Antinociceptive and anti-inflammatory effects of hydrazone derivatives and their possible mechanism of action in mice.

Pain and inflammation are unpleasant experiences that usually occur as a result of tissue damage. Despite the number of existing analgesic drugs, side effects limit their use, stimulating the search for new therapeutic agents. In this sense, five hydrazone derivatives (H1, H2, H3, H4, and H5), with general structure R1R2C = NNR3R4, were synthesized with molecular modification strategies. In this paper, we describe the ability of hydrazone derivatives to attenuate nociceptive behavior and the inflammatory response in mice. Antinociceptive activity was evaluated through acetic acid-induced writhing and formalin-induced nociception tests. In both experimental models, the hydrazone with the greatest potency (H5) significantly (p < 0.05) reduced nociceptive behavior. Additionally, methods of acute and chronic inflammation induced by different chemicals (carrageenan and histamine) were performed to evaluate the anti-inflammatory effect of H5. Moreover, molecular docking analysis revealed that H5 can block the COX-2 enzyme, reducing arachidonic acid metabolism and consequently decreasing the production of prostaglandins, which are important inflammatory mediators. H5 also changes locomotor activity. In summary, H5 exhibited relevant antinociceptive and anti-inflammatory potential and acted on several targets, making it a candidate for a new multi-target oral anti-inflammatory drug.

Improving treatment outcomes for leprosy in Pernambuco, Brazil: a qualitative study exploring the experiences and perceptions of retreatment patients and their carers.

BACKGROUND: Brazil has a high leprosy burden and poor treatment outcomes (TOs), manifesting in high relapse rates. Pernambuco, an impoverished Brazilian state suffering notable geographical health inequalities, has 'hyperendemic' leprosy. Although current literature identifies barriers and facilitators influencing leprosy treatment compliance, inadequate investigation exists on other factors influencing TOs, including carers' roles and psycho-dermatological impact. This qualitative study explores experiences and perceptions of leprosy patients and their carers in Pernambuco, Brazil; to identify location-specific factors influencing TOs, and consequently inform future management. METHODS: 27, semi-structured, in-depth interviews were conducted with 14 patients and 13 carers. Participants were recruited using maximum variation and snowball sampling from three clinics in Petrolina, Pernambuco. Transcripts and field notes from both participant groups were separately analysed using conventional thematic and deviant case analysis. The University of Birmingham Internal Research Ethics Committee and Instituto Lauro de Souza Lima provided ethical approval. RESULTS: Two homologous sets of four, primary, interdependent themes influencing leprosy TOs emerged: 'personal factors'; 'external factors'; 'clinical factors'; and 'the healthcare professional (HCP)-patient-carer relationship'. Poor participant knowledge and lack of symptomatic relief caused patients to distrust treatment. However, because participants thought HCP-led interventions were vital for optimal TOs, patients were effectively persuaded to adhere to pharmaceutical treatments. High standard patient and population education facilitated treatment engagement by encouraging evidence-based medicine belief, and dispelling health myths and stigma. Healthcare, on occasions, was perceived as disorganised, particularly in resource-scarce rural areas, and for those with mental health needs. Participants additionally experienced incorrect/delayed diagnoses and poor contact tracing. Leprosy's negative socio-economic impact on employment - together with stigma, dependency and changing relationships - caused altered senses of identity, negatively impacting TOs. Better dialogue between patients, HCPs and carers facilitated individualised patient support. CONCLUSION: This study highlights the importance of: effective evidence-based leprosy education; communication between HCPs, patients and carers; state-funded support; and healthcare resource distribution. These findings, if prioritised on governmental scales, provide the valuable insight needed to inform location-specific management strategies, and consequently improve TOs. Future research should evaluate the effectiveness of these implementations. Failure to address these findings will hinder regional elimination efforts.

Cannabis and Cannabinoids on Treatment of Inflammation: A Patent Review.

BACKGROUND: The inflammatory process is a physiological response to a vast number of harmful stimulus that takes place in order to restore homeostasis. Many drugs used in pharmacotherapy are effective to control inflammatory responses, however, there is a range of adverse effects attributed to steroidal and non-steroidal anti-inflammatory drugs (NSAIDs). In this sense, herbal medicine and derivatives have gained more attention because of their effectiveness and safety, showing the importance of medicinal plants, especially the Cannabis genus and the cannabinoid derivatives. OBJECTIVE: The aim of this prospection was to identify data related to patents involving Cannabis and cannabinoids for the treatment of inflammation. METHODS: To do so, a search for patents was conducted to evaluate the anti-inflammatory activity of Cannabis and cannabinoids. Four specialized databases for patent research were consulted using the terms "cannabis", "cannabidiol", "cannabinoids" and "THC" associated with "inflammation". RESULTS: A total of 370 patents were found, of which 17 patents met the inclusion criteria. Although reports show synergistic effects of the plant components, patents involving Cannabis and cannabinoids focus on isolated substances (CBD e THC). CONCLUSION: However, patents related to Cannabis and cannabinoids are promising for future use of the plant or its derivatives on the treatment of inflammation.