Benzydamine induces apoptosis in astrocytes in vitro / Benzadamina induz apoptose em astrócitos in vitro

Objective: the present work aims to evaluate the Benzydamine (BZD) effect on cell viability in astrocyte culture and investigated the death mechanism involved with its cytotoxic effect. Methods: in order to evaluate cell viability, the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay was used, while flow cytometry was used to verify cell damage. The immunofluorescence assay was used to verify the expression of the marker's caspase-8, caspase9 and p65 subunit of Factor nuclear kappa B (NFκB). A statistical analysis for MTT assay and Flow Cytometry were made using ANOVA with Dunett's post-test; Student's t-test was made for the Immunofluorescence. Significance was set at p < 0.05. Results: the MTT reduction assay showed that BZD (3.1 to 100 µg/mL) caused a decrease in astrocytes viability. The flow cytometry showed that the cytotoxic effect of BZD was caused by the activation of the apoptotic death pathway, evidenced by the externalization of phosphatidylserine. The immunofluorescence revealed an increase in caspase-8 expression and no alteration in caspase-9 expression, demonstrating that there was an activation of the extrinsic pathway of apoptosis. The mean inhibitory concentration (IC50) of BZD (26.13 µg/mL) also caused an increase in NFκB p65 expression. Conclusion: taken together, the results of the present study suggest that BZD has a cytotoxic effect on astrocyte cells, and this effect comes from its ability to activate the extrinsic apoptotic pathway

Objetivo: o presente trabalho tem como objetivo avaliar o efeito da Benzidamina (BZD) na viabilidade celular em cultura de astrócitos e investigar o mecanismo de morte envolvido com seu efeito citotóxico. Métodos: para avaliar a viabilidade celular foi utilizado o ensaio de redução do brometo de 3-(4,5-Dimetiltiazol-2-il)-2,5-difeniltetrazólio (MTT), enquanto a citometria de fluxo foi utilizada para verificar o dano celular. O ensaio de imunofluorescência foi utilizado para verificar a expressão do marcador caspase-8, caspase9 e subunidade p65 do Fator nuclear kappa B (NFκB). A análise estatística para ensaio MTT e Citometria de Fluxo foi feita utilizando ANOVA com pós-teste de Dunett; Foi feito o teste t de Student para Imunofluorescência. A significância foi estabelecida em p < 0,05. Resultados: o ensaio de redução do MTT mostrou que o BZD (3,1 a 100 µg/mL) causou diminuição na viabilidade dos astrócitos. A citometria de fluxo mostrou que o efeito citotóxico do BZD foi causado pela ativação da via de morte apoptótica, evidenciada pela externalização da fosfatidilserina. A imunofluorescência revelou aumento na expressão de caspase-8 e nenhuma alteração na expressão de caspase-9, demonstrando que houve ativação da via extrínseca de apoptose. A concentração inibitória média (CI50) de BZD (26,13 µg/mL) também causou aumento na expressão de NFκB p65. Conclusão: em conjunto, os resultados do presente estudo sugerem que o BZD tem efeito citotóxico nas células astrocitárias, e esse efeito advém de sua capacidade de ativar a via apoptótica extrínseca.

Molecular epidemiology and antimicrobial resistance in Clostridioides difficile strains isolated from children and adolescents in a tertiary referral pediatric hospital in Fortaleza, Brazil

