Reflectance confocal microscopy - Consensus terminology glossary in Brazilian Portuguese for normal skin, melanocytic and non-melanocytic lesions

Abstract Background: Currently, there is no uniform and official terminology in Portuguese for reflectance confocal microscopy analysis, despite the increasing number of Brazilian dermatologists using this new tool. Objective: To present the terminology in Brazilian Portuguese for the description of reflectance confocal microscopy and establish the first Brazilian consensus on terms related to normal skin and cutaneous tumors. Methods: 10 Brazilian specialists from different institutions and states of Brazil were selected to evaluate the best corresponding terms in Portuguese for normal skin, melanocytic and non-melanocytic tumors. The terms used were translated from international consensuses in the English language. The modified Delphi method was used to create the consensus in 3 steps. Results: The terms considered the most appropriate in the Portuguese language to describe the findings of normal skin, melanocytic and non-melanocytic lesions in the reflectance confocal microscopy analysis were presented. Study limitations: The limitations of the present study include the number of participants and limited regional representation (only two of the five Brazilian regions were represented). Conclusion: This Brazilian consensus represents an opportunity for dermatologists and physicians specializing in cutaneous oncology to become familiar with reflectance confocal microscopy, propagating the technique in clinical and research environments to stimulate national and international publications on this subject.

Reflectance confocal microscopy - Consensus terminology glossary in Brazilian Portuguese for normal skin, melanocytic and non-melanocytic lesions.

BACKGROUND: Currently, there is no uniform and official terminology in Portuguese for reflectance confocal microscopy analysis, despite the increasing number of Brazilian dermatologists using this new tool. OBJECTIVE: To present the terminology in Brazilian Portuguese for the description of reflectance confocal microscopy and establish the first Brazilian consensus on terms related to normal skin and cutaneous tumors. METHODS: 10 Brazilian specialists from different institutions and states of Brazil were selected to evaluate the best corresponding terms in Portuguese for normal skin, melanocytic and non-melanocytic tumors. The terms used were translated from international consensuses in the English language. The modified Delphi method was used to create the consensus in 3 steps. RESULTS: The terms considered the most appropriate in the Portuguese language to describe the findings of normal skin, melanocytic and non-melanocytic lesions in the reflectance confocal microscopy analysis were presented. STUDY LIMITATIONS: The limitations of the present study include the number of participants and limited regional representation (only two of the five Brazilian regions were represented). CONCLUSION: This Brazilian consensus represents an opportunity for dermatologists and physicians specializing in cutaneous oncology to become familiar with reflectance confocal microscopy, propagating the technique in clinical and research environments to stimulate national and international publications on this subject.

Survival in patients undergoing surgical resection for brain metastasis from lung cancer and utility of different prognostic scales.

Brain metastases (BM) from lung cancer are among the most common intracranial tumors. Several studies have published scales to estimate the survival of patients with BM. Routine access to molecular diagnostics and modern oncologic treatments, including targeted therapy and immunotherapy, is limited in low- and middle-income countries (LMICs); therefore, incorporating them into recent prognostic scales may diminish the reliability of the scales in LMICs. This retrospective study aimed to determine the survival of 55 patients who were surgically treated for BM from lung cancer at a Brazilian public tertiary teaching hospital between 2012 and 2022. We determined clinical factors associated with survival, and compared observed survival rates with the estimated survival on prognostic scales. The mean overall survival (OS) was 9.3 months (range:0.2-76.5). At univariate analysis, female sex and improved postoperative Karnofsky performance status (KPS) score were associated with longer survival. The median survival did not differ between groups when classified using the Graded Prognostic Assessment (GPA)-2008, Lung-molecular GPA-2017, and Lung-GPA-2021 scales. According to the Diagnosis-Specific (DS)-GPA-2012 scale, there was a significant difference between the groups. In the multivariate Cox regression survival analysis, a higher DS-GPA-2012 and improved postoperative KPS score remained significantly associated with longer survival. In conclusion, this cohort showed a mean OS of < 1 year. Improved KPS score after surgery was associated with increased survival. This cohort DS-GPA scale demonstrated the highest concordance with observed survival, indicating its potential as a valuable tool for patient stratification in surgical treatment decision-making in LMICs.

Junctional Nevus and Early Melanoma on Sun-Damaged Skin of the Head/Neck: a Clinico-Pathologic Challenge.

