Macroporous latex biomembrane from Hancornia speciosa modulates the inflammatory process and has a debridement effect on wound healing in rats.

PURPOSE: The angiogenic, osteogenic and anti-inflammatory activity of latex of Hancornia speciosa has been evidenced and indicates pharmacological potential with great applicability in the health area, especially in the wound healing process. The present work aimed to compare the effects of the H. speciosa macroporous latex biomembrane with saline on wound healing. METHODS: Forty-three Wistar rats were submitted to excisional wound induction procedure and divided into groups according to treatment: saline (G1), and macroporous biomembrane (G2). The animals were euthanized at three, seven, 14, and 21 days after injury induction (DAI), and three animals were used for the debridement test. Morphometric, macroscopic, and microscopic analyses of general pathological processes were performed. RESULTS: The macroporous biomembrane minimized necrosis and inflammation during the inflammatory and proliferative phases of the healing process, confirmed by the lower intensity of the crust and the debridement effect. In addition, the wounds treated with the macroporous biomembrane presented greater contraction rates in all the experimental periods analyzed. CONCLUSIONS: The macroporous biomembrane presents angiogenic, anti-inflammatory and debridement effects, contributing to the healing process, and can be considered a potentially promising new biomaterial to be used as a dressing.

The effect of bevacizumab, 5-fluorouracil, and triamcinolone on the healing modulation of surgical wounds in rats.

In this study, we aimed to analyze the effect of 5-fluorouracil, triamcinolone, and bevacizumab on scar modulation in an experimental rat model of surgical lesions. Rats (Rattus norvegicus albinus) were divided into four groups: bevacizumab, 5-fluorouracil + triamcinolone, bevacizumab + 5-fluorouracil + triamcinolone, and control (received no medication) groups. A linear, dorsal incision was created and sutured for the first intention wound healing, mimicking the surgical incision of upper blepharoplasty. Treatments were initiated on day 7, and the rats were euthanized on day 14. Only in the 5-fluorouracil + triamcinolone group was there a difference in the number of infiltrated monocytes. There was 56%, 86%, and 85% decrease in the number of neovessels in the bevacizumab, 5-fluorouracil + triamcinolone, and bevacizumab + 5-fluorouracil + triamcinolone groups, respectively, compared with the control. Picrosirius red staining showed higher collagen density and more organized collagen in the treatment groups than in the control group. Scar modulation was observed in all groups, but the 5-fluorouracil + triamcinolone group presented the best results. To our knowledge, this is the first study to evaluate the influence of three medications in combination on healing. When used together, these medications can prevent the development of unsightly scars, and are therefore promising alternatives to corticosteroids.

Macroporous latex biomembrane from Hancornia speciosa modulates the inflammatory process and has a debridement effect on wound healing in rats

Purpose: The angiogenic, osteogenic and anti-inflammatory activity of latex of Hancornia speciosa has been evidenced and indicates pharmacological potential with great applicability in the health area, especially in the wound healing process. The present work aimed to compare the effects of the H. speciosa macroporous latex biomembrane with saline on wound healing. Methods: Forty-three Wistar rats were submitted to excisional wound induction procedure and divided into groups according to treatment: saline (G1), and macroporous biomembrane (G2). The animals were euthanized at three, seven, 14, and 21 days after injury induction (DAI), and three animals were used for the debridement test. Morphometric, macroscopic, and microscopic analyses of general pathological processes were performed. Results: The macroporous biomembrane minimized necrosis and inflammation during the inflammatory and proliferative phases of the healing process, confirmed by the lower intensity of the crust and the debridement effect. In addition, the wounds treated with the macroporous biomembrane presented greater contraction rates in all the experimental periods analyzed. Conclusions: The macroporous biomembrane presents angiogenic, anti-inflammatory and debridement effects, contributing to the healing process, and can be considered a potentially promising new biomaterial to be used as a dressing.

Tissue healing changes on wounds in rats after treatment with Hancornia speciosa latex in cream-gel formulation.