Abstract Background C. difficile has been increasingly reported as a cause of gastrointestinal disease in children, ranging from mild self-limiting diarrhea to severe conditions such as pseudomembranous colitis and toxic megacolon. Only two pediatric research groups reported the presence of C. difficile infection in Brazilian children, but no previous research has examined C. difficile infection among children in northeastern Brazil. This prospective cross-sectional study investigated the molecular epidemiology and antimicrobial resistance of C. difficile strains isolated from children and adolescents with diarrhea referred to a tertiary pediatric hospital in Brazil while exploring the associated risk factors. Results Toxin positivity or C. difficile isolation was found in 30.4 % (17/56) samples. C. difficile was isolated from 35 % (6/17) samples. Four toxigenic strains were identified (tpi+, tcdA+, tcdB+, cdtB-, without tcdC deletions) belonging to PCR ribotypes and PFGE-pulsotypes: 046 (new pulsotype 1174), 106 (NAP11), 002 (new pulsotype 1274), 012 (new pulsotype NML-1235). Two of the six isolates belonging to ribotypes 143 and 133 were non-toxigenic. All toxigenic strains were sensitive to metronidazole and vancomycin. Regarding the clinical manifestation, diarrhea lasted an average of 11 days, ranging from 3 to 50 days and was often associated with mucus and/or blood. All six patients from whom the C. difficile was isolated had a chronic disease diagnosis, with these comorbidities as the main risk factors. Conclusion Our study enhances our understanding of the present epidemiological landscape of C. difficile-associated diarrhea (CDI) among children in northeastern Brazil, reveling a substantial CDI frequency of 30.4 %, with toxigenic strains detected in 76.4 % of cases, highlighting a higher prevalence compared to earlier Brazilian studies. In the globalized world, an understanding of disease-generating strains, the associated risk factors, clinical manifestation, and antimicrobial sensitivity has fundamental epidemiological importance and draws attention to preventive measures, allowing for more decisive action.

Gliclazide reduced oxidative stress, inflammation, and bone loss in an experimental periodontal disease model

Abstract Objective The aim of this study was to evaluate the effects of gliclazide on oxidative stress, inflammation, and bone loss in an experimental periodontal disease model. Material and Methods Male albino Wistar rats were divided into no ligature, ligature, and ligature with 1, 5, and 10 mg/kg gliclazide groups. Maxillae were fixed and scanned using micro-computed tomography to quantify linear and bone volume/tissue volume (BV/TV) and volumetric bone loss. Histopathological, immunohistochemical and immunofluorescence analyses were conducted to examine matrix metalloproteinase-2 (MMP-2), cyclooxygenase 2 (COX-2), cathepsin K, members of the receptor activator of the nuclear factor kappa-Β ligand (RANKL), receptor activator of nuclear factor kappa-Β (RANK), osteoprotegerin (OPG) pathway, macrophage migration inhibitory factor (MIF), superoxide dismutase-1 (SOD-1), glutathione peroxidase-1 (GPx-1), NFKB p 50 (Cytoplasm), NFKB p50 NLS (nuclear localization signal), PI3 kinase and AKT staining. Myeloperoxidase activity, malondialdehyde and glutathione levels, while interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels were evaluated by spectroscopic ultraviolet-visible analysis. A quantitative reverse transcription polymerase chain reaction was used to quantify the gene expression of the nuclear factor kappa B p50 subunit (NF-κB p50), phosphoinositide 3-kinase (PI3k), protein kinase B (AKT), and F4/80. Results Micro-computed tomography showed that the 1 mg/kg gliclazide treatment reduced linear bone loss compared to the ligature, 5 mg/kg gliclazide, and 10 mg/kg gliclazide treatments. All concentrations of gliclazide increased bone volume/tissue volume (BV/TV) compared to the ligature group. Treatment with 1 mg/kg gliclazide reduced myeloperoxidase activity, malondialdehyde, IL-1β, and TNF-α levels (p≤0.05), and resulted in weak staining for COX-2, cathepsin k, MMP-2, RANK, RANKL, SOD-1, GPx-1,MIF and PI3k. In addition, down-regulation of NF-κB p50, PI3k, AKT, and F4/80 were observed, and OPG staining was strong after the 1 mg/kg gliclazide treatment. Conclusions This treatment decreased neutrophil and macrophage migration, decreased the inflammatory response, and decreased bone loss in rats with ligature-induced periodontitis.

Study of the protective effect of dexamethasone on cisplatin-induced ototoxicity in rats

Abstract Purpose: To evaluate the ability of dexamethasone to protect against cisplatin (CDDP)-induced ototoxicity. Methods: Male Wistar rats were divided into the following three groups: 1) Control (C): 6 animals received intraperitoneal (IP) saline solution, 8 ml/kg/day for four days; 2) C + CDDP: 11 animals received 8 ml/kg/day of IP saline and, 90 min after saline administration, 8 mg/kg/day of IP CDDP for four days; and 3) DEXA15 + CDDP: 11 animals received IP dexamethasone 15 mg/kg/day and, 90 min after dexamethasone administration, received 8 mg/kg/day of IP CDDP for four days. Results: It was found that dexamethasone did not protect against weight loss in CDDP-exposed animals. The mortality rate was comparable with that previously reported in the literature. The auditory threshold of animals in the DEXA15 + CDDP group was not significantly altered after exposure to CDDP. The stria vascularis of animals in the DEXA15 + CDDP group was partially preserved after CDDP exposure. Conclusions: Dexamethasone at the dose of 15 mg/kg/day partially protected against CDDP-induced ototoxicity, based on functional evaluation by brainstem evoked response audiontry (BERA) and morphological evaluation by optical microscopy. However, dexamethasone did not protect against systemic toxicity.