INTRODUCTION: Melanoma on the head/neck area can show subtle clinical, dermoscopic and histologic features at early stages, being difficult to differentiate from junctional nevi. OBJECTIVES: This case series aims to raise awareness on the topic of misdiagnosis of early lentigo maligna as junctional nevi. METHODS: From the databases of three pigmented lesion clinics in Italy, Australia, and France, we retrieved all cases of lesions of the head/neck area with an initial histopathologic diagnosis of junctional nevus (JN) or dysplastic junctional nevus (DJN) which subsequently recurred and were ultimately diagnosed as melanoma. Moreover, we also retrieved those cases with an initial diagnosis of JN/DJN made on a partial biopsy that were diagnosed as melanoma after complete surgical removal. RESULTS: Here we report 14 cases in which the initial histologic diagnosis was junctional nevus or dysplastic junctional nevus. The lesions recurred over time with a final diagnosis of lentigo maligna. CONCLUSIONS: Clinicians should critically question a given histologic diagnosis of junctional or dysplastic junctional nevus on the head/neck area if the clinical or dermoscopic features are discordant. Clinico-pathologic correlation is the best way to increase diagnostic accuracy and optimize management for the patient.

Confocal microscopy, dermoscopy, and histopathology features of atypical intraepidermal melanocytic proliferations associated with evolution to melanoma in situ.

BACKGROUND: Atypical intraepidermal melanocytic proliferations (AIMP) is a descriptive term sometimes applied to biopsies that do not fulfill diagnostic criteria of melanoma. They are common on sun-damaged skin, but their definition and management are controversial. OBJECTIVE: To describe dermoscopic (DS), reflectance confocal microscopic (RCM) and histopathological features of AIMP and identify features associated with subsequent melanoma in situ (MIS). METHODS: A retrospective analysis of AIMP lesions correlated with patient outcome at two melanoma tertiary centers between 2005 and 2015. RESULTS: Thirty-four patients were included. Nine (26%) patients had MIS in subsequent biopsies. Predictors of later MIS were target-like pattern (OR:12.0 [CI: 1.23, 117.41]; P = 0.032) and high-density vascular network (OR:12 [CI: 1.23-117.41], P: 0.032) on DS, and presence of dendritic cells touching each other (OR:9.1 [CI: 1.54, 54.59], P = 0.014) on RCM. Clinical predictors of worse outcome included a previous history of MIS at the same site. Radiotherapy for AIMP had a high failure rate (all patients presented with recurrent disease, three as AIMP and two as MIS). CONCLUSIONS: Considering that most cases in this series received non-surgical treatment at baseline, we recommend close monitoring for lesions with target-like pattern and density vascular network on DS and treatment for lesions with progression of atypia and/or with "confluent" dendritic cells on RCM. Although the number of patients in this series is very low, early surgery is recommended for MIS cases that recur as AIMP.

Reflectance confocal microscopy (RCM)-based criteria for progression of lower-lip squamous cell carcinoma: A prospective study.

BACKGROUND: Actinic cheilitis (AC) presents as a diffuse clinical-histopathological alteration throughout the lower lip. OBJECTIVES: To analyze AC lesions using reflectance confocal microscopy (RCM) and evaluate criteria for the early diagnosis of incipient squamous cell carcinoma (SCC). METHODS: This prospective study comprised cases of clinically diagnosed AC. RCM was performed over the entire extension of the lower lip. The sites that showed the highest degree of morphological alteration by RCM, according to established criteria for AC and SCC, were biopsied. The RCM findings and histopathology were correlated to establish the precise and early diagnosis of SCC. RESULTS: A total of 61 cases that had been clinically diagnosed with AC were included. The RCM findings that correlated independently with SCC were: nonedged papillae (sensitivity 84% and specificity 88%, p < 0.0001, and OR 42), cell-filled papillae (sensitivity 82% and specificity 93%, p < 0.0001, and OR 71.3), inflammation (sensitivity 68% and specificity 68%, p = 0.0163, and OR 4.8), large and roundish cells in the lamina propria (sensitivity 65% and specificity 100%, p < 0.0001, and OR infinity), and nests in the lamina propria (sensitivity 54% and specificity 100%, p < 0.0001, and OR infinity). An independent histopathological analysis classified the cases as partial epithelial dysplasia (25 cases, 41%) and SCC (36, 59%), and in 57 cases (94%), the results agreed with the categorization that was rendered by the RCM exam. CONCLUSIONS: RCM can be used to monitor AC cases, guide the biopsy site, and identify the early progression of AC to SCC with good sensitivity and specificity.