PURPOSE: Hancornia speciosa latex has shown pharmacological potential in wound healing processes due to its angiogenic, osteogenic, and anti-inflammatory activities. The aims of this study were to carry out a cream-gel formulation with 5, 10 and 25% of H. speciosa serum latex and to evaluate its potential to stimulate the skin regeneration in rats' wounds. METHODS: One hundred and twenty rats were divided into five groups: neutral control with saline (G1), cream-gel based on H. speciosa latex serum at 5% m/v (G2), cream-gel at 15% m/v (G3), cream-gel at 25% m/v (G4), and cream-gel (G5). The animals were euthanized at three, seven, 14 and 21 days after the injury induction, and some parameters were analyzed: wound contraction, necrosis, fibrin, polymorphonuclear and mononuclear infiltrates, fibroblast, angiogenesis, hemorrhage, and collagen. RESULTS: The therapeutic treatment with cream-gel at 15 and 25% is beneficial in the inflammatory phase of healing processes since it increased the angiogenesis and proliferation of mononuclear infiltrations in wounds. Regarding wound contraction, the treatment with cream-gel (5 and 15%) induced a higher rate of contraction in the proliferative phase. The 15% cream-gel formulation stimulated a greater production of collagen in the injured tissues. CONCLUSIONS: H. speciosa cream-gel is a low-cost herbal medicine which can aid in tissue repair.

Treatment of experimentally induced partial-thickness burns in rats with different silver-impregnated dressings.

PURPOSE: To evaluate the morphometric, macroscopic and microscopic aspects of experimentally induced partial-thickness burns in rats treated with different silver-based dressings. METHODS: Wistar rats were used, divided into six treatments: saline (NaCl 0.9%); silver sulfadiazine 1%; Silvercel; Mepilex Ag; Aquacel Ag and Acticoat. The animals were monitored daily and euthanized at 7, 14 and 30 days after injury induction (DAI). RESULTS: At 7 DAI, necrosis/crust was greater in control, silver sulfadiazine and Mepilex Ag treatments, granulation tissue was induced by Aquacel Ag, polymorphonuclear infiltrate (PMN) infiltration was intensified by Mepilex Ag; mononuclear infiltrate (MN) infiltration and angiogenesis were increased by Silvercel. At 14 DAI, hemorrhage was decreased by Silvercel and Mepilex Ag, PMN infiltration increased by Acticoat. At 30 DAI, angiogenesis was greater in the Acticoat treatment and fibroblasts were increased by Acticoat and Mepilex Ag. Collagen was induced at 14 DAI by silver sulfadiazine and Aquacel Ag and, at 30 DAI, by silver sulfadiazine and Silvercel treatments. CONCLUSIONS: Silvercel and Acticoat presented better results than the other products. However, all the dressings were better than the control at some point during the process, and may contribute to the healing of partial thickness burns. Silvercel and Aquacel Ag treatments induced better cosmetic outcomes regarding wound closure and scarring.

Hydrogel-based dressings in the treatment of partial thickness experimentally induced burn wounds in rats.

PURPOSE: To compare four commercially available hydrogel formulations in the healing of partial thickness burns experimentally induced in rats. METHODS: Wistar rats were used, and after the burn wound induction they were divided into the following treatment groups: G1) NaCl 0.9%; G2) 1% silver sulfadiazine; G3) Debrigel™; G4) Safgel™; G5) Dersani™; G6) Solosite™. The animals were followed during seven, 14 and 30 days after the injury induction. Morphometric, macroscopic and microscopic evaluations were performed. RESULTS: The treatment with Dersani™ induced better results during the inflammatory and proliferative phases of the healing process (p<0.05). The animals treated with Safgel™ presented better scaring in the remodeling phase (p<0.05), and the treatment with Dersani™ and Solosite™ induced greater wound closure (p<0.05). CONCLUSIONS: The hydrogel-based dressings presented beneficial outcomes in the healing of burn wounds experimentally induced in rats due to their ability in maintain the humidity of the wound, in removing the exudate, in promoting cell migration and collagen production during the different phases of the healing process.