Role of the route of leukotrienes in an experimental model of oral mucositis induced by 5-fluorouracil

Abstract Purpose: To investigate the participation of cysteinyl leukotrienes in the pathophysiology of oral mucositis. Methods: Oral mucositis was induced in hamsters using 5-fluorouracil (5-FU; 60 and 40 mg/kg; i.p., on days 1 and 2, respectively, and with excoriations in jugal mucosa on day 4). Montelukast (10, 20, or 40 mg/kg/d; gavage), MK886 (3 mg/kg/d, i.p.), or saline or celecoxib (7.5 mg/kg/d; i.p.) was administered 1 h prior to 5-FU and daily, until the fourth (MK886) or tenth day, when the animals were euthanized and their jugal mucosa was collected for macroscopic, histopathological, and immunohistochemical evaluation. Results: Neither montelukast nor MK-886 prevented the oral mucositis induced by 5-FU, as observed by histopathological evaluation. In addition, we did not find significant differences in the expression of inducible nitric oxide synthase-2, cyclooxygenase-2, or interleukin (IL)-1β between the experimental and control groups. However, we did observe a significant decrease in tumor necrosis factor (TNF)-α expression for all doses of montelukast; we also observed a significant decrease in IL-10 with 40 mg/kg/d and MK 886. Conclusions: Cysteinyl leukotrienes do not play an important role in experimental oral mucositis induced by 5-FU. There is a modulating action specifically on TNF-α.

Oil mixes omega 9, 6 and 3, enriched with seaweed, promoted reduction of thermal burned modulating NF-kB and Ki-67

PURPOSE: To examine the effects of the oil mixes (ω-9, ω-6 and ω-3) in rats subjected to thermal burn. It was also aimed to assess whether the sources of ω3 would interfere with the effect of such mixes on the thermal injury. METHODS: Thirty-six rats distributed into five groups: burned + water, burned + isolipid mix, burned + oil mix 1 (ALA), burned + oil mix 2 (ALA + EPA + DHA of fish) and burned + oil mix 3 (ALA + DHA from seaweed). The thermal injury was involving total thickness of skin. After the burns animals received the oil mixes for seven days. The lesions were evaluated by immunohistochemistry. RESULTS: Animals receiving mix 3 showed a smaller extension of the thermal injury as compared to those that were supplemented with other oils mixes. Expression of Ki-67 in the receiving Mix 3 increased as compared to all the other groups. Animals supplemented with mix 3 were able to inhibit NF-κB in injured tissue. CONCLUSION: Rats received oil mix in which the source of ω3 (ALA+DHA of seaweed) showed inhibition of NF-κB, increase in cell proliferation, and reduction the extension of thermal lesion. .

Electroacupuncture ameliorates experimental colitis induced by TNBS through activation of interleukin-10 and inhibition of iNOS in mice

PURPOSE:To study the anti-inflammatory actions of electroacupuncture (EAc) on an experimental colitis model in mice.METHODS:Thirty-eight male Swiss mice, divided in five groups, were subjected to induction of colitis by TNBS in 50% ethanol. Saline (SAL) and ethanol (ETNL) groups served as controls. TNBS+EAc and TNBS+ dexamethasone subgroups were treated with EAc 100Hz and dexamethasone (DEXA) 1 mg/Kg/day, respectively. After three days, a colon segment was obtained for quantification of myeloperoxidase (MPO) activity, immunohistochemistry for iNOS, malondialdehyde (MDA) and cytokines (IL-1β and IL-10).RESULTS:Neutrophilic activity, assayed as MPO activity, was significantly higher in the TNBS colitis group than that in the saline control group. TNBS+EAc group showed suppression of IL-10 in the colon. EAc treatment significantly reduced the concentration of MDA and the expression of iNOS, as compared to the other groups. CONCLUSION: Electroacupuncture 100Hz applied to acupoint ST-36 promotes an anti-inflammatory action on the TNBS-induced colitis, mediated by increase of IL-10 and decrease of iNOS expression.

