Alpha 2-adrenergic Receptor Agonist Research Articles

The alpha2-adrenergic receptor agonist clonidine protects against cerebral ischemia/reperfusion induced neuronal apoptosis in rats.

Apoptosis is the crucial pathological mechanism following cerebral ischemic injury. Our previous studies demonstrated that clonidine, one agonist of alpha2-adrenergic receptor (α2-AR), could attenuate cerebral ischemic injury in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). However, it's unclear whether clonidine exerts neuroprotective effects by regulating neuronal apoptosis. In this study, we elucidated whether clonidine can exert anti-apoptotic effects in cerebral ischemic injury, and further explored the possible mechanisms. Neurological deficit score was measured to evaluate the neurological function. TTC staining was used for the measurement of brain infarct size. Hematoxylin-Eosin (HE) staining was applied to examine the cell morphology. TUNEL and DAPI fluorescent staining methods were used to analyze the cell apoptosis in brain tissue. Fluorescence quantitative real-time PCR was performed to assess the gene expression of Caspase-3 and P53. Western blotting assay was applied to detect the protein expression of Caspase-3 and P53. The results showed that clonidine improved neurological function, reduced brain infarct size, alleviated neuronal damage, and reduced the ratio of cell apoptosis in the brain with MCAO/R injury. moreover, clonidine down-regulated the gene and protein expression of Caspase-3 and P53 which were over-expressed after MCAO/R injury. Whereas, yohimbine (one selective α2-AR antagonist) mitigated the anti-apoptosis effects of clonidine, accompanied by reversed gene and protein expression changes. The results indicated that clonidine attenuated cerebral MCAO/R injury via suppressing neuronal apoptosis, which may be mediated, at least in part, by activating α2-AR.

Clinical features and treatment of rosacea

Background: Rosacea is a common facial dermatological disease characterized by central erythema and flushing. It is more common in females than males, with a prevalence of approximately 5.5% in the global population and 2.4% among all dermatological outpatients. In 2002, the National Rosacea Society Expert Committee suggested a subtype-based standardized classification system. The most common subtype of rosacea is erythematotelangiectatic rosacea (ETR), followed by papulopustular rosacea (PPR), phymatous rosacea, and ocular rosacea.Current Concepts: Rosacea is characterized by hyperactive innate and neurovascular immune reactions, which lead to altered adaptive immune reactions and hyperreactive inflammation. In 2017, the National Rosacea Society Expert Committee developed a phenotype-based classification system. The diagnostic features include persistent centrofacial erythema and phymatous changes. ETR is associated with sensitive skin and may have a debilitating psychological impact, often leading to psychological conditions such as depression and anxiety. Doxycycline and minocycline are considered the gold-standard oral treatments for rosacea. Topical ivermectin and metronidazole are commonly used to treat PPR. Low-dose isotretinoin is an alternative to avoid long-term chronic antibiotic use. Carvedilol and propranolol are off-label medications used to reduce persistent facial flushing and erythema in rosacea. Some alpha-adrenergic receptor agonists have also been approved for the treatment of persistent erythema in rosacea.Discussion and Conclusion: Rosacea exhibits multiple phenotypic manifestations. The treatment approach is individualized for each patient through the customization of multimodal treatments, including the avoidance of trigger factors and the assessment of comorbid diseases.

A confirmed case of xylazine-induced skin ulcers in a person who injects drugs in Miami, Florida, USA

BackgroundXylazine is an alpha-2 adrenergic receptor agonist that has emerged as a contaminant in the illicit drug supply of fentanyl. Xylazine use may be suspected in naloxone-resistant overdoses and atypical, chronic wounds in people who use drugs (PWUD). This case is unique because it is the first case to our knowledge describing wound care for a xylazine-induced wound with a confirmatory xylazine test strip (XTS) in the setting of a syringe services program (SSP) and in the state of Florida.Case presentationA 43-year-old woman with a past medical history of severe opioid use disorder and stimulant use disorder presented to a student-run clinic at a Miami SSP for wound care. She had multiple ulcerations diffusely over her bilateral forearms with surrounding erythema and warmth. Seven weeks later, she presented to clinic again for wound care because her wounds had progressed. At this visit, a XTS was used to confirm the presence of xylazine in her urine. Wound care management and harm reduction strategies employed at both visits were informed by best clinical judgement due to lack of formal guidelines at the time. Wound outcomes are unknown as the patient has not returned to clinic.ConclusionsMany PWUD at highest risk for acute and chronic health consequences of xylazine-adulterated fentanyl do not have access to healthcare outside of low barrier clinics and SSPs due to lack of insurance or mistrust of the traditional healthcare system due to stigma. There is an urgent need for access to XTS for PWUD and clinical practice guidelines for the treatment of xylazine-related wounds in outpatient clinics.

