A 9-aminoacridine derivative induces growth inhibition of Ehrlich ascites carcinoma cells and antinociceptive effect in mice.

Acridine derivatives have been found with anticancer and antinociceptive activities. Herein, we aimed to evaluate the toxicological, antitumor, and antinociceptive actions of N'-(6-chloro-2-methoxyacridin-9-yl)-2-cyanoacetohydrazide (ACS-AZ), a 9-aminoacridine derivative with antimalarial activity. The toxicity was assessed by acute toxicity and micronucleus tests in mice. The in vivo antitumor effect of ACS-AZ (12.5, 25, or 50 mg/kg, intraperitoneally, i.p.) was determined using the Ehrlich tumor model, and toxicity. The antinociceptive efficacy of the compound (50 mg/kg, i.p.) was investigated using formalin and hot plate assays in mice. The role of the opioid system was also investigated. In the acute toxicity test, the LD50 (lethal dose 50%) value was 500 mg/kg (i.p.), and no detectable genotoxic effect was observed. After a 7-day treatment, ACS-AZ significantly (p < 0.05) reduced tumor cell viability and peritumoral microvessels density, suggesting antiangiogenic action. In addition, ACS-AZ reduced (p < 0.05) IL-1ß and CCL-2 levels, which may be related to the antiangiogenic effect, while increasing (p < 0.05) TNF-α and IL-4 levels, which are related to its direct cytotoxicity. ACS-AZ also decreased (p < 0.05) oxidative stress and nitric oxide (NO) levels, both of which are crucial mediators in cancer known for their angiogenic action. Moreover, weak toxicological effects were recorded after a 7-day treatment (biochemical, hematological, and histological parameters). Concerning antinociceptive activity, ACS-AZ was effective on hotplate and formalin (early and late phases) tests (p < 0.05), characteristic of analgesic agents with central action. Through pretreatment with the non-selective (naloxone) and µ1-selective (naloxonazine) opioid antagonists, we observed that the antinociceptive effect of ACS-AZ is mediated mainly by µ1-opioid receptors (p < 0.05). In conclusion, ACS-AZ has low toxicity and antitumoral activity related to cytotoxic and antiangiogenic actions that involve the modulation of reactive oxygen species, NO, and cytokine levels, in addition to antinociceptive properties involving the opioid system.

Physical and mental health impacts during COVID-19 quarantine in adolescents with preexisting chronic immunocompromised conditions

Abstract Objective: To evaluate physical and mental health indicators in adolescents with preexisting chronic immunocompromised conditions during coronavirus disease 2019 (COVID-19) quarantine. Methods: A cross-sectional study included 355 adolescents with chronic conditions and 111 healthy adolescents. An online self-rated survey was used to investigate socio-demographic features, healthcare routine, and the quarantine impact on physical and mental health. The validated self-reported version of the Strengths and Difficulties Questionnaire (SDQ) was also applied. Results: The median of age [14 (10-18) vs. 15 (10-18) years, p = 0.733] and frequencies of female (61% vs. 60%, p = 0.970) were similar between adolescents with preexisting chronic conditions and healthy adolescents during quarantine of COVID-19 pandemic. The frequencies of abnormal total difficulties score of SDQ were similar in patients and controls (30% vs. 31%, p = 0.775). Logistic regression analysis showed that being female (OR = 1.965; 95% CI = 1.091-3.541, p = 0.024), fear of underlying disease activity/complication (OR = 1.009; 95%CI = 1.001-1.018, p = 0.030) were associated with severe psychosocial dysfunction in adolescents with chronic conditions, whereas school homework (OR = 0.449; 95% CI = 0.206-0.981, p = 0.045) and physical activity (OR = 0.990; 95% CI = 0.981-0.999, p = 0.030) were protective factors. Further analysis of patients with chronic immunocompromised conditions and previous diagnosis of mental disorders (9%) compared with patients without diagnosis showed higher median of total difficulties score (p = 0.001), emotional (p = 0.005), conduct (p = 0.007), peer problems (p = 0.001) and hyperactivity (p = 0.034) in the former group. Conclusion: Adolescents with preexisting chronic immunocompromised conditions during COVID-19 quarantine were not at higher risk of adverse health indicators. Being female, fear of underlying disease activity/complication, and household members working outside of the home were relevant issues for adolescents with preexisting chronic conditions. This study reinforces the need to establish mental health strategies for teens with chronic conditions, particularly during the pandemic.