Electroacupuncture ameliorates experimental colitis induced by TNBS through activation of interleukin-10 and inhibition of iNOS in mice

PURPOSE: To study the anti-inflammatory actions of electroacupuncture (EAc) on an experimental colitis model in mice. METHODS: Thirty-eight male Swiss mice, divided in five groups, were subjected to induction of colitis by TNBS in 50% ethanol. Saline (SAL) and ethanol (ETNL) groups served as controls. TNBS+EAc and TNBS+ dexamethasone subgroups were treated with EAc 100Hz and dexamethasone (DEXA) 1 mg/Kg/day, respectively. After three days, a colon segment was obtained for quantification of myeloperoxidase (MPO) activity, immunohistochemistry for iNOS, malondialdehyde (MDA) and cytokines (IL-1β and IL-10). RESULTS: Neutrophilic activity, assayed as MPO activity, was significantly higher in the TNBS colitis group than that in the saline control group. TNBS+EAc group showed suppression of IL-10 in the colon. EAc treatment significantly reduced the concentration of MDA and the expression of iNOS, as compared to the other groups. CONCLUSION: Electroacupuncture 100Hz applied to acupoint ST-36 promotes an anti-inflammatory action on the TNBS-induced colitis, mediated by increase of IL-10 and decrease of iNOS expression. .

Immunohistochemccal approach reveals localizatin of cystathionine--lyase and ccystathionine--synthetase in ethanol-induced gastric mucosa damage in mice

Context Hydrogen sulphide (H2S) has been proved to be a neuromodulator and contributes to the maintenance of gastric mucosal integrity in damage caused by anti-inflammatory nonsteroidal drugs. Previously, we demonstrated that H2S synthesis is essential to gastric protection against ethanol. Objective To better understanding the role of H2S and the detailed localization of its production in both normal and injured stomach due to ethanol injection, we studied the expression of cystathionine-γ-lyase (CSE) and cystathionine-β-synthetase (CBS) isoforms in gastric mucosa of mice treated with saline or 50% ethanol. Methods Mice were treated by gavage with saline or 50% ethanol (0.5 mL/25 g). After 1 hour, mice were sacrificed, and gastric tissue was evaluated by histological and immunohistochemical analysis specific for CSE and CBS. Results We have demonstrated a non-specific expression of CBS in the normal gastric mucosa and expression of CSE occurring mainly in the parietal cells of the animals treated with ethanol. Conclusion Thus, we demonstrated that the expression of CBS appears to be constitutive and diffuse across the gastric epithelium, while the expression of CSE appears to be induced in parietal cells by damage agents such as ethanol. .

Contexto O sulfeto de hidrogênio (H2S) tem sido mostrado como um neuromodulador e contribuidor para a manutenção da integridade da mucosa gástrica na lesão causada por drogas antiinflamatórias não esteroidais. Previamente, demonstramos que a síntese de H2S é essencial para a proteção da mucosa gástrica contra a administração de etanol. Objetivo Para compreender o papel do H2S e a localização detalhada de sua produção no estômago normal e após lesão induzida pela administração de etanol, estudou-se a expressão das isoformas cistationina-γ-liase (CSE) e cistationina-β-sintetase (CBS) na mucosa gástrica de camundongos tratados com salina ou etanol 50%. Métodos Os camundongos foram tratados por gavagem com salina ou etanol 50% (0,5 mL/25 g). Após 1 hora, os camundongos foram sacrificados e os tecidos gástricos foram avaliados por análise histológica e imunoistoquímica específica para CBS e CSE. Resultados Foi demonstrado expressão não específica de CBS na mucosa gástrica normal e expressão de CSE ocorrendo principalmente nas células parietais dos animais tratados com etanol. Conclusão Assim, demonstramos que a expressão de CBS parece ser constitutiva e difusa através do epitélio gástrico, enquanto a expressão de CSE parece ser induzida nas células parietais por agentes lesivos como o etanol. .