Serotonergic and Adrenergic Neuroreceptor Manipulation Ameliorates Core Symptoms of ADHD through Modulating Dopaminergic Receptors in Spontaneously Hypertensive Rats.

The core symptoms of attention deficit hyperactivity disorder (ADHD) are due to the hypofunction of the brain's adrenergic (NE) and dopamine (DA) systems. Drugs that enhance DA and NE neurotransmission in the brain by blocking their transporters or receptors are the current therapeutic strategies. Of late, the emerging results point out the serotonergic (5-HT) system, which indirectly modulates the DA activity in reducing the core symptoms of ADHD. On this basis, second-generation antipsychotics, which utilize 5-HT receptors, were prescribed to children with ADHD. However, it is not clear how serotonergic receptors modulate the DA activity to minimize the symptoms of ADHD. The present study investigates the efficacy of serotonergic and alpha-2 adrenergic receptor manipulation in tackling the core symptoms of ADHD and how it affects the DA neuroreceptors in the brain regions involved in ADHD. Fifteen-day-old male spontaneously hypertensive rats (SHRs) received 5-HT1A agonist (ipsapirone) or 5-HT2A antagonist (MDL 100907) (i.p.) or alpha-2 agonist (GFC) from postnatal days 15 to 42 along with age-matched Wistar Kyoto rats (WKY) (n = 8 in each group). ADHD-like behaviors were assessed using a battery of behavioral tests during postnatal days 44 to 65. After the behavioral tests, rat brains were processed to estimate the density of 5-HT1A, 5-HT2A, DA-D1, and DA-D2 neuroreceptors in the prefrontal cortex, the striatum, and the substantia nigra. All three neuroreceptor manipulations were able to minimize the core symptoms of ADHD in SHRs. The positive effect was mainly associated with the upregulation of 5-HT2A receptors in all three areas investigated, while 5-HT1A was in the prefrontal cortex and the substantia nigra. Further, the DA-D1 receptor expression was downregulated by all three neuroreceptor manipulations except for alpha-2 adrenergic receptor agonists in the striatum and 5-HT2A antagonists in the substantia nigra. The DA-D2 expression was upregulated in the striatum while downregulated in the prefrontal cortex and the substantia nigra. In this animal model study, the 5-HT1A agonist or 5-HT2A antagonist monotherapies were able to curtail the ADHD symptoms by differential expression of DA receptors in different regions of the brain.

Combination of a propofol emulsion with alpha-2 adrenergic receptor agonists used for multimodal analgesia or sedation in intensive care units: a physicochemical stability study

ObjectivesTo assess the physicochemical stability of the combination of a propofol emulsion with an alpha-2 (α2) adrenergic receptor agonist (α2A; clonidine or dexmedetomidine) under conditions mimicking routine practice in an...

Intranasal alpha-adrenergic receptor agonists and corticosteroids as medical treatments for nasal congestion

Nasal congestion has been a longstanding issue which exerts burdens on both individual patients and society as a whole. It arises from various underlying illnesses like nasal polyposis, rhinosinusitis, allergic rhinitis and rhinitis medicamentosa, but the fundamental mechanism of induced nasal congestion is nasal mucosas swelling as a result of inflammation in all of these cases. Among all the therapies currently available, intranasal sprays of alpha-adrenergic receptor agonists or corticosteroids appeared to be prominent options. After reviewing research on treatments extensively, limited studies focused on the comparison of -adrenergic agonists and corticosteroids. This research explores the mechanisms, efficacy, and safety of these two medical approaches. Intranasal alpha-adrenergic receptor agonist sprays target the smooth muscles for vasoconstriction, acting rapidly to give way to airflow. They are effective as a treatment for short-term nasal congestion, otherwise, continued use may lead to rhinitis medicamentosa. Corticosteroid sprays, on the other hand, aim to reduce the severity of nasal inflammation via suppression of pro-inflammatory molecules. They are a promising treatment barely with concerns about the occurrence of side effects, authenticated by their excellent pharmaceutical performance over years.