EFFICACY OF METHOTREXATE MICROINFUSION IN SCALP LESIONS OF PATIENTS WITH FIBROSING FRONTAL ALOPECIA: A PROSPECTIVE CONTROLLED TRIAL / EFICÁCIA DA MICROINFUSÃO DE METOTREXATO EM LESÕES DO COURO DE PACIENTES COM ALOPECIA FIBROSANTE: ENSAIO CLÍNICO PROSPECTIVO CONTROLADO

Introdução: A alopecia frontal fibrosante (AFF) é uma cicatriz linfocítica, com queda de cabelo pela linha de implantação frontal do couro cabeludo e outras áreas do corpo. Drogas tópicas e sistêmicas, como casos o MTX, não controlam a atividade da doença na maioria dos casos, a necessidade de novas terapias. Objetivo: Avaliar a diligência da microinfusão de metotrexato em AFF. Métodos: Ensaio clínico prospectivo, controlador, realizado com 17 voluntários com 1 diagnóstico clínico e histológico de AFF. As aplicações de MTX por MMP® (método de microinfusão de pele) foram feitas a cada 30 dias, num total de 3 aplicações, na direita da área de alopecia; a outra metade serviu como controle.medidas frontais glalares e parciais, dermatoscópicas, índice de avaliação externa dos olhos, a percepção do plano dos sinais do paciente (LPPAI). Hemograma total e testes de função hepática também foram médios. Resultados: Houve uma redução significativa nas medidas fronto-glabela e frontal temporo-parietal no local tratado, enquanto no local nãou a AAF aumentou. A paciente refere melhora do prurido e descamação, mas não da queda de cabelo e eritema local. A das fotos dermatoscópicas e a análise do LPPAI não são relevantes. Cerca de 9 participantes e todos nós não resultaram em 5% dos resultados com nenhum resultado de nenhum dos exames.Conclusão: A aplicação de MTX por MMP® melhorou os sintomas associados à AFF e as medidas fronto-glabela e fronto-parietal.

Introdução: A alopecia frontal fibrosante (AFF) é cicatricial linfocítica, com queda de cabelo pela linha de implantação frontal do couro cabeludo e outras áreas do corpo. Drogas tópicas e sistêmicas, como o metotrexato (MTX), não controlam a atividade da doença na maioria dos casos, mostrando a necessidade de novas terapias. Objetivo: Avaliar a eficácia da microinfusão de metotrexato em AFF. Métodos: Ensaio clínico prospectivo, controlado, realizado com 17 voluntários com diagnóstico clínico e histológico de AFF. As aplicações de MTX por MMP® (método de microinfusão de drogas na pele) foram feitas a cada 30 dias, totalizando 3 aplicações, na metade direita da área da alopecia; a outra metade serviu como controle. Foram avaliadas as medidas frontoglabela e frontal temporoparietal. Fotos de dermatoscopia foram analisadas por avaliadores cegos e externos com percepção de sinais e sintomas do paciente e o Índice de Atividade do Líquen Planopilar (LPPAI). Hemograma total e testes de função hepática também foram medidos. Resultados: Houve redução significativa nas medidas frontoglabela e frontal temporoparietal no local tratado, enquanto no não tratado a AAF aumentou. Houve melhora do prurido e descamação, mas não da queda de cabelo e eritema local. A análise das fotos dermatoscópicas e o cálculo do LPPAI não mostraram alterações relevantes. Cerca de 95% dos participantes ficaram satisfeitos ou muito satisfeitos com os resultados e nenhum deles teve alteração nos resultados dos exames laboratoriais. Conclusão: A aplicação de MTX por MMP® melhorou os sintomas associados à AFF e as medidas frontoglabela e frontoparietal. Esta técnica mostrou-se segura e bem tolerada.

Hyperbaric oxygen therapy mitigates left ventricular remodeling, upregulates MMP-2 and VEGF, and inhibits the induction of MMP-9, TGF-ß1, and TNF-α in streptozotocin-induced diabetic rat heart.