Entre incêndios e prevenção: sífilis congênita no território de Franco da Rocha / Between fires and prevention: congenital syphilis in the territory of Franco da Rocha

Introdução: A Sífilis é uma das IST's mais antigas já datadas, ela é causada pela bactéria Treponema pallidum. Como condição de diagnóstico e tratamentos bem delimitados, é uma infecção curável, mas que segue sendo um grande problema de saúde pública, como quando ocorre na sua modalidade gestacional, que não tratada ou tratada de forma inadequada pode ser transmitida verticalmente para o feto, podendo desencadear má formação congênita. Objetivo: Contribuir para produção de conhecimento e dar base científica para ações que visem a diminuição da sífilis congênita no território de Franco da Rocha e conhecer a percepção dos profissionais da atenção básica sobre a sífilis congênita e quais são os principais desafios que enfrentam para combatê-la e fornecer um bom atendimento aos usuários. Metodologia: Trata-se de um estudo qualitativo, que parte de duas etapas metodológicas. As entrevistas com gestores e profissionais de saúde, que contribuíram para subsidiar formas de entender a dinâmica dos profissionais, assim como apreender as ações em saúde no município, principalmente as relacionadas ao pré-natal e ao enfrentamento da sífilis congênita e a busca de boas práticas para subsidiar a discussão. Toda análise e interpretação dos materiais de entrevista teve como embasamento teórico a perspectiva sócio-histórica, que entende as narrativas dos sujeitos como sendo construções históricas. Resultados e Discussão: Os resultados estão organizados em categorias, tais surgiram a partir da organização das respostas dos entrevistados às perguntas que compõem o roteiro de entrevista. Cada agrupamento profissional teve um roteiro de entrevista personalizado, mas com questões comuns a todos os grupos. As perguntas possibilitaram a leitura da realidade do município de Franco da Rocha em relação à Sífilis, através das vivências dos profissionais de saúde, tanto da ponta do serviço, quanto da gestão. Conclusão: O trabalho possibilitou que se discutisse as barreiras e as fortalezas impostas a realização de um bom pré-natal, e, por consequência, a um bom acompanhamento (diagnóstico e tratamento) da sífilis gestacional. Tais versaram sobre como o desempenho profissional (alta rotatividade e adequação de diretrizes e protocolos clínicos), questões sociais, como o machismo, as desigualdades estruturantes, como o acesso aos serviços, educação sexual e permanente, atravessam a questão da sífilis congênita e aponta para nortes de atuação.

Long-term follow-up of patients undergoing decompressive hemicraniectomy for malignant stroke: Quality of life and caregiver's burden in a real-world setting.

BACKGROUND AND PURPOSE: Decompressive hemicraniectomy is a life-saving procedure for the treatment of space-occupying middle cerebral artery infarctions (malignant stroke); however, patients may survive severely disabled. Comprehensive data on long-term sequelae outside randomized controlled trials are scarce. METHODS: We retrospectively evaluated the survival rates, quality of life, ability to perform activities of daily living, and caregiver burden of 61 patients (aged from 37 to 83) who had previously undergone decompressive hemicraniectomy for malignant stroke between 2012 and 2017. RESULTS: The mortality rate was higher among patients older than 60 years than among younger patients (71.0 % vs 36.7 %, p = 0.007; odds ratio 4.222, 95 % confidence interval 1.443-12.355). The mean survival time was 37.9 ± 6.0 months for 19 survivors of the younger group and 22.6 ± 5.7 months for 9 survivors of the older group. Among the 28 surviving patients, 22 (78.6 %) were interviewed, and we found that age was a determining factor for functional outcome (Barthel indices of 65.7 ± 10.6 for younger patients vs 48.0 ± 9.3 for older patients, p < 0.001), but not for quality of life. The caregiver burden was significantly correlated (R = -0.53, p < 0.01) with the severity of disability and age (R = 0.544, p = 0.011) of the patients. CONCLUSION: Our findings show that the degree of impairment, as well as caregiver burden, is higher in patients older than 60 years than in younger patients.

