Analgesic efficacy of CR4056, a novel imidazoline-2 receptor ligand, in rat models of inflammatory and neuropathic pain

Two decades of investigations have failed to unequivocally clarify the functions and the molecular nature of imidazoline-2 receptors (I2R). However, there is robust pharmacological evidence for the functional modulation of monoamino oxidase (MAO) and other important enzyme activities by I2 site ligands. Some compounds of this class proved to be active experimental tools in preventing both experimental pain and opioid tolerance and dependence. Unfortunately, even though these compounds bind with high potency to central I2 sites, they fail to represent a valid clinical opportunity due to their pharmacokinetic, selectivity or side-effects profile. This paper presents the preclinical profile of a novel I2 ligand (2-phenyl-6-(1H-imidazol-1yl) quinazoline; [CR4056]) that selectively inhibits the activity of human recombinant MAO-A in a concentration-dependent manner. A sub-chronic four day oral treatment of CR4056 increased norepinephrine (NE) tissue levels both in the rat cerebral cortex (63.1% ±4.2%; P < 0.05) and lumbar spinal cord (51.3% ± 6.7%; P < 0.05). In the complete Freund’s adjuvant (CFA) rat model of inflammatory pain, CR4056 was found to be orally active (ED50 = 5.8 mg/kg, by mouth [p.o.]). In the acute capsaicin model, CR4056 completely blocked mechanical hyperalgesia in the injured hind paw (ED50 = 4.1 mg/kg, p.o.; ED100 = 17.9 mg/kg, p.o.). This effect was dose-dependently antagonized by the non-selective imidazoline I2/α2 antagonist idazoxan. In rat models of neuropathic pain, oral administration of CR4056 significantly attenuated mechanical hyperalgesia and allodynia. In summary, the present study suggests a novel pharmacological opportunity for inflammatory and/or neuropathic pain treatment based on selective interaction with central imidazoline-2 receptors

TCT-260 Which is the Ideal Revascularization Strategy in Patients Presenting with Acute Coronary Syndrome and Proximal LAD Stenosis? Results from the ACUITY Study

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Стан та перспективи конкурентоспроможності галузі національного господарства в умовах глобалізації

Метою дослідження є узагальнення нових теоретичних положень розвитку галузей економіки в умовах глобалізації, визначення загальних конкурентних переваг хімічної галузі України та практичних напрямів сучасного розвитку економіки країни

TCT-481 Treatment of "resistant" in-stent restenosis in the drug-eluting era: comparison of repeat stent versus balloon only strategy

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Clinical outcome with different doses of low-molecular-weight heparin in patients hospitalized for COVID-19

A pro-thrombotic milieu and a higher risk of thrombotic events were observed in patients with CoronaVirus disease-19 (COVID-19). Accordingly, recent data suggested a beneficial role of low molecular weight heparin (LMWH), but the optimal dosage of this treatment is unknown. We evaluated the association between prophylactic vs. intermediate-to-fully anticoagulant doses of enoxaparin and in-hospital adverse events in patients with COVID-19. We retrospectively included 436 consecutive patients admitted in three Italian hospitals. Outcome according to the use of prophylactic (4000IU) vs. higher (>4000IU) daily dosage of enoxaparin was evaluated. The primary end-point was in-hospital death. Secondary outcome measures were in-hospital cardiovascular death, venous thromboembolism, new-onset acute respiratory distress syndrome (ARDS) and mechanical ventilation. A total of 287 patients (65.8%) were treated with the prophylactic enoxaparin regimen and 149 (34.2%) with a higher dosing regimen. The use of prophylactic enoxaparin dose was associated with a similar incidence of all-cause mortality (25.4% vs. 26.9% with the higher dose; OR at multivariable analysis, including the propensity score: 0.847, 95% CI 0.400-0.1.792; p=0.664). In the prophylactic dose group, a significantly lower incidence of cardiovascular death (OR 0.165), venous thromboembolism (OR 0.067), new-onset ARDS (OR 0.454) and mechanical intubation (OR 0.150) was observed. In patients hospitalized for COVID-19, the use of a prophylactic dosage of enoxaparin appears to be associated with similar in-hospital overall mortality compared to higher doses. These findings require confirmation in a randomized, controlled study

AtopyReg®, the Prospective Italian Patient Registry for Moderate-to-Severe Atopic Dermatitis in Adults: Baseline Demographics, Disease Characteristics, Comorbidities, and Treatment History

background and objective atopyReg((R)) is a multicenter, prospective, observational, non-profit cohort study on moderate-tosevere atopic dermatitis in adults promoted in 2018 by the Italian society of dermatology and Venereology (SIDeMaST). we aimed to describe baseline demographics, disease characteristics, comorbidities, and therapeutic data of adult patients affected by moderate-to-severe atopic dermatitis.methods patients were selected based on the following inclusion criteria: age &gt;= 18 years; eczema area and severity Index score &gt;= 7 or a numeric rating scale sleep loss score = 7, or a dermatology life quality Index score &gt;= 10. score &gt;= 16 or localization in visible or sensitive areas (face, neck, hands, or genitalia), or a numeric rating scale itchDemographic and clinical data at baseline were recorded and analyzed. results a total of 1170 patients (male 51.1%; mean age: 44.7 years; range 18-90 years) were enrolled by 12 Italian dermatology units between January 2019 and november 2022. skin lesions were eczematous in 83.2% of patients, the most involved site were the flexures (53.9%), face (50.9%), and neck (48.0%). mean eczema area and severity Index score was 22.3, mean dermatology life quality Index value was 17.6, mean patient oriented Eczema measure score was 13.1, and mean numeric rating scale itch and sleep loss scores were 7.6 and 5.9, respectively. previous systemic therapies were corticosteroids in 77.7% of patients, antihistamines in 50.3% of patients, and cyclosporine A in 42.6% of patients.conclusions this baseline data analysis deriving from atopyReg((R)) provides real-life evidence on patients with moderate-to-severe atopic dermatitis in Italy confirming the high burden of atopic dermatitis with a significant impact on patients' quality of life