AIMS: Hyperbaric oxygen (HBO) therapy has been widely used for the adjunctive treatment of diabetic wounds, and is currently known to influence left ventricular (LV) function. However, morphological and molecular repercussions of the HBO in the diabetic myocardium remain to be described. We aimed to investigate whether HBO therapy would mitigate adverse LV remodeling caused by streptozotocin (STZ)-induced diabetes. MAIN METHODS: Sixty-day-old Male Wistar rats were divided into four groups: Control (n = 8), HBO (n = 7), STZ (n = 10), and STZ + HBO (n = 8). Diabetes was induced by a single STZ injection (60 mg/kg, i.p.). HBO treatment (100% oxygen at 2.5 atmospheres absolute, 60 min/day, 5 days/week) lasted for 5 weeks. LV morphology was evaluated using histomorphometry. Gene expression analyzes were performed for LV collagens I (Col1a1) and III (Col3a1), matrix metalloproteinases 2 (Mmp2) and 9 (Mmp9), and transforming growth factor-ß1 (Tgfb1). The Immunoexpression of cardiac tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) were also quantified. KEY FINDINGS: HBO therapy prevented LV concentric remodeling, heterogeneous myocyte hypertrophy, and fibrosis in diabetic rats associated with attenuation of leukocyte infiltration. HBO therapy also increased Mmp2 gene expression, and inhibited the induction of Tgfb1 and Mmp9 mRNAs caused by diabetes, and normalized TNF-α and VEGF protein expression. SIGNIFICANCE: HBO therapy had protective effects for the LV structure in STZ-diabetic rats and ameliorated expression levels of genes involved in cardiac collagen turnover, as well as pro-inflammatory and pro-angiogenic signaling.

Physical and mental health impacts during COVID-19 quarantine in adolescents with preexisting chronic immunocompromised conditions.

OBJECTIVE: To evaluate physical and mental health indicators in adolescents with preexisting chronic immunocompromised conditions during coronavirus disease 2019 (COVID-19) quarantine. METHODS: A cross-sectional study included 355 adolescents with chronic conditions and 111 healthy adolescents. An online self-rated survey was used to investigate socio-demographic features, healthcare routine, and the quarantine impact on physical and mental health. The validated self-reported version of the Strengths and Difficulties Questionnaire (SDQ) was also applied. RESULTS: The median of age [14 (10-18) vs. 15 (10-18) years, p = 0.733] and frequencies of female (61% vs. 60%, p = 0.970) were similar between adolescents with preexisting chronic conditions and healthy adolescents during quarantine of COVID-19 pandemic. The frequencies of abnormal total difficulties score of SDQ were similar in patients and controls (30% vs. 31%, p = 0.775). Logistic regression analysis showed that being female (OR = 1.965; 95% CI = 1.091-3.541, p = 0.024), fear of underlying disease activity/complication (OR = 1.009; 95%CI = 1.001-1.018, p = 0.030) were associated with severe psychosocial dysfunction in adolescents with chronic conditions, whereas school homework (OR = 0.449; 95% CI = 0.206-0.981, p = 0.045) and physical activity (OR = 0.990; 95% CI = 0.981-0.999, p = 0.030) were protective factors. Further analysis of patients with chronic immunocompromised conditions and previous diagnosis of mental disorders (9%) compared with patients without diagnosis showed higher median of total difficulties score (p = 0.001), emotional (p = 0.005), conduct (p = 0.007), peer problems (p = 0.001) and hyperactivity (p = 0.034) in the former group. CONCLUSION: Adolescents with preexisting chronic immunocompromised conditions during COVID-19 quarantine were not at higher risk of adverse health indicators. Being female, fear of underlying disease activity/complication, and household members working outside of the home were relevant issues for adolescents with preexisting chronic conditions. This study reinforces the need to establish mental health strategies for teens with chronic conditions, particularly during the pandemic.

Poor Sleep quality and health-related quality of life impact in adolescents with and without chronic immunosuppressive conditions during COVID-19 quarantine.

OBJECTIVE: To assess the possible factors that influence sleep quality in adolescents with and without chronic immunosuppressive conditions quarantined during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This cross-sectional study included 305 adolescents with chronic immunocompromised conditions and 82 healthy adolescents. Online surveys were completed, which included questions on socio-demographic data and self-rated healthcare routine during COVID-19 quarantine and the following validated questionnaires: the Pittsburgh Sleep Quality Index (PSQI), Pediatric Quality of Life Inventory 4.0 (PedsQL4.0), and Pediatric Outcome Data Collection Instrument (PODCI). RESULTS: The median current age [14 (10-18) vs. 15 (10-18) years, p=0.847] and frequency of female sex (62% vs. 58%, p=0.571) were similar in adolescents with chronic conditions compared with healthy adolescents. The frequency of poor sleep quality was similar in both groups (38% vs. 48%, p=0.118). Logistic regression analysis, including both healthy adolescents and adolescents with chronic conditions (n=387), demonstrated that self-reported increase in screen time (odds ratio [OR] 3.0; 95% confidence interval [CI] 1.3-6.8; p=0.008) and intrafamilial violence report (OR 2.1; 95% CI 1.2-3.5; p=0.008) were independently associated with poor sleep quality in these adolescents. However, the PODCI global function score was associated with a lower OR for poor sleep quality (OR 0.97; 95% CI 0.94-0.99; p=0.001). Further logistic regression, including only adolescents with chronic conditions (n=305), demonstrated that self-reported increase in screen time (OR 3.1; 95% CI 1.4-6.8; p=0.006) and intrafamilial violence report (OR 2.0; 95% CI 1.2-3.4; p=0.011) remained independently associated with poor quality of sleep, whereas a lower PODCI global function score was associated with a lower OR for sleep quality (OR 0.96; 95% CI 0.94-0.98; p<0.001). CONCLUSION: Self-reported increases in screen time and intrafamilial violence report impacted sleep quality in both healthy adolescents and those with chronic conditions. Decreased health-related quality of life was observed in adolescents with poor sleep quality.