In vivo confocal microscopy of dermoscopic suspicious lesions in patients with xeroderma pigmentosum: A cross-sectional study.

BACKGROUND: Xeroderma pigmentosum (XP) is a rare genetic disease characterized by extreme photosensitivity, resulting in a higher incidence of cutaneous tumors. Reflectance confocal microscopy (RCM) is a noninvasive imaging method for diagnosing cutaneous lesions. OBJECTIVE: To explore the application of RCM in the follow-up of patients with XP. METHODS: Patients with XP underwent RCM for suspicious lesions from January 2010 through April 2019. Lesions with malignant RCM features were excised, and the results were compared with their histopathologic features. Benign lesions on RCM were monitored every 3 months. We recorded the confocal features that were related to malignancy and specifically to melanoma. RESULTS: A total of 61 suspicious lesions from 13 patients with XP were included. Thirty-three lesions (54%) were malignant (14 melanomas, 15 basal cell carcinomas, and 4 squamous cell carcinomas). Nonvisible papillae (OR, 11.8; 95% CI, 2.6-53.1; P = .001) and atypical cells at the dermoepidermal junction (OR, 11.7; 95% CI, 2.7-50.3; P = .001) were independent predictors of malignancy. LIMITATIONS: There were limited numbers of patients and lesions. Most cases were retrospectively included, and some did not have a histologic analysis. CONCLUSIONS: RCM is a valuable tool in the follow-up of patients with XP, reducing the need for excisions by 35%.

RP-HPLC and LC-MS-MS determination of a bioactive artefact from Ipomoea pes-caprae extract

Abstract Solvents play important and critical role in natural product chemistry and could generate artefacts during the extraction and purification of metabolites from a biological matrix. This study aimed to correlate the chromatographic profile with biological activity of Ipomoea pes-caprae (L.) R. Br., Convolvulaceae, extracts obtained with hydroethanolic extraction. Thus, aerial parts of I. pes-caprae were extracted with different concentration of ethanol (50, 70 and 90°GL) and the obtained extracts were analysed by HPLC-UV. HPLC data were studied employing chemometrics to discriminate the samples. Moreover these samples were further characterized by using UPLC-QTOF/MS data. The extracts were also biomonitored through the paw-oedema and spontaneous nociception induced by trypsin in mice. Different chromatographic profiles were obtained and the exploratory analysis clearly revealed higher level of ethyl caffeate in extracts of lower strength of ethanol (50°GL). This compound was suggested to be an artefact formed by transesterification of caffeoylquinic acid derivatives present in the plant, once it was not observed when other solvents were employed. During the biological assay, only the extract obtained with ethanol 50°GL presented significant inhibition of inflammation (45 ± 9%) and nociception (24 ± 3%). Ethyl caffeate seems to be linked to the anti-inflammatory effect since it reduced 86 ± 5% of paw-oedema induced by trypsin. Artefacts could contribute to the biological activity of herbal preparations and consequently lead to misinterpretation of the results.

Correction to: The kinin B1 and B2 receptors and TNFR1/p55 axis on neuropathic pain in the mouse brachial plexus.

Unfortunately, the Fig. 7 was wrongly downloaded in the original publication.

The kinin B1 and B2 receptors and TNFR1/p55 axis on neuropathic pain in the mouse brachial plexus.

Tumour necrosis factor (TNF) and kinins have been associated with neuropathic pain-like behaviour in numerous animal models. However, the way that they interact to cause neuron sensitisation remains unclear. This study assessed the interaction of kinin receptors and TNF receptor TNFR1/p55 in mechanical hypersensitivity induced by an intraneural (i.n.) injection of rm-TNF into the lower trunk of brachial plexus in mice. The i.n. injection of rm-TNF reduced the mechanical withdrawal threshold of the right forepaw from the 3rd to the 10th day after the injection, indicating that TNF1/p55 displays a critical role in the onset of TNF-elicited neuropathic pain. The connection between TNF1/p55 and kinin B1 and B2 receptors (B1R and B2R) was confirmed using both knockout mice and mRNAs quantification in the injected nerve, DRG and spinal cord. The treatment with the B2R antagonist HOE 140 or with B1R antagonist des-Arg9-Leu8-BK reduced both BK- and DABK-induced hypersensitivity. The experiments using kinin receptor antagonists and CPM inhibitor (thiorphan) suggest that BK does not only activate B2R as an orthosteric agonist, but also seems to be converted into DABK that consequently activates B1R. These results indicate a connection between TNF and the kinin system, suggesting a relevant role for B1R and B2R in the process of sensitisation of the central nervous systems by the cross talk between the receptor and CPM after i.n. injection of rm-TNF.

