NO and calcium channel blockade mediated vasorelaxation. The minimizing of adrenaline, oxidative stress, and tissue damage demonstrate its therapeutic efficacy in cardiovascular diseases.

WALANT: Perceptions, approaches, and contraindications in a tertiary hand surgery unit.

Wide awake local anesthetic no tourniquet (WALANT) is gaining popularity amongst hand surgeons. Digital adrenaline use has been shown to be safe in multiple studies and the misconception forbidding it is receding. Phentolamine has been shown to safely reverse the effects of adrenaline should the feared complication of digital ischemia occur. A survey was circulated to 40 specialist practitioners who regularly perform hand procedures at a major tertiary plastic and hand surgery unit. Knowledge and understanding of WALANT, onset and duration of adrenaline effects and reversal was assessed. Whilst the majority of respondents (80%) recognized digital adrenaline use as safe, only 65% were aware of the delay until adrenaline takes full effect. Similarly, only 25% of respondents were aware of the duration of effect of adrenaline. Half of respondents were aware that phentolamine is the established reversal agent for adrenaline with only 20% knowing the correct dose. Given the lack of clinician knowledge surrounding adrenaline and its reversal, we feel that to safely undertake WALANT surgery at our Unit a WALANT protocol must be implemented. Drawing on the successes in the airline industry, a variety of safety frameworks have been established to deliver targeted education for prevention and eventual management of predictable risks. We plan to develop a checklist style protocol targeting the knowledge gaps raised in the survey. This will educate and equip all practitioners working with adrenaline with the knowledge to safely manage complications should they occur. LEVEL OF EVIDENCE: Level 5 (UK Oxford Centre for Evidence based Medicine (CEBM) Levels of Evidence).

Study of cardioprotective activity of the methanolic extract of the aerial parts of Bauhinia madagascariensis compared to Bauhinia purpurea against adrenaline-induced myocardial toxicity in rats.

Cardiovascular ailments result in a great rate of mortality all over the world. Myocardial infarction is a common presentation of cardiovascular disease. The current work aimed to investigate and compare the cardioprotective potentials of methanolic extracts from the aerial parts from Bauhinia purpurea and Bauhinia madagascariensis in adrenaline-induced cardiotoxicity in rats. The rats were categorized into five groups as follows: control group, adrenaline-treated group, Bauhinia purpurea extract + adrenaline treated group, Bauhinia madagascariensis+ adrenaline treated group, reference drug (captopril) + adrenaline treated group. The extracts as well as the reference drug were orally administered for 21 consecutive days. On day 22, adrenaline was injected as a single dose for 2 consecutive days. The adrenaline injection caused a significant increase (p < 0.05) in serum cardiac markers (ALT, AST, CK-MB, LDH), angiotensin-converting enzyme (ACE) and matrix metalloproteinase (MMP-9), inducible nitric oxide synthase (iNOS) activities, tumor necrosis factor-α (TNF-α) cardiac lipid peroxides (MDA) levels and a significant decline (p < 0.05) in cardiac reduced glutathione (GSH) levels compared to their corresponding controls. The pretreatment extracts significantly ameliorated (p < 0.05) these alterations. Histopathological investigations supported the biochemical data. Bauhinia madagascariensis extract exerted a significant anti-inflammatory activity than that of Bauhinia purpurea. In addition, Bauhinia madagascariensis extract revealed a significant inhibitory activity on ACE compared to that of Bauhinia purpurea, (p < 0.05). These data reveal that both extracts had a strong protective activity against adrenaline-induced cardiotoxicity via improving cardiac function, reducing ECG and histopathological changes that could be mediated in part through its anti-oxidant, anti-inflammatory effects, inhibition of ACE, MMP-9, and iNOS.

Circulating microRNAs predispose to takotsubo syndrome following high-dose adrenaline exposure.