S-methyl cysteine sulfoxide mitigates histopathological damage, alleviate oxidative stress and promotes immunomodulation in diabetic rats.

OBJECTIVES: S-methyl cysteine sulfoxide (SMCS) is a hydrophilic cysteine-containing natural compound found in plants and is known to possess antidiabetic and antioxidant properties. We investigated the antioxidant and immunomodulatory properties of SMCS, as well as histopathological changes in the liver and pancreas in streptozotocin (STZ)-induced diabetic rats. METHODS: The rats were divided into the following groups: control (CG), comprising non-diabetic rats; STZ-DB, comprising STZ-induced diabetic rats; and STZ-SMCS, comprising STZ-induced diabetic rats treated with SMCS. SMCS (200 mg/kg) was administered by gavage daily for 30 days. Biochemical and cytokine analyses, catalase (CAT) and superoxide dismutase (SOD) activities assays and histopathological analysis of liver and pancreas tissues were performed. RESULTS: SMCS treatment reduced glycemia (p<0.05), decreased triglyceride (p<0.01) and very-low-density lipoprotein (VLDL) levels (p<0.01), and increased SOD and CAT activity in the liver (both p<0.01) compared with STZ-DB group. Higher activity values of IL-10 were observed in the STZ-SMCS group than in the other groups (p<0.001). Liver glycogen was significantly improved in the STZ-SMCS group compared with the STZ-DB group. SMCS also ameliorated damage to pancreatic islets, which resulted in restoration of their morphology. CONCLUSIONS: Oral treatment of SMCS showed improvement of the morphological alterations in liver and pancreatic islet in diabetic rats. These beneficial morphological effects of SMCS can be partially explained by IL-10 modulation associated with antioxidant action.

S-methyl cysteine sulfoxide ameliorates duodenal morphological alterations in streptozotocin-induced diabetic rats.

Diabetes mellitus (DM) is a metabolic disease associated with several intestinal disorders. S-methyl cysteine sulfoxide (SMCS) ​​is an amino acid present in Allium cepa L with hypoglycemic effects. However, the effects of SMCS on diabetic intestinal changes are unknown. Thus, we aimed to investigate the effects of SMCS on duodenal morphology and immunomodulatory markers in diabetic rats. Twenty-six rats were divided into three groups: control (C), diabetic (D) and diabetic +200 mg/kg SMCS (DSM). DM was induced by intraperitoneal injection of streptozotocin (50 mg/kg). After 30 days, duodenum samples were processed to assess histopathological and stereological alterations in volume, villus length, and immunohistochemical expression of NF-kB, IL-10, BCL-2, and caspase-3. SMCS reduced hyperglycemia and mitigated the increase in total reference volume of the duodenum, the absolute volume of the mucosa, and the length of the intestinal crypts in the DMS group when compared to D. IL-10 immunostaining was reduced in D when compared to C, while NF-kB was increased in D in comparison to the other groups. SMCS ​​supplementation could decrease the NF-kB immunostaining observed in D. Positive staining for BCL-2 and caspase-3 were not statistically different between groups. In summary, SMCS decreased hyperglycemia and mitigated the morphological changes of the duodenum in diabetic animals, and these beneficial effects can be partially explained by NF-kB modulation.

Epidemiology and Etiopathogeny of COVID-19.