Aleurites moluccanus and its main active constituent, the flavonoid 2″-O-rhamnosylswertisin, in experimental model of rheumatoid arthritis.

ETHNOPHARMMACOLOGICAL RELEVANCE: Aleurites moluccana is used in folk medicine to treat pain, fever, asthma, hepatitis, gastric ulcer and inflammatory process in general, and the nut oil had been topically applied to treat arthritis and other joint pain, however the seeds are classified as toxic for oral use. AIM: Faced with the need for new alternative to treat the symptoms and modify rheumatoid arthritis (RA) the aim of this work was to evaluate the effects of A. moluccanus' leaves dried extract in rats and mice submitted to complete Freund adjuvant (CFA)-induced RA. MATERIAL AND METHODS: Wistar Rats and Swiss mice were submitted to CFA-induced RA in the right hindpaw. They received A. moluccanus extract (orally; p.o.), dexamethasone (subcutaneously), 2″-O-rhamnosylswertisin (p.o.) or vehicle (p.o.), from the 14th day after the CFA injection for up to 8 days. The mechanical hypersensitivity was evaluated using the von Frey filaments and the paw-oedema was measured using a plethysmometer. The rats' injected hindpaw was used to perform the histological analysis. RESULTS: A. moluccanus was able to significantly reduce the mechanical hypersensitivity in both ipsi- and contralateral hindpaws of mice injected with CFA, in a dose dependent manner. Furthermore, the paw-oedema was progressively reduced by A. moluccanus. Similar results were obtained for the positive-control drug dexamethasone and the isolated compound 2″-O-rhamnosylswertisin. Besides the effects mentioned above, the extract was also effective to repair the joint damage in CFA-induced RA rats, including reduction of fibrosis, cartilage degradation and bone erosion scores. CONCLUSION: These results together with the literature data reinforce the anti-hypersensitivity and anti-inflammatory activity of A. moluccanus extract. Part of the observed effects is due to the presence of the compound 2″-O-rhamnosylswertisin. The fact that the extract acted as a disease modifier point this herbal product as a promisor and safe tool to treat RA and other associated chronic diseases.

Local administration of mangiferin prevents experimental inflammatory mechanical hyperalgesia through CINC-1/epinephrine/PKA pathway and TNF-α inhibition.

Steroidal and non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to control inflammatory pain, but there is a risk of gastrointestinal bleeding and increased heart failure risk. The search for new drugs remains ongoing, and natural products are a source for potential new compounds. Mangiferin, a natural xanthone C-glucoside, has demonstrated biological activity, including anti-inflammatory and analgesic properties, but it's mechanisms are poorly understood. In this study, we investigated the mechanisms underlying the anti-inflammatory and analgesic effects of local administration of mangiferin. We employed an electronic von Frey apparatus to evaluate mechanical hyperalgesia induced by carrageenan in rats. Mangiferin (150-1200 µg/paw), administered locally into the hindpaw, prevented hyperalgesia in a dose-dependent - 150 µg (- 9%), 300 µg (- 27%, P < 0.01), 600 µg (- 77%, P < 0.001) and 1000 µg (- 93%, P < 0.001) - and local manner. Mangiferin showed decreased levels of TNF-α (P < 0.001) and CINC-1 (P < 0.001), but not IL-1ß; it also prevented neutrophil migration (P < 0.01), but not the increased COX-2 expression in peripheral tissue challenged with carrageenan. To further explore the mechanisms of mangiferin actions, rats were injected with modulators of inflammation and nociception; mangiferin prevented hyperalgesia induced by IL-1ß (P < 0.01), CINC-1 (P < 0.01), epinephrine (P < 0.01), 8-Br-cAMP (P < 0.01) or capsaicin (P < 0.01), but not that induced by PGE2 or α,ß-MeATP. Our study shows that mangiferin has anti-inflammatory and analgesic properties when locally administrated. The control of the inflammatory response and mechanical hyperalgesia by mangiferin depends on the inhibition of TNF-α production/release and the CINC1/epinephrine/PKA pathway, supporting its marked inhibition of inflammatory mechanical hyperalgesia.