The role of enzymes in the angiogenic activity of Hancornia speciosa latex

The Hancornia speciosa latex has shown angiogenic activity. Angiogenesis plays a major role in wound healing, and materials that stimulate this process could be used to develop drugs. This study aimed to explain the role of proteins in the H. speciosa serum fraction latex in angiogenesis. Hence, this material was treated with proteinase K and the proteins were inactivated. After protein inactivation, angiogenic activity was assessed with the chick chorioallantoic membrane assay. The result showed that the proteins in the serum fraction are responsible for angiogenic activity. Then, the total protein content in the serum fraction and its enzymatic activity were investigated. The low protein content observed in the H. speciosa serum fraction latex suggests that this biomaterial could be used to develop new drugs with a hypoallergenic response. Despite the low protein content, there was a significant enzymatic activity of at least three enzymes in the serum fraction latex: ß-1,3 glucanase, ß-glucosidase, and proteases. These enzymes seem to influence the healing process, assisting debridement, extracellular matrix remodeling, and collagen deposition, and decreasing the chances of contamination by microorganisms. In conclusion, the enzymes in the H. speciosa serum latex are associated with the angiogenic activity of this biomaterial and may be used to assist the wound healing process.

Treatment of experimentally induced partial-thickness burns in rats with different silver-impregnated dressings

Purpose: To evaluate the morphometric, macroscopic and microscopic aspects of experimentally induced partial-thickness burns in rats treated with different silver-based dressings. Methods: Wistar rats were used, divided into six treatments: saline (NaCl 0.9%); silver sulfadiazine 1%; Silvercel; Mepilex Ag; Aquacel Ag and Acticoat. The animals were monitored daily and euthanized at 7, 14 and 30 days after injury induction (DAI). Results: At 7 DAI, necrosis/crust was greater in control, silver sulfadiazine and Mepilex Ag treatments, granulation tissue was induced by Aquacel Ag, polymorphonuclear infiltrate (PMN) infiltration was intensified by Mepilex Ag; mononuclear infiltrate (MN) infiltration and angiogenesis were increased by Silvercel. At 14 DAI, hemorrhage was decreased by Silvercel and Mepilex Ag, PMN infiltration increased by Acticoat. At 30 DAI, angiogenesis was greater in the Acticoat treatment and fibroblasts were increased by Acticoat and Mepilex Ag. Collagen was induced at 14 DAI by silver sulfadiazine and Aquacel Ag and, at 30 DAI, by silver sulfadiazine and Silvercel treatments. Conclusions: Silvercel and Acticoat presented better results than the other products. However, all the dressings were better than the control at some point during the process, and may contribute to the healing of partial thickness burns. Silvercel and Aquacel Ag treatments induced better cosmetic outcomes regarding wound closure and scarring.

Carboxymethyl chitosan hydrogel formulations enhance the healing process in experimental partial-thickness (second-degree) burn wound healing.

PURPOSE: This study aimed to elaborate a hydrogel constituted by carboxymethyl chitosan (CMC), hyaluronic acid (HA) and silver (Ag) and to evaluate its healing effect on partial-thickness burn wounds experimentally induced in rats. METHODS: CMC was obtained by chitosan reacting with monochloroacetic acid. The carboxymethylation was confirmed by Fourier-transform infrared spectroscopy and hydrogen nuclear magnetic resonance (NMR). Scanning electron microscopy was used to determine the morphologicalcharacteristics of chitosan and CMC. After the experimental burn wound induction, the animals (n = 126) were treated with different CMC formulations, had their occlusive dressings changed daily and were followed through 7, 14 and 30 days. Morphometric, macroscopic and microscopic aspects and collagen quantification were evaluated. RESULTS: Significative wound contraction, granulation tissue formation, inflammatory infiltration and collagen fibers deposit throughout different phases of the healing process were observed in the CMC hydrogels treated groups. CONCLUSIONS: The results showed that, in the initial phase of the healing process, the most adequate product was the CMC/HA/Ag association, while in the other phases the CMC/HA association was the best one to promote the healing of burn wounds.

Does CO2 pneumoperitoneum in laparoscopy interfere with collagen deposition in abdominal surgical wounds?