Despite the recent announcement of the new pathogenic coronavirus to man, SARS-CoV2, a large number of publications are presented to the scientific community. An organized and systematic review of the epidemiological, etiological, and pathogenic factors of COVID-19 is presented. This is a systematic review using the databases MEDLINE, EMBASE, Web of Science, SCIELO; the descriptors coronavirus, SARS-CoV-2, etiology, epidemiology, pathophysiology, pathogenesis, COVID-19, with publications from December 2019 to January 2021, resulting in more than 800 publications and 210 selected. The data suggest that COVID-19 is associated with SAR-CoV-2 infection, with the transmission of contagion by fomites, salivary droplets, and other forms, such as vertical and fecal-oral. The bat and other vertebrates appear to be reservoirs and part of the transmission chain. The virus uses cell receptors to infect human cells, especially ACE2, like other coronaviruses. Heat shock proteins have different roles in the infection, sometimes facilitating it, sometimes participating in more severe conditions, when not serving as a therapeutic target. The available data allow us to conclude that COVID-19 is a pandemic viral disease, behaving as a challenge for public health worldwide, determining aggressive conditions with a high mortality rate in patients with risk factors, without treatment, but with the recent availability of the first vaccines.

Anatomopathological Aspects and Clinical Correlation of COVID-19: A Systematic Review.

OBJECTIVE: The objective of this systematic review was to analyze the main morphofunctional changes in the involvement of multiple organs in patients infected with SARS-CoV-2, correlating anatomopathological findings with the clinical picture. METHODS: The present study selected articles through electronic search of indexed journals in the PubMed and SciVerse Scopus databases, from December 2019 to May 2020, using the keywords "autopsy," "pathogenicity," and "COVID-19." Two hundred nine articles were identified, and the full texts of 18 articles were reviewed, 5 of them being selected for this review. RESULTS: The ACE2 receptor plays a role in introducing viral material into the cell, having high expression in type II alveoli. Histopathological analyzes of the lungs of patients with COVID-19 show that SARS-CoV-2 produces, in this organ, in addition to an inflammatory process, a diffuse alveolar damage (DAD), which can cause acute respiratory distress syndrome (ARDS). Macroscopically, the lungs become heavier, firmer, and redder. The clinical features of these patients are variable; the most common are respiratory symptoms associated with fever, myalgia, or fatigue. CONCLUSION: The observations points to the consensus that the lungs are the main targets of COVID-19, with morphological and functional changes of interest, including important sequels, and presenting diffuse alveolar damage as a substrate for an unfavorable outcome with ARDS. Changes in micro and macroscopic levels corroborate to the clinical progression of the disease and that these alterations are not specific, which ratify, in addition to the anatomopathological examination, a need to use the association of clinical and epidemiological data for diagnostic confirmation.

Poor Sleep quality and health-related quality of life impact in adolescents with and without chronic immunosuppressive conditions during COVID-19 quarantine

OBJECTIVE: To assess the possible factors that influence sleep quality in adolescents with and without chronic immunosuppressive conditions quarantined during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This cross-sectional study included 305 adolescents with chronic immunocompromised conditions and 82 healthy adolescents. Online surveys were completed, which included questions on socio-demographic data and self-rated healthcare routine during COVID-19 quarantine and the following validated questionnaires: the Pittsburgh Sleep Quality Index (PSQI), Pediatric Quality of Life Inventory 4.0 (PedsQL4.0), and Pediatric Outcome Data Collection Instrument (PODCI). RESULTS: The median current age [14 (10-18) vs. 15 (10-18) years, p=0.847] and frequency of female sex (62% vs. 58%, p=0.571) were similar in adolescents with chronic conditions compared with healthy adolescents. The frequency of poor sleep quality was similar in both groups (38% vs. 48%, p=0.118). Logistic regression analysis, including both healthy adolescents and adolescents with chronic conditions (n=387), demonstrated that self-reported increase in screen time (odds ratio [OR] 3.0; 95% confidence interval [CI] 1.3-6.8; p=0.008) and intrafamilial violence report (OR 2.1; 95% CI 1.2-3.5; p=0.008) were independently associated with poor sleep quality in these adolescents. However, the PODCI global function score was associated with a lower OR for poor sleep quality (OR 0.97; 95% CI 0.94-0.99; p=0.001). Further logistic regression, including only adolescents with chronic conditions (n=305), demonstrated that self-reported increase in screen time (OR 3.1; 95% CI 1.4-6.8; p=0.006) and intrafamilial violence report (OR 2.0; 95% CI 1.2-3.4; p=0.011) remained independently associated with poor quality of sleep, whereas a lower PODCI global function score was associated with a lower OR for sleep quality (OR 0.96; 95% CI 0.94-0.98; p<0.001). CONCLUSION: Self-reported increases in screen time and intrafamilial violence report impacted sleep quality in both healthy adolescents and those with chronic conditions. Decreased health-related quality of life was observed in adolescents with poor sleep quality.