Synthetic chalcones as potential tool for acute- and chronic-pain control.

The purpose of this study was to validate the potential anti-hypersensitive activity of two chalcones, (2E)-1-(4-aminophenyl)-3-(4-nitrophenyl)prop-2-en-1-one (ANCh) and N-{4-[(2E)-3-(4-nitrophenyl)prop-2-enoil]phenyl}acetamide (AcANCh), by different models of acute and persistent pain in mice, besides in silico analysis. Molecules computational investigation for prediction of Lipinki's and Veber's rules to determine solubility, % absorption, drug likeness and toxicity liabilities was performed. Male and female C57BL/6 mice (20-30 g, n = 6) were used. Firstly, mice were pre-treated with the compounds ANCh or AcANCh and then submitted to the models of acute hypersensitivity by the intraplantar injection of different phlogistic agents. The mechanical sensitivity was assessed using von Frey hairs (0.6 g). The obtained data shows that both compounds presented important inhibitory effects on mechanical hypersensitivity induced by carrageenan (with oral bioavailability). The anti-hypersensitive effect was also accompanied by the interference in leukocyte migration, interleukin-1ß (IL-1ß) and tumour necrosis factor (TNF) levels reduction and by the absence of unspecific effects. Added to the in vivo results, the in silico analysis presented none violation in Lipinski's or Veber's rules, good probability to cell membrane permeability and oral bioavailability, positive values of drug likeness and few risk of computational toxicity. ANCh partially reduced the hypersensitivity induced by IL-1ß and TNF, epinephrine and prostaglandin E2 (PGE2). AcANCh had similar effect, except for the absent of inhibition in PGE2-injected mice. Both compounds were capable of reducing the mechanical hypersensitivity presented in all persistent models of hypersensitivity (inflammatory pain, chronic nerve constriction and cancer pain), with emphasis for ANCh. These results suggest that both chalcones could represent good strategies for the control of acute and chronic pain, without important side effects. ANCh seems to involve cell migration and cytokines production as the main mechanism, together with interference in PGE2 neuronal sensitization pathway. In vivo and in silico analyses reinforce the potential characteristics of the compounds to become future drugs.

Anti-hypersensitivity effects of the phthalimide derivative N-(4methyl-phenyl)-4-methylphthalimide in different pain models in mice.

The treatment of chronic pain remains a challenge for clinicians worldwide, independent of its pathogenesis. It motivates several studies attempting to discover strategies to treat the disease. The in silico analysis using molecular docking approach demonstrated that the phthalimide N-(4methyl-phenyl)-4-methylphthalimide (MPMPH-1) presented high affinity to adenylyl-cyclase enzyme (AC). It also prominently reduced the mechanical hypersensitivity of mice challenged by Forskolin, an AC activator. This effect lasted for up to 48h after Forskolin injection, presenting activity longer than MDL-12330A (AC inhibitor). MPMPH-1 was also effective in reducing the hypersensitivity induced by IL-1ß, bradykinin, prostaglandin E2 or epinephrine, chemical mediators that have, among others, AC as pivotal protein in their signalling cascade to induce mechanical-pain behaviour. The compound presented marked inhibition in inflammatory-pain models induced by carrageenan, lipopolysaccharide or complete Freund's adjuvant, including neutrophil migration inhibition. Furthermore, it also seems to act in both peripheral and pain central-control pathways, being also effective in reducing the persistent cancer-pain behaviour induced by melanoma cells in mice. MPMPH-1 could represent a promising pharmacological tool to treat acute and chronic painful diseases, with good bioavailability, local activity, and lack of locomotor-activity interference. Further studies are necessary to determine the exact mechanism of action but it seems to involve AC enzyme as possible target.

Ipomoea pes-caprae (L.) R. Br (Convolvulaceae) relieved nociception and inflammation in mice - A topical herbal medicine against effects due to cnidarian venom-skin contact.