Evaluation of The Effects of Dexmedetomidine against Carbontetracloride-Induced Nephrotoxicity via Oxidative Stress and Apoptosis

Objective: The objective of this work is to investigate the histological and biochemical consequences of administering Dexmedetomidine (DEX), an alpha-2 adrenergic receptor agonist with notable sedative qualities as well as antioxidant and anti-inflammatory characteristics, in the context of Carbon tetrachloride (CCl4)-induced kidney injury. Materials and Methods: The experimental design involved the random allocation of 30 Sprague-Dawley rats into three distinct groups. The experimental group designated as Group 1 received a single intraperitoneal administration of 1ml of saline solution containing 0.09% NaCl. Group 2 received an intraperitoneal injection of carbon tetrachloride (CCl4) at a dosage of 2 milliliters per kilogram. Group 3, referred to as the CCl4+Dexmedetomidine group, received a solitary intraperitoneal (i.p.) dosage of 100 µg/kg dexmedetomidine one hour before the intraperitoneal administration of 2mL/kg CCl4. Results: Extensive necrosis and debris accumulation were observed in the tubules, particularly in the proximal tubules, within the CCl4-applied group. An elevation in malondialdehyde (MDA) concentrations and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) positivity, along with a reduction in glutathione (GSH) levels, was found in the renal tissues of the CCl4 experimental group as compared to the control group. In contrast, the CCl4+DEX group exhibited a reduction in the quantity of necrotic tubular cells, levels of MDA, and TUNEL positive. Additionally, there was an elevation in GSH levels compared to the group treated with CCl4 alone. Conclusions: The administration of dexmedetomidine has been observed to potentially provide a protective effect against renal damage induced by CCl4. This phenomenon could potentially be linked to the modulation of tissue oxidative stress markers and the attenuation of apoptotic rate. The findings of our investigation provide evidence in favour of the utilization of dexmedetomidine as a promising therapeutic drug for mitigating renal injury.

Hepatorenal syndrome: Updates.

Hepatorenal syndrome: Updates.

Допоміжні засоби фармакологічної терапії при гострих отруєннях фосфорорганічими сполуками антихолінестеразної дії (огляд літератури)

The current standards of treatment the acute OPC poisoning with anticholinesterase action remain insufficient, despite the significant number of researches in this area conducted in the world. One of the ways to solve this problem is to use a wider range of pathogenetically determined pharmacologic agents. The Aim of the Research. To observe and summarize the published results of investigation the pharmacological therapeutic appliance for acute OPC poisoning at the stages of preclinical and early clinical evaluation. Methods. System content analysis of literature data using the PubMed and Google Scholar databases. Results and Conclusions. The investigation of pharmacological therapeutic appliance effectiveness for acute anticholinesterase OPC poisoning remains relevant when taking into account the complexity of the intoxication pathogenesis. The main lines of pharmacological agents’ research for the acute anticholinesterase OPC poisoning include the study of n-cholinoreceptor antagonists, benzodiazepine receptor agonists, NMDA-receptor antagonists, H1-histamine receptor antagonists, alpha-adrenergic receptor agonists, enzymatic antidote, antioxidants, agonists of beta-adrenergic blockers, and also magnesium sulfate, sodium bicarbonate, lipid emulsions. The investigations of clinically available therapeutic appliance continue both in animal experiments and at the clinical application stage. Such investigations are also important given the need for poisoning emergency care under conditions when specific therapies are missing or limited. Keywords: organophosphorus compounds, acute poisoning, therapeutic appliance.

The New Stealth Drug on the Street: A Narrative Review of Xylazine as a Street Drug.