Carvone Enantiomers Differentially Modulate IgE-Mediated Airway Inflammation in Mice.

Carvone is a monoterpene found in nature in the form of enantiomers (S- and R-). While previous research has demonstrated the anti-inflammatory and anti-allergic effects of carvone, the influence of carvone enantiomeric composition on its anti-allergic activity remains to be investigated. This study aimed to evaluate the anti-allergic activity of carvone enantiomers in a murine model of airway allergic inflammation induced by sensitization and challenge with ovalbumin (OVA). The oral treatment with R-carvone or S-carvone 1 h before each challenge inhibited the number of leukocytes and eosinophils in the bronchoalveolar lavage (BAL). R-carvone inhibited leukocyte infiltration and mucus production in the lung, which was correlated with decreased production of OVA-specific IgE in the serum and increased concentrations of IL-10 in the BAL. On the other hand, the administration of S-carvone had little inhibitory effect on inflammatory infiltration and mucus production in the lung, which might be associated with increased production of IFN-γ in the BAL. When administered 1 h before each sensitization, both enantiomers inhibited eosinophil recruitment to the BAL but failed in decreasing the titers of IgE in the serum of allergic mice. Our data indicate that carvone enantiomers differentially modulated IgE-mediated airway inflammation in mice. In conclusion, unlike S-carvone, R-carvone has the potential to be used in anti-allergic drug development.

Carcinoma basocelular na face de adolescente não sindrômico: de raridade para uma nova realidade? / Basal Cell Carcinoma in the Face of Non-Syndromic Adolescents: From Rarity to a New Reality?

O aumento na incidência do carcinoma basocelular (CBC) atinge todas as faixas etárias, incluindo jovens abaixo dos 20 anos. Por ser pouco lembrado nesse grupo de pacientes, o atraso no diagnóstico e o tratamento tardio da neoplasia podem ser mais comuns. Assim como para outras faixas etárias, a exposição excessiva à radiação ultravioleta é o principal fator de risco associado, porém fatores genéticos também podem estar envolvidos nos casos não sindrômicos. Descreve-se um caso de CBC na face de um adolescente, tratado com cirurgia micrográfica de Mohs

The increase in the incidence of basal cell carcinoma (BCC) affects all age groups, including young patients under twenty years old. Because it is poorly remembered in this group of patients, late diagnosis and treatment of this neoplasia may be more common. Like other age groups, excessive exposure to ultraviolet radiation is the main associated risk factor; however, genetic factors may also be involved in non-syndromic cases. We report a case of BCC on the face of an adolescent treated with Mohs micrographic surgery

Anticancer Effect of a Spiro-acridine Compound Involves Immunomodulatory and Anti-angiogenic Actions.

BACKGROUND/AIM: Studies with acridine compounds have reported anticancer effects. Herein, we evaluated the toxicity and antitumor effect of the (E)-1'-((4-chlorobenzylidene)amino)-5'-oxo-1',5'-dihydro-10H-spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-06), a promising anticancer spiro-acridine compound. MATERIALS AND METHODS: The toxicity of AMTAC-06 was evaluated on zebrafish and mice. Antitumor activity was assessed in Ehrlich ascites carcinoma model. Effects on angiogenesis, cytokine levels and cell cycle were also investigated. RESULTS: AMTAC-06 did not induce toxicity on zebrafish and mice (LD50 approximately 5000 mg/kg, intraperitoneally). No genotoxicity was observed on micronucleus assay. AMTAC-06 significantly reduced the total viable Ehrlich tumor cells and increased sub-G1 peak, suggesting apoptosis was triggered. Moreover, the compound significantly decreased the density of peritumoral microvessels, indicating an anti-angiogenic action, possibly dependent on the cytokine modulation (TNF-α, IL-1ß and IFN-γ). No significant toxicological effects were recorded for AMTAC-06 on tumor transplanted animals. CONCLUSION: AMTAC-06 has low toxicity and a significant antitumor activity.

A novel piperine analogue exerts in vivo antitumor effect by inducing oxidative, antiangiogenic and immunomodulatory actions.