Purpose To determine by histomorphometric analysis whether CO2 pneumoperitoneum interferes with collagen deposition in surgical wounds in the aponeurosis of rats. Methods This experiment involved 80 male Wistar rats, randomly allocated into four groups according to pneumoperitoneum period (PRE: 30 min preoperatively; POST: 30 min postoperatively; PP: 30 min pre- and postoperatively; C: control group). CO2 pneumoperitoneum was insufflated to 5 mmHg of pressure. A laparotomy was performed; 1 cm of the left colon was then resected, and an end-to-end anastomosis was performed to simulate surgical trauma, after which the abdominal wall was closed. On postoperative days 7 or 14, a sample of the abdominal wall was collected, stained with picrosirius red and observed under polarized light in an optical microscope. The amount of collagen was estimated by computerized histomorphometric analysis. Results There were no significant differences in collagen deposition between the control and experimental groups on postoperative days 7 (p=0.720) or 14 (p=0.933). The amount of collagen increased as expected in all groups between postoperative days 7 and 14 (p=0.0003). Conclusion At 5 mmHg, CO2 pneumoperitoneum does not interfere with collagen deposition in abdominal wall surgical wounds in rats.

Demyelination in experimental intraventricular neurocysticercosis.

Neurocysticercosis (NCC) is classified as a neglected tropical disease, which affects mainly Latin America and Africa in spite of some reports in North America and Europe. NCC represents the cause of up to 30% of the reported cases of epilepsy in endemic countries. The NCC injuries present direct relation to the development stage, location, and number of parasites as well as to the host immune response. This study aimed the characterization of the inflammatory response and tissue injuries by means of the analyses of the periventricular and parenchymatous demyelination through the experimental intraventricular NCC infection. Therefore, BALB/c mice were submitted to experimental NCC inoculation with Taenia crassiceps cysticerci. Their brains were removed at 7, 30, 60, and 90 days after the inoculation (DAI), and analyzed after staining with hematoxylin and eosin (HE), Luxol Fast Blue, and Nissl. It was possible to observe ventriculomegaly, inflammatory infiltration composed by polymorphonuclear and mononuclear cells, and foamy macrophages. The presence of inflammatory cells was associated with neurodegeneration detected by the areas with demyelination observed initially in the periventricular area and lately in the parenchyma. In conclusion, the presence of cysticerci and the consequent inflammation were able to promote initial periventricular demyelination followed by parenchymatous demyelination as the infection progressed.

Demyelination in experimental intraventricular neurocysticercosis / Desmielinização na neurocisticercose intraventricular experimental

Abstract Neurocysticercosis (NCC) is classified as a neglected tropical disease, which affects mainly Latin America and Africa in spite of some reports in North America and Europe. NCC represents the cause of up to 30% of the reported cases of epilepsy in endemic countries. The NCC injuries present direct relation to the development stage, location, and number of parasites as well as to the host immune response. This study aimed the characterization of the inflammatory response and tissue injuries by means of the analyses of the periventricular and parenchymatous demyelination through the experimental intraventricular NCC infection. Therefore, BALB/c mice were submitted to experimental NCC inoculation with Taenia crassiceps cysticerci. Their brains were removed at 7, 30, 60, and 90 days after the inoculation (DAI), and analyzed after staining with hematoxylin and eosin (HE), Luxol Fast Blue, and Nissl. It was possible to observe ventriculomegaly, inflammatory infiltration composed by polymorphonuclear and mononuclear cells, and foamy macrophages. The presence of inflammatory cells was associated with neurodegeneration detected by the areas with demyelination observed initially in the periventricular area and lately in the parenchyma. In conclusion, the presence of cysticerci and the consequent inflammation were able to promote initial periventricular demyelination followed by parenchymatous demyelination as the infection progressed.