Xylazine is an alpha-adrenergic receptor agonist approved for use only in animals with a prescription from a veterinarian. It is a powerful sedative that is slowly infiltrating the recreational street drug scene and is often used by polysubstance abusers. Known as "tranq," it can be fatal, and xylazine-induced toxicity cannot be reversed with naloxone or nalmefene. Due to its vasoconstrictive effects, chronic use of xylazine is associated with necrotic skin lesions and general deterioration of health. Since xylazine is not approved for human use and is not scheduled as a controlled substance, there are no human studies to provide evidence of drug-drug interactions, lethal doses, or reversal protocols. Xylazine is available online without a prescription. Street drug users may take xylazine knowingly or unknowingly, as it is often combined with other illicit substances such as fentanyl. There are no rapid tests for xylazine, although there are specialty tests that can be ordered. Xylazine represents a major threat to street drug users and another challenge to emergency healthcare workers, first responders, and others who care for those who have taken this "new" street drug.

Vagal nerve activity and sympathetic nerve activity are suppressed by alpha-2 adrenergic receptor agonists in conscious rats

Vagal nerve activity (VNA) and sympathetic nerve activity (SNA) have been known to influence each other and changes in their activity directly, but details on this remain unknown. This study used an alpha-2 adrenergic receptor agonist (dexmedetomidine) to study how SNA affects VNA in the conscious state. Electroencephalography, electromyography, electrocardiography, cervical VNA, renal SNA, and catheters for arterial pressure measurement and intravenous drug administration were measured after male Wistar rats were anesthetized and implanted with electrodes. Dexmedetomidine (50 micro g/kg) was intravenously administered in conscious rats. Cervical VNA decreased and reached its lowest values about 10 min after intravenous dexmedetomidine administration. However, renal SNA, electromyography, and heart rate decreased immediately after administration, whereas arterial pressure increased immediately. These results show that alpha-2 adrenergic receptor agonists simultaneously inhibit VNA and SNA. Furthermore, the present data suggest that excessive SNA activation increases norepinephrine release, inducing an increase in the concentration of circulating norepinephrine, which in turn inhibits SNA via negative feedback and suppresses VNA. JST (JPMJMS2023) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Number Needed to Treat and Number Needed to Harm From Two Phase 3 Studies of Sublingual Dexmedetomidine for Treating Acute Agitation in Patients With Schizophrenia and Bipolar Disorder

AbstractBackgroundEpisodes of acute agitation can occur in individuals who suffer from schizophrenia or bipolar disorder and these can be a significant challenge for patients and for those who provide care to them. Sublingual dexmedetomidine is a selective alpha2-adrenergic receptor agonist that was recently approved by the US Food and Drug Administration for the treatment of agitation in adults with schizophrenia or bipolar disorder. The sublingual form of dexmedetomidine does not undergo first-pass hepatic metabolism, thus resulting in greater absorption than when ingested. In two Phase 3 studies of adults with schizophrenia or bipolar disorder, sublingual dexmedetomidine significantly reduced acute agitation at 2 hours, as measured by the five-item Positive and Negative Syndrome Scale-Excited Component (PEC). When initially appraising the potential utility of a new medication, number needed to treat (NNT) and needed to harm (NNH) can be helpful to assess the size of the treatment effect and, hence, clinical relevance.ObjectiveCalculation of NNT and NNH through post hoc analysis of Phase 3 data.MethodsPost hoc analysis of data were performed on data from two double-blind, randomized, placebo-controlled studies of sublingual dexmedetomidine in adults with schizophrenia or bipolar disorder experiencing acute agitation. Patients were randomized to a single dose of sublingual dexmedetomidine 180 μg, 120 μg, or placebo. The primary endpoint was mean change from baseline in the PEC total score. A therapeutic response was defined as a ≥40% reduction from baseline in PEC total score at 2 hours. NNT was calculated for PEC response rate for sublingual dexmedetomidine versus placebo. NNH was calculated using the incidence of adverse events for sublingual dexmedetomidine versus placebo. Likelihood to be helped or harmed (LHH) was calculated as the ratio of NNH to NNT.ResultsNNT (95% CI) was 3 (2, 3) for 180 mcg and 3 (3, 4) for 120 ug in patients with schizophrenia and 3 (2, 3) for 180 mcg and 4 (3, 6) for 120 ug in patients with bipolar disorder. NNH was greater than 10 for all AEs except somnolence, where NNH was 7 (5, 10) for all doses pooled from both studies. LLH values were greater than 1 for efficacy versus applicable tolerability outcomes in all cases.ConclusionsThis post hoc analysis demonstrated favorable NNT and NNH values for sublingual dexmedetomidine. In all instances therapeutic response was encountered more frequently than any adverse event. These values compare favorably to similar analyses for other approved agents for the treatment of agitation associated with schizophrenia or bipolar disorder, including intramuscular and inhaled formulations.FundingBioXcel Therapeutics, Inc.