Structural diversity characterizes natural products as prototypes for design of lead compounds. The aim of this study was to synthetize, and to evaluate the toxicity and antitumor action of a new piperine analogue, the butyl 4-(4-nitrobenzoate)-piperinoate (DE-07). Toxicity was evaluated against zebrafish, and in mice (acute and micronucleus assays). To evaluate the DE-07 antitumor activity Ehrlich ascites carcinoma model was used in mice. Angiogenesis, Reactive Oxygen Species (ROS) production and cytokines levels were investigated. Ninety-six hours exposure to DE-07 did not cause morphological or developmental changes in zebrafish embryos and larvae, with estimated LC50 (lethal concentration 50%) higher than 100 µg/mL. On the acute toxicity assay in mice, LD50 (lethal dose 50%) was estimated at around 1000 mg/kg, intraperitoneally (i.p.). DE-07 (300 mg/kg, i.p.) did not induce increase in the number of micronucleated erythrocytes in mice, suggesting no genotoxicity. On Ehrlich tumor model, DE-07 (12.5, 25 or 50 mg/kg, i.p.) induced a significant decrease on cell viability. In addition, there was an increase on ROS production and a decrease in peritumoral microvessels density. Moreover, DE-07 induced an increase of cytokines levels involved in oxidative stress and antiangiogenic effect (IL-1ß, TNF-α and IL-4). No significant clinical toxicological effects were recorded in Ehrlich tumor transplanted animals. These data provide evidence that DE-07 presents low toxicity, and antitumor effect via oxidative and antiangiogenic actions by inducing modulation of inflammatory response in the tumor microenvironment.

Tratamento de necrobiose lipoídica no antebraço esquerdo com associação entre luz intensa pulsada e laser Erbium-YAG 2940nm / Treatment of Necrobiosis Lipoidica in the left forearm with association of Intense Pulsed Light and Erbium-Yag Laser 2940nm

A necrobiose lipoídica (NL) é uma dermatose granulomatosa, que acomete principalmente diabéticos devido à degeneração do colágeno. Embora existam diferentes tratamentos, todos apresentam pouca resposta. Dentre as opções, a luz intensa pulsada (LIP) e o laser Erbium-YAG permitem aumentar a produção e remodelamento do colágeno tratando a atrofia, além de diminuir o eritema pela coagulação de vasos sanguíneos. Relata-se caso de mulher, 24 anos, com diabetes mellitus tipo I, submetida a tratamento de NL no antebraço esquerdo em sete sessões com a associação entre LIP e laser Erbium-YAG 2940nm. Observou-se melhora da atrofia central e do eritema.

Necrobiosis Lipoidica (NL) is a granulomatous dermatosis, mainly affecting people with diabetes due to collagen degeneration. Although there are different treatments, all have little response. Among the options, the Intense Pulsed Light (IPL) and the Laser Erbium-YAG enhance the production and remodeling of the collagen treating the atrophy, besides reducing the erythema by the coagulation of blood vessels. We report a case of a 24-year-old woman with type I Diabetes Mellitus who underwent NL treatment on her left forearm in seven sessions with the association of IPL and 2940 nm Erbium-YAG laser. We observed improvement in central atrophy and erythema

Associação de luz intensa pulsada e laser Erbium: Yag 2940nm para tratamento de lentigo na face / Association of intense pulsed light and Erbium: Yag 2940 nm laser for treatment of lentigo on the face

O lentigo solar está presente em 90% da população com mais de 50 anos de idade, apresentando-se como manchas hipercrômicas em regiões fotoexpostas, que aumentam com o envelhecimento e são mais frequentes em peles claras. Há diversas modalidades terapêuticas com melhores resultados quando associadas. Descrevemos o caso de um homem de 62 anos, fototipo II de Fitzpatrick, com queixa de máculas acastanhadas em dorso nasal há oito anos. Foi submetido à biópsia de pele, e o estudo histológico confirmou ser lentigo solar. O paciente foi tratado com seis sessões de luz intensa pulsada associada a laser de Erbium: YAG 2940nm, com bom resultado clínico

Solar lentigo is present in 90% of the population over 50 years of age andcharacterizes as hyperchromic spots in photoexposed regions. It increases with aging and is more frequent in light skin. There are several therapeutic modalities, which achieve better results whenassociated. We describe the case of a 62-year-old man with Fitzpatrick skinphototype II, complaining of brownish macules in nasal dorsum for eight years. The patient underwent a skin biopsy, and the histological study confirmed solar lentigo. The patient was treated with six sessions of Intense Pulsed Light associated with Erbium-Yag2940 nm Laser with a good clinical result

O papel do uso de tecnologias combinadas na abordagem de uma paciente com microstomia / The role of the use of combined technologies in the approach to a patient with microstomia