Changes in morphology of long bone marrow tissue of rats submitted to cryotherapy with liquid nitrogen / Alterações na morfologia do tecido medular de ossos longos de ratos submetido à crioterapia com nitrogênio líquido

PURPOSE: To study the main effects of local use of liquid nitrogen on bone marrow tissue in rats. METHODS: The femoral diaphyses of 42 Wistar rats were exposed to three local and sequential applications of liquid nitrogen for one or two minutes, intercalated with periods of five minutes of passive thawing. The animals were sacrificed after one, two, four and 12 weeks and the specimens obtained were analyzed histomorphologically. RESULTS: In the second experimental week of one-minute protocol, histological degree of inflammation obtained a mean score of one (mild), ranging from 0 (absent or scarce) and two (moderate) (Kruskal-Wallis test p=0.01). In the second experimental week of two-minute protocol, degree of inflammation to the medullar tissue obtained an average score of two (Kruskal-Wallis test p=0.01). CONCLUSION: The degree of inflammation of the bone marrow tissue was higher in protocol of three applications of two minutes compared to protocol of three applications of one minute.

OBJETIVO: Investigar os principais efeitos do uso local de nitrogênio líquido sobre o tecido medular ósseo em ratos. MÉTODOS: As diáfises femorais de 42 ratos Wistar foram expostas a três aplicações sequenciais locais de nitrogênio líquido por um ou dois minutos, intercaladas por períodos de cinco minutos de degelo espontâneo. Os animais foram sacrificados após uma, duas, quatro e 12 semanas e os espécimes obtidos foram analisados histomorfologicamente. RESULTADOS: Na segunda semana experimental do protocolo de um minuto, o grau histológico de inflamação obteve um escore médio de um (leve) variando entre 0 (ausente ou escarço) a dois (moderado) (Teste de Kruskal-Wallis p=0.01). Na segunda semana experimental do protocolo de dois minutos, o grau histológico de inflamação do tecido medular obteve um escore máximo de dois (moderado) (Teste de Kruskal-Wallis p=0.01). CONCLUSÃO: O grau de inflamação do tecido medular ósseo foi maior no protocolo de três aplicações de dois minutos comparado ao protocolo de três aplicações de um minuto.

Histomorphometric assessment of bone necrosis produced by two cryosurgery protocols using liquid nitrogen: an experimental study on rat femurs

OBJECTIVE: The aim of this study was to evaluate the effects of liquid nitrogen cryosurgery on the femoral diaphysis of rats. MATERIAL AND METHODS: The femoral diaphyses of 42 Wistar rats were exposed to three local and sequential applications of liquid nitrogen for 1 or 2 min, intercalated with periods of 5 min of passive thawing. The animals were sacrificed after 1, 2, 4 and 12 weeks and the specimens obtained were processed and analyzed histomorphometrically. RESULTS: The depth and extent of peak bone necrosis were 124.509 µm and 2087.094 µm for the 1-min protocol, respectively, and 436.424 µm and 12046.426 µm for the 2-min protocol. Peak necrosis was observed in the second experimental week with both cryotherapy protocols. CONCLUSIONS: The present results indicate that the 2-min protocol produced more marked bone necrosis than the 1-min protocol. Although our results cannot be entirely extrapolated to clinical practice, they contribute to the understanding of the behavior of bone tissue submitted to different cycles of liquid nitrogen freezing and may serve as a basis for new studies.

The role of apoptosis in cisplatin-induced ototoxicity in rats / Papel da apoptose na ototoxicidade por cisplatina em ratos

Cisplatin is a chemotherapy agent frequently used to treat different types of neoplasia. Ototoxicity is one of the side-effects which cause significant morbidity and limits its use. This study aimed at assessing the role of apoptosis in cisplatin-induced ototoxicity. DESIGN: experimental study. MATERIALS AND METHODS: male Wistar rats were treated with intraperitoneal cisplatin, in the doses of 24 and 16 mg/kg. The animals were assessed by means of distortion product evoked otoacoustic emissions (DPEOAE) or brainstem evoked auditory potentials (BEAP) in the third (D3) and fourth (D4) days after drug infusion onset. Following that, their cochleas were removed for immunohistochemical studies of apoptosis - TUNEL method. RESULTS: the group treated with 24 mg/kg showed a significant reduction in DPEOAE amplitude, and such fact was not seen with the 16 mg/kg. Both doses caused an increase in BEAP electrophysiological threshold in D3 and D4. Apoptosis was the injury mechanism responsible for the cisplatin-induced ototoxicity - 16 mg/kg dose, when the animals were assessed on D3. CONCLUSION: apoptosis may be involved in the cisplatin-induced ototoxicity, depending on the dose and time of injury assessment.