Dexmedetomidine: An Alternative to Pain Treatment in Neonatology.

Infants might be exposed to pain during their admissions in the neonatal intensive care unit [NICU], both from their underlying conditions and several invasive procedures required during their stay. Considering the particularities of this population, recognition and adequate management of pain continues to be a challenge for neonatologists and investigators. Diverse therapies are available for treatment, including non-pharmacological pain management measures and pharmacological agents (sucrose, opioids, midazolam, acetaminophen, topical agents…) and research continues. In recent years one of the most promising drugs for analgesia has been dexmedetomidine, an alpha-2 adrenergic receptor agonist. It has shown a promising efficacy and safety profile as it produces anxiolysis, sedation and analgesia without respiratory depression. Moreover, studies have shown a neuroprotective role in animal models which could be beneficial to neonatal population, especially in preterm newborns. Side effects of this therapy are mainly cardiovascular, but in most studies published, those were not severe and did not require specific therapeutic measures for their resolution. The main objective of this article is to summarize the existing literature on neonatal pain management strategies available and review the efficacy of dexmedetomidine as a new therapy with increasing use in the NICU.

Emergency Palliative Cancer Care: Dexmedetomidine Treatment Experiences-A Retrospective Brief Report on Nine Consecutive Cases.

Dexmedetomidine, an alpha-2 adrenergic receptor agonist with potential opioid sparing properties, is utilized in palliative medicine, but the knowledge base for this practice is limited. We describe concomitant use of dexmedetomidine and opioids in an acute palliative care unit. We included all hospitalized palliative cancer care patients treated with dexmedetomidine from January 2019 to January 2021. Demographics, opioid doses, dexmedetomidine indications and dosing, reported effects and adverse responses, as well as treatment lengths were recorded. Three women and six men aged 42-66years with metastatic cancer and Eastern Cooperative Oncology Group (ECOG) performance status I-IV used dexmedetomidine and opioids concomitantly. Indications for dexmedetomidine were pain (n = 7) and anxiety (n = 2). Dexmedetomidine was administered intravenously in two patients and subcutaneously in seven. All administrations were continuous infusions; initial doses ranged from 240 to 1344µg/24h with later doses from 240 to 2440µg/24h. Physicians reported relief from pain and anxiety, but two patients required neuraxial pain management during admission. At day 2 of dexmedetomidine treatment, the opioid dose was reduced in six out of nine patients. For all patients with available data at day 7, mean opioid dose was reduced to 74% of the initial dose. When excluding the two patients requiring neuraxial pain management, the corresponding number was 80%. Two patients had transient hypotension, but dexmedetomidine was well tolerated and in no cases withdrawn due to adverse effects. Mean dexmedetomidine treatment length was 40days. Dexmedetomidine treatment decreased opioid consumption and was well tolerated in a retrospective study of nine palliative cancer care patients. It may represent a treatment option late in the disease trajectory.

Use of Dexmedetomidine in a Patient Allergic to Clonidine Presenting for an Awake Craniotomy: a Case Report

The use of dexmedetomidine with concurrent scalp block is increasingly being utilized as an effective and safe anesthetic approach for awake craniotomy (AC). Dexmedetomidine is an alpha-2 adrenergic receptor (α2-AR) agonist with dose-dependent sedative, analgesic, and anxiolytic properties while preserving respiratory function. The challenge with the use of dexmedetomidine arises when the patient has a clonidine allergy, which is also an α2-AR agonist. Currently, there is no published literature regarding the use of dexmedetomidine in a patient allergic to clonidine. A 48-year-old male with chronic obstructive pulmonary disease, obstructive sleep apnea, and body mass index of 54 with clonidine allergy presents for an AC. Given the goals of the surgery and the patient’s comorbidities, we planned for monitored anesthesia care with intravenous (IV) dexmedetomidine, remifentanil, and propofol. We discussed the use of dexmedetomidine with the patient and the potential risk of allergic reaction given his allergy to clonidine. The patient understood the risk and consented to the anesthetic plan. AC was successfully performed with IV dexmedetomidine, remifentanil, and propofol. Although both dexmedetomidine and clonidine have some functional similarities in terms of acting on the central and peripheral nervous system, there are marked differences between the two based on chemical structure, receptor affinity, and metabolism of the drug. This case highlights the successful use of dexmedetomidine in a patient with known allergy of rash to clonidine.