A microstomia ocorre em 70% dos pacientes com esclerose sistêmica e há poucas opções terapêuticas. Descrevemos caso de mulher de 39 anos com diagnóstico de esclerose sistêmica em 2010, em uso de micofenolato de mofetil e rituximabe, apresentando microstomia. Foram realizadas duas sessões de luz intensa pulsada e sete sessões de laser fracionado ablativo Erbium:YAG de 2940nm, com resposta clínica importante. A formação e reorganização de fibras colágenas e elásticas foram responsáveis pela melhora da microstomia. Há poucos estudos com o uso de tecnologias para a abordagem da microstomia. Este é o primeiro com Er:YAG 2940nm para esta finalidade

Facial surgeries are often challenging for surgeons due to their complex anatomy, aesthetic and functional importance. Interventions in the cosmetic subunit that comprises the eyebrows can be particularly difficult. This case report aims to demonstrate the use of island flap in this region. We performed the excision of melanocytic nevus, with a good outcome and absence of postoperative complications. This technique is commonly used for facial reconstruction; however, the literature describes only a few cases using this method for eyebrow reconstruction.

Antitumor Effect of a Novel Spiro-Acridine Compound is Associated with Up-Regulation of Th1-Type Responses and Antiangiogenic Action.

Tumor cells have specific features, including angiogenesis induction, cell cycle dysregulation, and immune destruction evasion. By inducing a T helper type 2 (Th2) immune response, tumor cells may favor immune tolerance within the tumor, which allows progression of cancer growth. Drugs with potential antitumor activity are the spiro-acridines, which is a promising new class of acridine compounds. Herein, the novel spiro-acridine (E)-5'-oxo-1'-((3,4,5-trimethoxybenzylidene)amino)-1',5'-dihydro-10H-spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-17) was synthesized and tested for antitumor effects. Toxicity evaluation was performed in mice after acute treatment (2000 mg/kg, intraperitoneally, i.p.). The Ehrlich ascites carcinoma model was used to investigate the antitumor activity of AMTAC-17 (12.5, 25, or 50 mg/kg, i.p.) after seven days of treatment. Effects on the cell cycle, angiogenesis, and inflammatory responses were investigated. LD50 (lethal dose 50%) was estimated to be higher than 5000 mg/kg. AMTAC-17 reduced the Ehrlich tumor's total viable cancer cells count and peritumoral micro-vessels density, and induced an increase in the sub-G1 peak. Additionally, there was an increase of Th1 cytokine profile levels (IL-1ß, TNF-α, and IL-12). In conclusion, the spiro-acridine compound AMTAC-17 presents low toxicity, and its in vivo antitumor effect involves modulation of the immune system to a cytotoxic Th1 profile and a reduction of tumor angiogenesis.

Toxicity and Antitumor Activity of a Thiophene-Acridine Hybrid.

The antitumor effects of thiophene and acridine compounds have been described; however, the clinical usefulness of these compounds is limited due to the risk of high toxicity and drug resistance. The strategy of molecular hybridization presents the opportunity to develop new drugs which may display better target affinity and less serious side effects. Herein, 2-((6-Chloro-2-methoxy-acridin-9-yl)amino)-5,6,7,8-tetrahydro-4H-cyclohepta[b]-thiophene-3-carbonitrile (ACS03), a hybrid thiophene-acridine compound with antileishmanial activity, was tested for toxicity and antitumor activity. The toxicity was evaluated in vitro (on HaCat and peripheral blood mononuclear cells) and in vivo (zebrafish embryos and acute toxicity in mice). Antitumor activity was also assessed in vitro in HCT-116 (human colon carcinoma cell line), K562 (chronic myeloid leukemic cell line), HL-60 (human promyelocytic leukemia cell line), HeLa (human cervical cancer cell line), and MCF-7 (breast cancer cell line) and in vivo (Ehrlich ascites carcinoma model). ACS03 exhibited selectivity toward HCT-116 cells (Half maximal inhibitory concentration, IC50 = 23.11 ± 1.03 µM). In zebrafish embryos, ACS03 induced an increase in lactate dehydrogenase, glutathione S-transferase, and acetylcholinesterase activities. The LD50 (lethal dose 50%) value in mice was estimated to be higher than 5000 mg/kg (intraperitoneally). In vivo, ACS03 (12.5 mg/kg) induced a significant reduction in tumor volume and cell viability. In vivo antitumor activity was associated with the nitric oxide cytotoxic effect. In conclusion, significant antitumor activity and weak toxicity were recorded for this hybrid compound, characterizing it as a potential anticancer compound.