AIMS: Takotsubo syndrome (TTS) is an acute heart failure, typically triggered by high adrenaline during physical or emotional stress. It is distinguished from myocardial infarction (MI) by a characteristic pattern of ventricular basal hypercontractility with hypokinesis of apical segments, and in the absence of culprit coronary occlusion. We aimed to understand whether recently discovered circulating biomarkers miR-16 and miR-26a, which differentiate TTS from MI at presentation, were mechanistically involved in the pathophysiology of TTS. METHODS AND RESULTS: miR-16 and miR-26a were co-overexpressed in rats with AAV and TTS induced with an adrenaline bolus. Untreated isolated rat cardiomyocytes were transfected with pre-/anti-miRs and functionally assessed. Ventricular basal hypercontraction and apical depression were accentuated in miR-transfected animals after induction of TTS. In vitro miR-16 and/or miR-26a overexpression in isolated apical (but not basal), cardiomyocytes produced strong depression of contraction, with loss of adrenaline sensitivity. They also enhanced the initial positive inotropic effect of adrenaline in basal cells. Decreased contractility after TTS-miRs was reproduced in non-failing human apical cardiomyocytes. Bioinformatic profiling of miR targets, followed by expression assays and functional experiments, identified reductions of CACNB1 (L-type calcium channel Cavß subunit), RGS4 (regulator of G-protein signalling 4), and G-protein subunit Gß (GNB1) as underlying these effects. CONCLUSION: miR-16 and miR-26a sensitize the heart to TTS-like changes produced by adrenaline. Since these miRs have been associated with anxiety and depression, they could provide a mechanism whereby priming of the heart by previous stress causes an increased likelihood of TTS in the future.

Effect of Phytopreparations Based on Bioreactor-Grown Cell Biomass of Dioscorea deltoidea, Tribulus terrestris and Panax japonicus on Carbohydrate and Lipid Metabolism in Type 2 Diabetes Mellitus.

In the present study, we explored the therapeutic potential of bioreactor-grown cell cultures of the medicinal plant species Dioscorea deltoidea, Tribulus terrestris and Panax japonicus to treat carbohydrate metabolism disorders (CMDs) in laboratory rats. In the adrenaline model of hyperglycemia, aqueous suspensions of cell biomass pre-administered at a dose of 100 mg dry biomass/kg significantly reduced glucose level in animal blood 1-2.5 h (D. deltoidea and T. terrestris) or 1 h (P. japonicus) after adrenaline hydrochloride administration. In a streptozotocin-induced model of type 2 diabetes mellitus, the cell biomass of D. deltoidea and T. terrestris acted towards normalization of carbohydrate and lipid metabolism, as evidenced by a significant reduction of daily diuresis (by 39-57%), blood-glucose level (by 46-51%), blood content in urine (by 78-80%) and total cholesterol (25-36%) compared to animals without treatment. Bioactive secondary metabolites identified in the cell cultures and potentially responsible for their actions were deltoside, 25(S)-protodioscin and protodioscin in D. deltoidea; furostanol-type steroidal glycosides and quinic acid derivatives in T. terrestris; and ginsenosides and malonyl-ginsenosides in P. japonicus. These results evidenced for high potential of bioreactor-grown cell suspensions of these species for prevention and treatment of CMD, which requires further investigation.

Jasminum sambac: A Potential Candidate for Drug Development to Cure Cardiovascular Ailments.

Jasminum sambac (L.) is a South Asian folkloric medicinal plant that has traditionally been used to treat cardiovascular problems. The current investigation was meticulously organized to explore the pharmacological foundation for the medicinal uses of J. sambac pertaining to cardiovascular ailments and to investigate the core mechanisms. Mechanistic investigation revealed that crude leaf extract of J. sambac produced ex-vivo vasorelaxant effects in endotheliumintact aorta ring preparation and hypotensive effect was recorded via pressure and force transducers coupled to the Power Lab Data Acquisition System. Moreover; J. sambac showed cardioprotective effects against adrenaline -induced left ventricular hypertrophy in rabbits observed hemodynamic. CK-MB, LDH, troponin, CRP, ALT, AST, ALP levels were shown to be lower in the myocardial infarction model, as were necrosis, oedema, and inflammatory cell recruitment in comparison to control. J. sambac has shown good antioxidant potential as well as prolonged the noradrenaline induced platelet adhesion. The vasorelaxant and cardioprotective effects in both in vivo and ex vivo experiments, which are enabled by activation of muscarinic receptor and/or releasing the nitric oxide and by reducing the adrenaline, induced oxidative stress, justifying its usage in cardiovascular disorders.

WALANT Protocol: Stop before you block.