Cisplatina é um agente quimioterápico frequentemente usado para o tratamento de várias linhagens de neoplasias. A ototoxicidade é um dos efeitos colaterais causadores de significativa morbidade e que limita sua utilização. Este estudo teve por objetivo avaliar o papel da apoptose na ototoxicidade por cisplatina. DESENHO DO ESTUDO: Estudo experimental. MATERIAL E MÉTODO: Ratos Wistar machos foram tratados com cisplatina, via intraperitoneal, nas doses de 24 e 16 mg/kg. Os animais foram avaliados através de emissões otoacústicas evocadas produtos de distorção (EOAPD) ou potenciais auditivos evocados de tronco encefálico (PAETE) no terceiro (D3) e quarto (D4) dias após o início da infusão das drogas. Em seguida suas cócleas foram removidas para estudo de imunoistoquímica para apoptose, método TUNEL. RESULTADOS: O grupo tratado com 24 mg/kg mostrou diminuição significativa da amplitude das EOAPD, fato não observado com a dose de 16 mg/kg. Ambas as doses promoveram aumento do limiar eletrofisiológico pelo PAETE no D3 e D4. A apoptose foi o mecanismo de lesão responsável pela ototoxicidade da cisplatina, dose de 16 mg/kg, quando os animais foram avaliados no D3. CONCLUSÃO: Apoptose pode estar envolvida no mecanismo de ototoxicidade pela cisplatina, na dependência da dose e tempo de avaliação da lesão.

Distortion-product otoacoustic emissions and auditory brainstem responses sensitivity assessment in cisplatin-induced ototoxicity in rats / Avaliação da sensibilidade das emissões otoacústicas produtos de distorção e dos potenciais auditivos evocados de tronco encefálico na ototoxicidade por cisplatina em ratos

Cisplatin (cis-diamminedicloroplatinum) is an antineoplastic drug used in the treatment of a variety of cancers, especially head-and-neck cancer. Its ototoxicity, however, has been noted as a common side-effect which limits its use and causes significant morbidity. AIM: to assess distortion-product otoacoustic emissions (DPOAE) and brainstem evoked response audiometry (BERA) sensitivity to detect secondary ototoxicity caused by different doses and means of administration of cisplatin in rats. STUDY DESIGN: Experimental. MATERIAL AND METHODS: Male Wistar rats were intraperitoneally (i.p.) injected with 24 mg/kg cisplatin, divided into three equal doses (8mg/kg) or a single i.p. injection of 16 mg/kg. The animals were evaluated by distortion product otoacoustic emission (DPOAE) or brainstem evoked response audiometry (BERA) on the 3rd and 4th days after the cisplatin injection. RESULTS: Treatment with cisplatin 24 mg/kg resulted in significant DPOAE decrease and it raised the BERA electrophysiological threshold. The 16mg/kg dose could not significantly reduce the DPOAE amplitude, but it raised the animals' hearing thresholds - detected by the BERA. CONCLUSION: In rats, BERA was more sensitivity than DPOAE at detecting cisplatin-induced ototoxicity in rats considering different doses and means of administration.

Cisplatina (cisdiaminodicloroplatinum) é um agente quimioterápico usado para o tratamento de várias linhagens de neoplasias, mormente as de cabeça e pescoço. Sua ototoxicidade permanece sendo um dos efeitos colaterais causadores de significativa morbidade e limita sua utilização. OBJETIVO: Avaliar a sensibilidade das emissões otoacústicas evocadas produtos de distorção (EOAPD) e potenciais auditivos evocados de tronco encefálico (PAETE) na detecção da ototoxicidade secundária a diferentes doses e formas de administração de cisplatina em ratos. FORMA DE ESTUDO: Experimental. MATERIAL E MÉTODO: Ratos Wistar machos, administrou-se cisplatina por via intraperitoneal (IP) nas doses de 24 mg/kg, fracionada em três doses diárias ou 16 mg/kg em infusão única. Avaliaram-se os animais através de EOAPD ou PAETE no terceiro (D3) e quarto (D4) dias após o início da infusão das drogas. RESULTADOS: O grupo tratado com 24 mg/kg mostrou diminuição significativa da amplitude das EOAPD e aumento do limiar eletrofisiológico pelo PAETE. A dose de 16 mg/kg não foi capaz de promover redução significativa da amplitude das EOAPD, mas elevou o limiar auditivo dos animais, detectado através de PAETE. CONCLUSÃO: Em ratos, os PAETE foram mais sensíveis que as OEAPD na detecção da ototoxicidade por cisplatina para diferentes doses e formas de administração.