Resumo A neurocisticercose (NCC) é classificada como uma doença tropical negligenciada que afeta principalmente a América Latina e a África, apesar de alguns relatos na América do Norte e na Europa. A NCC é responsável por cerca de 30% dos casos de epilepsia em países endêmicos. Estas lesões parecem ter estreita relação com o estádio de desenvolvimento, com a localização e o número de parasitas, bem como a resposta imune do hospedeiro. O presente estudo objetivou caracterizar a resposta de células inflamatórias e as lesões teciduais pela análise da desmielinização periventricular e parenquimatosa ao longo da infecção experimental de NCC intraventricular. Para tanto, camundongos BALB/c foram submetidos a NCC experimental através da inoculação de cisticercos de Taenia crassiceps. O encéfalo foi retirado aos 7, 30, 60 e 90 dias após inoculação (DAI) e analisado após coloração por Hematoxilina e Eosina (HE), Luxol Fast Blue e Nissl. Observou-se ventriculomegalia, processo de infiltração inflamatório composto por células polimorfonucleares, mononucleares e macrófagos espumosos. A presença de células inflamatórias foi associada com neurodegeneração, observada pelas áreas de desmielinização que foram inicialmente periventricular e mais tardiamente no parênquima. Em conclusão, observa-se que a presença dos cisticercos e a inflamação foram capazes de promover desmielinização periventricular inicial e parenquimatosa conforme houve progressão tardia da infecção.

Polymethyl Methacrylate (PMMA) in the Treatment of a Case of Hemifacial Microsomia.

Hemifacial microsomia (HMF) is a morphological alteration characterized by facial deformities. These alterations are a consequence of a congenital anomalous development of the first and second branchial arches. It may present a genetic or environmental origin or a mixture of both and is considered mostly multifactorial. The clinical presentation varies; however, some characteristics are predominant such as unilateral mandible hypoplasia, agenesis or malformation of the auricular pavilion, and agenesis or malformation of the eye globe. The aim of this paper was to report a clinical case of a patient with late diagnosis of HMF which presented multiple deformities and received treatment with polymethyl methacrylate (PMMA) implant in different concentrations. Aiming for facial harmony, the PMMA implant occurred in the following regions: canine fossa, nasolabial sulcus, mandible, Bichat Ball, chin outline, lip contour, nose base, columella, nose tip, and dorsum. The treatment resulted in significant improvement in the facial symmetry.

Partial inhibition of the main energetic pathways and its metabolic consequences after in vivo treatment with benzimidazole derivatives in experimental neurocysticercosis.

Benzimidazole derivatives such as albendazole (ABZ) and mebendazole are important molecules used in helminthic treatment. Neurocysticercosis is the main cause of acquired epilepsy throughout the world and is currently treated with ABZ. New molecules have been studied in order to aid in the treatment of this neglected tropical disease, among them RCB15 and RCB20. The aim of this study was to evaluate the metabolic impact of RCB15 and RCB20 on Taenia crassiceps cysticerci intracranially inoculated in Balb/c mice. Thirty days after the inoculation the mice were treated with 50 mg kg-1 of RCB15, RCB20, ABZ or NaCl 0.9%. The euthanasia and cysticerci removal were performed 24 h after the treatment. The cysticerci were analysed through high performance liquid chromatography. After the treatments, there was an impairment in the main energetic pathways such as glycolytic pathway, homolactic fermentation or in mitochondrion energy production detected through the decrease in pyruvate, lactate, oxaloacetate, malate and fumarate concentrations. This induced the parasite to resort to alternative energetic pathways such as proteins catabolism, propionate fermentation and fatty acids oxidation. Therefore, benzimidazole derivatives are a promising alternative to ABZ use as they also reach the brain tissue and induce a metabolic stress in the cysticerci.

Antiangiogenic potential of Jatropha curcas latex in the chick chorioallantoic membrane model / Potencial antiangiogênico do látex de Jatropha curcas em modelo de membrana corioalantoica de embrião de galinha