The use of Wide Awake Local Anaesthetic No Tourniquet (WALANT) amongst Plastic and Orthopaedic Hand Surgeons has been accelerated by the impact of the COVID-19 pandemic and associated risks of general anaesthesia. Benefits of WALANT include a bloodless field, improved recovery, on-table testing, as well as cost and time savings. Whilst more clinical trials are underway to fully elucidate safety-profile and outcomes, there is a lack of consensus and clarity over contraindications to WALANT. A survey of trainees identified that only one-in-five were aware of the appropriate reversal agent in the event of inadequate perfusion. We feel that a WALANT checklist should be developed and implemented for use immediately prior to administration of local anaesthetic with adrenaline to an extremity, building on the successes of the World Health Organisation (WHO) and the Royal College of Anaesthetists checklists. Such a checklist should include contraindications to WALANT and make the operator aware of the availability, dose and location of Phentolamine as a reversal agent. Introducing this checklist will help to facilitate safer and more effective use of WALANT within Hand Surgery.

Microporous P-doped carbon spheres sensory electrode for voltammetry and amperometry adrenaline screening in human fluids.

An electrochemical sensor-based phosphorus-doped microporous carbon spheroidal structures (P-MCSs) has been designed for selective adrenaline (ADR) signaling in human blood serum. The P-MCS electrode sensor is built with heterogeneous surface alignments including multiple porous sizes with open holes and meso-/macro-grooves, rough surface curvatures, and integral morphology with interconnected and conjugated microspheres. In addition, the P atom-doped graphitic carbon forms highly active centers, increases charge mobility on the electrode surface, creates abundant active centers with facile functionalization, and induces binding to ADR molecules. The designed P-MCS electrode exhibits ultrasensitive monitoring of ADR with a low detection limit of 0.002 µM and high sensitivity of 4330 µA µM-1 cm-2. In addition, two electrochemical techniques, namely, square wave voltammetry (SWV) and chronoamperometry (CA), were used; these techniques achieve high stability, fast response, and a wide linear range from 0.01 to 6 µM. The sensing assays based on P-MCSs provide evidence of the formation of active interfacial surface-to-ADR binding sites, high electron diffusion, and heavy target loads along with/without a plane of spheroids. Thus, P-MCSs can be used for the routine monitoring of ADR in human blood serum, providing a fast response, and requiring highly economical materials at extremely low concentrations. Electrode surface modulation based on P-doped carbon spheres (P-MCS) exhibits high electrochemical activity with fast charge transport, multi-diffusible active centers, high loading of ADR, and facile molecular/electron diffusion at its surface. The P-MCS sensitively and selectively detects the ADR in human fluids and can be used for clinical investigation of some neuronal diseases such as Alzheimer diseases.

Applying the WALANT technique to surgical treatment of distal radius fractures.

The Wide-Awake Local Anesthesia No Tourniquet (WALANT) method is a recent anesthesia option for surgery of the upper limbs based on the injection of an anesthetic solution containing adrenaline at the surgical site, hence circumventing tourniquet use. In a prospective study, we compared the functional outcomes using this anesthesia technique with those of the regional anesthesia (RA) technique for the surgical care of distal radius fractures (DRF). From November 2019 to June 2020, a non-randomized, single-center study was conducted with a cohort of 41 patients suffering from a DRF and who received volar plate fixation at a university hospital center. Twenty-one patients had WALANT surgery and 20 had RA with installation of a tourniquet. Over a period of 7 months, the clinical and radiological outcomes as well as the QuickDASH functional score were evaluated. Recovery of wrist function return to work, and analgesic withdrawal for the WALANT group occurred earlier than for the RA group. No noticeable differences were found regarding surgery duration or radiographic results. Using WALANT, functional wrist recovery occurs earlier than with RA. In our study, earlier analgesic stoppage, a quicker return to work and resumption of activity were observed with WALANT. As such, it should become part of the therapeutic arsenal for surgical treatment of DRF.

Pharmacological Justification for the Medicinal Use of Plumeria rubra Linn. in Cardiovascular Disorders.