ETHNOPHARMACOLOGICAL RELEVANCE: Ipomoea pes-caprae is known as bayhops, beach morning glory or goat's foot, and in Brazil as salsa-de-praia. Its leaves are used in worldwide folk medicine for the relief of jellyfish-stings symptoms. The literature only reports the neutralizing effects of nonpolar plant derived over jellyfish venoms, without validating the popular use or exploring the mechanism of action. AIM OF THE STUDY: This study aimed to evaluate and validate the topical effects of a semisolid containing hydroethanolic extract obtained from the aerial parts of I. pes-caprae using different models of paw- and ear-oedema and spontaneous nociception in mice, attempting to better understand the mechanism involved in its effect. MATERIALS AND METHODS: Leaf and stem of I. pes-caprae were extracted by ethanol 50% (v/v) and the soft-extract was incorporated in Hostacerin® cream base at 0.5%, 1.0% and 2% (w/w). The anti-hypersensitivity effects were evaluated by injecting the Physalia physalis venom into the right mice's hindpaw pre-treated either with the semisolid containing the I. pes-caprae extract or with the isolated majority compound 3,5-Di-O-caffeoylquinic acid (ISA). The topical anti-inflammatory activity was investigated using both preclinical models: paw oedema induced by trypsin, bradykinin (BK), histamine and carrageenan, and ear oedema induced by capsaicin. Additionally, the model of spontaneous nociception induced by trypsin and capsaicin were used to verify the topical antinociceptive activity. RESULTS: The animals pre-treated with the semisolid containing I. pes-caprae extract or with the intraplantar injection of the major component (ISA) had the mechanical hypersensitivity induced by P. physalis venom significantly reduced. Significant inhibition was also observed in paw-oedema induced by trypsin, histamine and BK, and in a less extent in carrageenan-induced paw oedema. Similar effect was observed in mice challenged to the capsaicin-induced ear-oedema. Besides the vascular effects, the extract interfered with leukocyte migration induced by histamine injection. Finally, the semisolid presented significant inhibition in trypsin- and capsaicin-induced spontaneous nociception. CONCLUSIONS: The hydroethanolic extract of I. pes-caprae showed compliance with the topical popular use of the herbal product to relieve the symptoms evoked by the cnidarian venom-skin contact, such as neurogenic oedema and nociception. The extract components seem to interfere with the effects resulting from the TRPV1, B2R and PAR-2 activation, once it interfered with painful-behaviour and oedema induced by capsaicin, BK and trypsin, pointing the histaminergic system as the main target, once it is an important mediator in the signalling pathway of the aforementioned receptors.

Topical anti-inflammatory phytomedicine based on Sphagneticola trilobata dried extracts.

CONTEXT: The aerial parts of Sphagneticola trilobata (L.) Pruski (Asteraceae) are popularly used to treat topical inflammation, but have not been fully investigated. OBJECTIVE: To identify polar compounds in S. trilobata extracts and develop a new topical phytomedicine based on the kaurenoic acid (KA) content while monitoring and demonstrating its topical anti-inflammatory activity. MATERIALS AND METHODS: Ethanol spray-dried extract of S. trilobata was analysed by LC-MS while the KA content from semisolid was analysed by LC-UV. The extent of ear edema induced by applying 20 µL of croton oil (2.5%), arachidonic acid (AA; 2 mg/ear) and decanoylphorbol-13-acetate (TPA; 2.5 mg/ear) in mice was used to evaluate the biological activity of the semisolids, which were applied 30 min before the phlogistic agents. RESULTS: Eight phenylpropanoids and four oleanane-type triterpenoid saponins were identified, majority of them reported for the first time in this species, in addition to KA. The semisolid containing 1.0% of dried extract reduced the ear edema induced by croton oil [77.2 ± 4.5%; ID50 = 0.49 (0.28-0.87%)], TPA (81.5 ± 2.4%) and AA (39.1 ± 6.9%), with decreasing effect at higher KA concentrations. This was accompanied by neutrophil migration inhibition as investigated by biochemical and histological assays. DISCUSSION AND CONCLUSION: The anti-inflammatory effects were (at least in part) due to the interference in protein kinase C (PKC) activation, AA-cascade products and neutrophil migration inhibition, demonstrating the efficacy of the folk topical usage of this plant. The results support the development of a novel topical anti-inflammatory phytomedicine properly standardized to treat inflammatory dermatological diseases.