AIMS: To perform a physicochemical and phytochemical characterization of Jatropha curcas latex and to investigate its antiangiogenic potential. METHODS: We performed an initial physicochemical characterization of J. curcas latex using thermal gravimetric analyses and Fourier Transform Infrared spectroscopy. After that, phenols, tannins and flavonoids were quantified. Finally, the potential of J. curcas latex to inhibit angiogenesis was evaluated using the chick chorioallantoic membrane model. Five groups of 20 fertilized chicken eggs each had the chorioallantoic membrane exposed to the following solutions: (1) water, negative control; (2) dexamethasone, angiogenesis inhibitor; (3) Regederm®, positive control; (4) 25% J. curcas latex diluted in water; (5) 50% J. curcas latex diluted in water; and (6) J. curcas crude latex. Analysis of the newly-formed vascular net was made through captured images and quantification of the number of pixels. Histological analyses were performed to evaluate the inflammation, neovascularization, and hyperemia parameters. The results were statically analyzed with a significance level set at p<0.05. RESULTS: Physicochemical characterization showed that J. curcas latex presented a low amount of cis-1.4-polyisoprene, which reduced its elasticity and thermal stability. Phytochemical analyses of J. curcas latex identified a substantial amount of phenols, tannins, and flavonoids (51.9%, 11.8%, and 0.07% respectively). Using a chick chorioallantoic membrane assay, we demonstrated the antiangiogenic potential of J. curcas latex. The latex induced a decrease in the vascularization of the membranes when compared with neutral and positive controls (water and Regederm®). However, when compared with the negative control (dexamethasone), higher J. curcas latex concentrations showed no significant differences. CONCLUSIONS: J. curcas latex showed low thermal stability, and consisted of phenols, tannins, and flavonoids, but little or no rubber. Moreover, this latex demonstrated a significant antiangiogenic activity on a chick chorioallantoic membrane model. The combination of antimutagenic, cytotoxic, antioxidant and antiangiogenic properties makes J. curcas latex a potential target for the development of new drugs.

OBJETIVOS: Realizar uma caracterização físico-química e fitoquímica do látex de Jatropha curcas e investigar o seu potencial antiangiogênico. MÉTODOS: foi realizada uma caracterização físico-química inicial do látex de J. curcas utilizando as análises termogravimétricas e a espectroscopia com a Transformada de Fourier. Depois disso, fenóis, taninos e flavonoides foram quantificados. Finalmente, o potencial do látex de J. curcas em inibir a angiogênese foi avaliado através do uso de modelo de membrana corioalantoica de embrião de galinha. Cinco grupos, cada um com 20 ovos de galinha fertilizados, tiveram a membrana corioalantoica exposta às seguintes soluções: (1) água, controle negativo; (2) dexametasona, inibidor da angiogênese; (3) Regederm®, controle positivo; (4) 25% de látex de J. curcas diluído em água; (5) 50% de látex de J. curcas diluído em água; e (6) látex bruto de J. curcas. A análise da rede vascular recém-formada foi feita por meio de imagens capturadas e quantificação do número de pixels. Análises histológicas foram realizadas para avaliar os parâmetros de inflamação, neovascularização e hiperemia. Os resultados foram analisados estaticamente com nível de significância estabelecido em p<0,05. RESULTADOS: A caracterização físico-química mostrou que o látex de J. curcas apresenta uma baixa quantidade de cis-1,4-poliisopreno, o que reduz sua elasticidade e estabilidade térmica. Análises fitoquímicas do látex de J. curcas identificaram uma quantidade significativa de fenóis, taninos e flavonoides (51,9%, 11,8% e 0,07% respectivamente). Usando o modelo de membrana corioalantoica de ovo de galinha embrionado, demonstrou-se o potencial antiangiogênico do látex de J. curcas. O látex induziu a diminuição da vascularização das membranas, em comparação aos grupos controle neutro e positivo (água e Regederm®). CONCLUSÕES: O látex de J. curcas apresentou baixa estabilidade térmica, ausência ou pouca quantidade de borracha e presença de fenóis, taninos e flavonoides em sua composição. Além disso, apresentou alta atividade antiangiogênica no modelo de membrana corioalantoica de embrião de galinha. A combinação de propriedades antimutagênicas, citotóxicas, anti-inflamatórias, antioxidantes e antiangiogênicas faz com que o látex de J. curcas seja um alvo potencial para o desenvolvimento de novos medicamentos.

Histopathologic aspects of experimental cysticercosis and in situ cytokines profile in C57BL/6 mice.