Plumeria rubra (L.) is a traditional folkloric medicinal herb used to treat cardiovascular disorders. The present investigation was methodically planned to investigate the pharmacological foundations for the therapeutic effectiveness of P. rubra in cardiovascular illnesses and its underlying mechanisms. Ex vivo vaso-relaxant effects of crude leaf extract of P. rubra were observed in rabbit aorta ring preparations. Hypotensive effects were measured using pressure and force transducers connected to the Power Lab data acquisition system. Furthermore, P. rubra displayed cardioprotective properties in rabbits when they were exposed to adrenaline-induced myocardial infarction. In comparison to the intoxicated group, the myocardial infarction model showed decreased troponin levels, CK-MB, LDH, ALT, ALP, AST, and CRP, as well as necrosis, apoptosis, oedema, and inflammatory cell enrollment. P. rubra has revealed good antioxidant properties and prolonged the noradrenaline intoxicated platelet adhesion. Its anticoagulant, vasorelaxant, and cardioprotective effects in both in vivo and ex vivo investigations are enabled by blocking L-type calcium channels, lowering adrenaline, induced oxidative stress, and tissue tear, justifying its therapeutic utility in cardiovascular disorders.

An Advanced Statistical Approach Using Weighted Linear Regression in Electroanalytical Method Development for Epinephrine, Uric Acid and Ascorbic Acid Determination.

In this study, the use of weighted linear regression in the development of electrochemical methods for the determination of epinephrine (EP), ascorbic acid (AA), and uric acid (UA) is presented. The measurements were performed using a glassy carbon electrode and square-wave voltammetry (SWV). All electroanalytical methods were validated by determination of the limit of detection, limit of quantification, linear concentration range, accuracy, and precision. The normal distribution of all data sets was checked using the quantile-quantile plot and Kolmogorov-Smirnov statistical tests. The heteroscedasticity of the data was tested using Hartley's test, Bartlett's test, Cochran's C test, and the analysis of residuals. The heteroscedastic behavior was observed with all analytes, justifying the use of weighted linear regression. Six different weighting factors were tested, and the best weighted model was determined using relative percentage error. Such statistical approach improved the regression models by giving greater weight on the values with the smallest error and vice versa. Consequently, accuracy of the analytical results (especially in the lower concentration range) was improved. All methods were successfully used for the determination of these analytes in real samples: EP in an epinephrine auto-injector, AA in a dietary supplement, and UA in human urine. The accuracy and precision of real sample analysis using best weighted model gave satisfactory results with recoveries between 95.21-113.23% and relative standard deviations between 0.85-7.98%. The SWV measurement takes about 40 s, which makes the presented methods for the determination of EP, AA, and UA a promising alternative to chromatographic techniques in terms of speed, analysis, and equipment costs, as the analysis is performed without organic solvents.

Wide-awake local anaesthesia no tourniquet (WALANT) vs regional or general anaesthesia for flexor tendon repair in adults: protocol for a systematic review and meta-analysis.

BACKGROUND: Flexor tendon injuries most commonly occur following a penetrating injury to the hand or wrist. These are challenging injuries and the standard treatment is surgical repair under general or regional anaesthesia. 'Wide-awake' surgery is an emerging technique in hand surgery where a conscious patient is operated on under local anaesthetic. The vasoconstrictive effect of adrenaline (epinephrine) creates a 'bloodless' operating field and a tourniquet is not required. The potential advantages include intra-operative testing of the repair; removal of the risks of general anaesthesia; reduced costs; no aerosol generation from intubation therefore reduced risk of COVID-19 spread to healthcare professionals. The aim of this study will be to systematically evaluate the evidence to determine if wide-awake surgery is superior to general/regional anaesthetic in adults who undergo flexor tendon repair. METHODS: We designed and registered a study protocol for a systematic review and meta-analysis of comparative and non-comparative studies. The primary outcome will be functional active range of motion. Secondary outcomes will be complications, resource use (operative time) and patient-reported outcome measures. A comprehensive literature search will be conducted (from 1946 to present) in MEDLINE, EMBASE, CINAHL, and Cochrane Library. Grey literature will be identified through Open Grey, dissertation databases and clinical trials registers. All studies on wide-awake surgery for flexor tendon repair will be included. The comparator will be general or regional anaesthesia. No limitations will be imposed on peer review status or language of publication. Two investigators will independently screen all citations, full-text articles and abstract data. Potential conflicts will be resolved through discussion or referral to a third author when necessary. The study methodological quality (or bias) will be appraised using an appropriate tool. If feasible, we will conduct a random effects meta-analysis. DISCUSSION: This systematic review will summarise the best available evidence and definitively establish if function, complications, cost, or patient-reported outcomes are improved when flexor tendons are repaired using wide-awake technique. It will determine if this novel approach is superior to general or regional anaesthesia. This knowledge will help guide hand surgeons by continuing to improve outcomes from flexor tendon injuries. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020182196.