Sublingual dexmedetomidine: repurposing an anesthetic as an anti-agitation agent

ABSTRACT Introduction Especially when acutely ill, individuals with schizophrenia and bipolar disorder can present with agitated behavior. The initial approach to agitation management are non-pharmacologic strategies such as verbal de-escalation techniques; however, pharmacologic interventions may be needed. Dexmedetomidine is a selective alpha-2 adrenergic receptor agonist, and a sublingual formulation has been approved in the US for the treatment of agitation associated with schizophrenia and bipolar disorder in adults. Areas covered The authors review the published literature on sublingual dexmedetomidine using the US National Library of Medicine’s PubMed.gov resource. Pharmacodynamics, pharmacokinetics, and efficacy and tolerability findings are summarized. The authors also provide a discussion to its potential place in the treatment armamentarium. Expert opinion Sublingual dexmedetomidine is an effective and well-tolerated pharmacologic option for the treatment of agitation associated with schizophrenia and bipolar disorder. The sublingual method of administration allows for a rapid onset of action with treatment effects beginning as early as 20 minutes after administration. Adverse effects include somnolence, hypotension, oral paresthesia, hypoesthesia, and dry mouth. Further study will be needed to evaluate sublingual dexmedetomidine in real-world patients receiving concomitant psychotropic medications.

Evaluation of in vivo MRI for detecting midodrine-induced arteritis in rats.

There are no specific and sensitive biomarkers for arteritis, and the occurrence of arteritis in nonclinical toxicological studies of a candidate drug makes development of the drug very difficult. However, we showed in a previous study that the high signal intensity region around the artery on magnetic resonance imaging (MRI) could be a candidate biomarker for detection of arteritis. The present study was conducted to clarify the details of midodrine hydrochloride (MH)-induced arteritis lesions and whether arteritis induced by a mechanism other than the vasodilatory effect, which was evaluated in a previous study, could be detected by MRI. MH is a selective peripherally acting alpha-1 adrenergic receptor agonist, known to induce arteritis due to its vasoconstrictor action, but there is not enough information about MH-induced arteritis. Based on the data obtained under multiple dosing conditions, MH was administered subcutaneously to each rat once daily for 2 days at a dose level of 40mg/kg/day for MRI assessment. The mesenteric arteries were examined using in vivo MRI at 1day or 7 days after administration of the final dose and examined histopathologically. On the day after the final dose, high signal intensity region around the artery was observed in animals with minimal perivascular lesions confirmed by histopathology and not observed in an animal without histological changes. On the 7th day after the final dose, no abnormality was observed in histopathological examinations and no high signal intensity regions were observed by MRI in any animal. In conclusion, although further investigation is needed to confirm that high signal intensity is a reliable biomarker for humans, it is suggested that high signal intensity around the artery could be a versatile candidate biomarker with high specificity and sensitivity.

Compared Dexmedetomidine and Fentanyl on Sensory-Motor Block in Unilateral Intrathecal Anesthesia of Lower-limbs Orthopedic Surgeries: A Randomized Duble-blind Trials

Background: One of the alternatives for lower-limb orthopedic surgery is spinal anesthesia. It can affect the hemodynamic status and cause the prolonged motor and sensory blocks, as well as urinary retention, which are less common in the unilateral technique. Different drugs are used to improve the quality of the block and reduce its complications. Dexmedetomidine, a selective alpha-2 adrenergic receptor agonist, and fentanyl, an opioid medication, could administration as an adjuvant to increase the intrathecal block quality. Hence, this study aimed to compare unilateral spinal anesthesia with bupivacaine/dexmedetomidine (BD) and bupivacaine/fentanyl (BF) regimes on the sensory-motor block among patients with lower-limb orthopedic surgeries. Materials and Method: This randomized, double-blind clinical trial was performed on 36 patients who underwent lower-limb orthopedic surgeries in Qaem Hospital, Mashhad, Iran. The patients were randomly divided into two groups. Patients who received 5.7 mg hyperbaric bupivacaine 0.5% plus 10 µg fentanyl (BF group) or 5 µg dexmedetomidine (BD group) were administered for inducing unilateral spinal anesthesia. Patients and investigators responsible for data collection were not awarded from allocation groups. The sensory-motor block level, duration, postoperative analgesia, and complications were recorded and compared between the two groups. Results: No significant difference was observed between the two groups in hemodynamic changes (i.e., systolic and diastolic blood pressure and heart rate) before and after the blockage (P˃0.05). Also, there was no difference in the sensory-motor block level and anesthesia-related complications between BF and BD groups (P˃0.05). Conclusion: In patients for whom the use of opioids for unilateral spinal anesthesia is contraindicated, dexmedetomidine could be considered an appropriate alternative.