Neurocysticercosis (NCC) is one of the parasitic infections that most affects the central nervous system. The knowledge regarding its immunopathogenesis and pathophysiology needs broadening. Taenia crassiceps cysticerci are used as the NCC experimental model. The aim of this work was to describe the general pathological processes and the in situ cytokine profile in C57BL/6 mice inoculated intracranially with viable T. crassiceps cysticerci. The histopathology analysis showed cysticerci in the extraparenchymal and intraventricular region, mononuclear inflammatory infiltration surrounding the parasite, microgliosis and meningitis. The analysis of the in situ immune profiles showed a predominance of the Th2 response. The IL-4 and IL-10 dosages were significantly increased in the infected group. The decrease in the INF-gamma dosage reflects the immunomodulation from the cysticerci. In conclusion, a T. crassiceps NCC infection in C57BL/6 mice triggers an inflammatory response, a predominance of Th2 type in situ profile, with mononuclear inflammatory cell infiltration, meningitis and microgliosis.

Histopathologic aspects of experimental cysticercosis and in situ cytokines profile in C57BL/6 mice / Aspectos histopatológicos da cisticercose experimental e perfil de citocinas in situ em camundongos C57BL/6

ABSTRACT Neurocysticercosis (NCC) is one of the parasitic infections that most affects the central nervous system. The knowledge regarding its immunopathogenesis and pathophysiology needs broadening. Taenia crassiceps cysticerci are used as the NCC experimental model. The aim of this work was to describe the general pathological processes and the in situ cytokine profile in C57BL/6 mice inoculated intracranially with viable T. crassiceps cysticerci. The histopathology analysis showed cysticerci in the extraparenchymal and intraventricular region, mononuclear inflammatory infiltration surrounding the parasite, microgliosis and meningitis. The analysis of the in situ immune profiles showed a predominance of the Th2 response. The IL-4 and IL-10 dosages were significantly increased in the infected group. The decrease in the INF-gamma dosage reflects the immunomodulation from the cysticerci. In conclusion, a T. crassiceps NCC infection in C57BL/6 mice triggers an inflammatory response, a predominance of Th2 type in situ profile, with mononuclear inflammatory cell infiltration, meningitis and microgliosis.

RESUMO Neurocisticercose (NCC) é uma das doenças parasitárias que mais afeta o sistema nervoso central. É necessário aprofundar o conhecimento em relação à sua imunopatogênese e patofisiologia. Os cisticercos de Taenia crassiceps são utilizados como modelo experimental para estudos da NCC. O objetivo deste trabalho foi descrever os processos patológicos gerais e o perfil de citocinas in situ em camundongos C57BL/6 inoculados via intracerebral com cisticercos viáveis de T. crassiceps. A análise histopatológica demonstrou cisticercos nas regiões extra-parenquimatosa e intraventricular, infiltrado inflamatório de células mononucleares ao redor do parasita, microgliose e meningite. A análise in situ do perfil de citocinas mostrou uma predominância da resposta Th2. As dosagens de IL-4 e IL-10 foram significativamente maiores no grupo infectado. Conclui-se que a NCC por T. crassiceps em camundongos C57BL/6 induz uma resposta inflamatória com predominância in situ de citocinas do perfil Th2, com infiltrado inflamatório de células mononucleares, meningite e microgliose.

Antitumor effectiveness and mechanism of action of Ru(II)/amino acid/diphosphine complexes in the peritoneal carcinomatosis progression.