Dexmedetomidine alleviates intestinal barrier dysfunction and inflammatory response in mice via suppressing TLR4/MyD88/NF-κB signaling in an experimental model of ulcerative colitis.

Ulcerative colitis (UC) is a nonspecific intestinal inflammatory disease. Dexmedetomidine (DEX) is a selective alpha 2-adrenergic receptor agonist commonly used for analgesia and sedation in intensive care units. Herein, the role and mechanism of DEX in dextran sulfate sodium (DSS)-induced colitis was explored. A murine model of DSS-induced colitis was established by adding 3.5% (w/v) DSS in drinking water to C57BL/6J female mice. The severity of colitis was measured by the disease activity index (DAI) score, colon length and body weight of mice. The serum concentration and mRNA levels of inflammatory cytokines in colon tissues were assessed by ELISA and RT-qPCR, respectively. Protein levels of apoptotic markers, tight junction proteins and genes involved in the TLR4/MyD88/NF-κB signaling were quantified utilizing Western blotting. The pathological changes of colon tissues were evaluated by hematoxylin-eosin (HE) staining and histological score. Intestinal permeability in vivo was assessed by fluorescein isothiocyanate (FITC)-dextran (FITC-D) administration. TUNEL assay was used to determine cell apoptosis in the intestinal epithelium. DSS administration resulted in weight loss, shortening of the colon, increased DAI score, histological abnormalities, and increased serum FITC-D levels in mice, all of which were reversed by DEX injection. Moreover, DEX attenuated DSS-triggered inflammatory response, intestinal barrier injury and intestinal epithelial cell apoptosis. Mechanically, DEX inactivated the TLR4/MyD88/NF-κB signaling in the colon tissues. DEX exerts beneficial effects against the intestinal barrier dysfunction, inflammatory response, and apoptosis of intestinal epithelial cells via inactivation of the TLR4/MyD88/NF-κB signaling in mice with DSS-induced colitis.

Treatment of ADHD: Drugs, psychological therapies, devices, complementary and alternative methods as well as the trends in clinical trials.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders having a high influence on social interactions. The number of approved treatments and clinical trials for ADHD have increased markedly during the recent decade. This analytical review provides a quantitative overview of the existing pharmacological and non-pharmacological methods of ADHD treatments investigated in clinical trials during 1999-2021. A total of 695 interventional trials were manually assessed from clinicaltrial.gov with the search term « ADHD», and trial data has been used for analysis. A clear majority of the studies investigated non-pharmacological therapies (∼80%), including many behavioral options, such as social skills training, sleep and physical activity interventions, meditation and hypnotherapy. Devices, complementary and other alternative methods of ADHD treatment are also gaining attention. The pharmacological group accounts for ∼20% of all the studies. The most common drug classes include central nervous system stimulants (e.g., methylphenidate hydrochloride, lisdexamfetamine dimesylate, amphetamine sulfate, mixed amphetamine salts, a combination of dexmethylphenidate hydrochloride and serdexmethylphenidate chloride), selective noradrenaline reuptake inhibitors (atomoxetine, viloxazine), and alpha2 adrenergic receptor agonists (guanfacine hydrochloride, clonidine hydrochloride). Several studies investigated antidepressants (e.g., bupropion hydrochloride, vortioxetine), and atypical antipsychotics (e.g., quetiapine, aripiprazole) but these are yet not approved by the FDA for ADHD treatment. We discuss the quantitative trends in clinical trials and provide an overview of the new drug agents and non-pharmacological therapies, drug targets, and novel treatment options.