Peritoneal carcinomatosis is considered as a potentially lethal clinical condition, and the therapeutic options are limited. The antitumor effectiveness of the [Ru(l-Met)(bipy)(dppb)]PF6(1) and the [Ru(l-Trp)(bipy)(dppb)]PF6(2) complexes were evaluated in the peritoneal carcinomatosis model, Ehrlich ascites carcinoma-bearing Swiss mice. This is the first study that evaluated the effect of Ru(II)/amino acid complexes for antitumor activity in vivo. Complexes 1 and 2 (2 and 6 mg kg-1) showed tumor growth inhibition ranging from moderate to high. The mean survival time of animal groups treated with complexes 1 and 2 was higher than in the negative and vehicle control groups. The induction of Ehrlich ascites carcinoma in mice led to alterations in hematological and biochemical parameters, and not the treatment with complexes 1 and 2. The treatment of Ehrlich ascites carcinoma-bearing mice with complexes 1 and 2 increased the number of Annexin V positive cells and cleaved caspase-3 levels and induced changes in the cell morphology and in the cell cycle phases by induction of sub-G1 and G0/G1 cell cycle arrest. In addition, these complexes reduce angiogenesis induced by Ehrlich ascites carcinoma cells in chick embryo chorioallantoic membrane model. The treatment with the LAT1 inhibitor decreased the sensitivity of the Ehrlich ascites carcinoma cells to complexes 1 and 2 in vitro-which suggests that the LAT1 could be related to the mechanism of action of amino acid/ruthenium(II) complexes, consequently decreasing the glucose uptake. Therefore, these complexes could be used to reduce tumor growth and increase mean survival time with less toxicity than cisplatin. Besides, these complexes induce apoptosis by combination of different mechanism of action.

Mode of action of the main anti-parasitic drugs

Neglected tropical diseases affect more than 1 billion people in tropical and subtropical regions most of them are caused by parasites. Several of these diseases already have effective drugs capable of eliminating the causative parasite, however are not capable of interrupting the transmission cycle. This fact induces the continuous of repetitive treatments, which may result in the parasite's resistance. This review aims to show the mechanism of action of the main drugs used to treat parasitic neglected tropical diseases in order to determine the drug's target and help the understanding of how the parasites are killed within the host.

Experimental neurocysticercosis: absence of IL-4 induces lower encephalitis / Neurocisticercose experimental: ausência de IL-4 induz menos encefalite

ABSTRACT Neurocysticercosis (NCC) is the most severe clinical manifestation of cysticercosis. One of the factors responsible for its symptomatology is the host inflammatory response. Therefore the influence of interleukin 4 (IL-4) on the induction of encephalitis in experimental NCC was evaluated. Methods BALB/c (WT) and BALB/c (IL-4-KO) mice were inoculated intracranially with Taenia crassiceps cysticerci and euthanized at 7, 30, 60 and 90 days later, the encephala removed and histopathologically analyzed. Results The absence of IL-4 induced greater parasitism. In the initial phase of the infection, IL-4-KO showed a lower intensity in the inflammatory infiltration of polimorphonuclear cells in the host-parasite interface and intra-parenquimatous edema. The IL-4-KO animals, in the late phase of the infection, showed lower intensity of ventriculomegaly, encephalitis, and meningitis, and greater survival of the parasites in comparison with the WT animals. Conclusion The absence of IL-4 induced lower inflammatory infiltration, ventriculomegaly and perivasculitis in experimental NCC.

RESUMO A Neurocisticercose (NCC) é a manifestação clínica mais severa da cisticercose, e um dos fatores responsáveis pela sintomatologia é a resposta inflamatória do hospedeiro. Desta forma avaliou-se a influência da interleucina 4 (IL-4) na indução de encefalite na NCC experimental. Métodos Camundongos das linhagens BALB/c (WT) e BALB/c (IL-4-KO) foram inoculados intracranialmente com cisticercos de Taenia crassiceps e eutanasiados aos 7, 30, 60 e 90 dias após a infecção, os encéfalos foram removidos e analisados histopatologicamente. Resultados A ausência da IL-4 induziu um maior parasitismo nos animais. Na fase inicial da infecção os animais IL-4-KO apresentaram menor intensidade tanto de infiltrado inflamatório de polimorfonucleares na interface parasito-hospedeiro quanto de edema intraparenquimatoso. Os animais IL-4-KO, na fase tardia, apresentaram menor intensidade de ventriculomegalia, encefalite, meningite e maior sobrevivência dos cisticercos em relação aos animais WT. Conclusão A ausência da IL-4 induz menos infiltrado inflamatório, ventriculomegalia e perivasculite na NCC experimental.