Effect of a combination of medium chain triglycerides, linoleic acid, soy lecithin and vitamins A and E on wound healing in rats / Efeito da combinação de triglicerídeos de cadeia média, ácido linoléico, lecitina de soja e vitaminas A e E na cicatrização de ferida em ratos

PURPOSE: The aim of the study was to determine the effect of a combination of medium chain triglycerides (caprylic, capric, caproic and lauric acids), linoleic acid (essential fatty acid), vitamins A and E and soy lecithin, through a morphometric study, on the wound healing kinetics of experimental cutaneous ulcers. METHODS: A total of 45 male Wistar rats were used, in which a skin flap of total thickness with an area of 4 cm² was removed. The animals were divided randomly into 3 groups of 15 rats each, Control, Reference and Test groups, which were treated topically with 0.9 percent NaCl, a preparation of clostebol combined with neomycin sulfate and the test formulation, respectively. The wound areas were measured by digital planimetry at days zero, 3, 7 and 12 postoperative. Based on the wound area, we determined the degree of tissue repair and mean rate of repair at different time intervals. RESULTS: At day 3, an expansion of the wound area was observed in the Reference group and slight contraction in the Control and Test groups. On the subsequent days, the healing process, according to the degree of repair, proceeded in a linear manner, such that, at day 12, the healed area reached 77.95 percent of the initial ulcerated region in the Control group, 78.40 percent in the Reference group and 83.49 percent in the Test group, showing no significant differences. The overall mean rate of repair was equally similar at 12 days of treatment: 25.79 mm²/dia in the Control group, 25.42 mm²/dia in the Reference group and 27.38 mm²/dia in the Test group. CONCLUSION: The test preparation, applied topically on the experimentally induced cutaneous ulcers in rats, did not accelerate the process of tissue repair by secondary union.

OBJETIVO: Avaliar o efeito da associação de triglicerídeos de cadeia média (ácidos caprílico, cáprico, capróico e láurico), ácido linoléico (ácido graxo essencial), vitaminas A e E e lecitina de soja, através de estudo morfométrico, na cinética de reparação de úlceras cutâneas experimentais. MÉTODOS: Utilizaram-se 45 ratos, machos, da linhagem Wistar, nos quais foi removido um retalho cutâneo de espessura total com 4 cm² de área. Os animais foram divididos aleatoriamente em 3 grupos constituídos de 15 ratos, Controle, Referência e Teste, que foram tratados por via tópica respectivamente, com solução salina 0,9 por cento, composto de clostebol associado a sulfato de neomicina e a formulação em teste. As áreas das feridas foram mensuradas por planimetria digital nos dias zero, 3, 7 e 12 de pós-operatório. A partir da área da ferida, calcularam-se ainda o grau de reparação e a taxa média de reparação em intervalo de tempo. RESULTADOS: No 3o dia observou-se uma expansão da área da ferida no grupo referência e uma leve contração nos grupos controle e teste. Nos dias subseqüentes o processo de reparação, medido pela variável grau de reparação, evoluiu de forma linear, de modo que, no 12º dia, a área reparada alcançou 77,95 por cento da região ulcerada inicial no grupo Controle, 78,40 por cento no grupo Referência e 83,49 por cento no grupo Teste, não sendo constatadas diferenças estatisticamente significante. Igualmente semelhantes foram os valores da taxa média de reparação referente aos 12 dias de tratamento: 25,79 mm²/dia no grupo Controle, 25,42 mm²/dia no grupo Referência e 27,38 mm²/dia no grupo Teste CONCLUSÃO: O composto em Teste, aplicado por via tópica em úlceras cutâneas experimentalmente induzidas em ratos, não acelerou o processo de reparação recidual por segunda intenção.

Principais mediadores inflamatórios envolvidos na fisiopatologia da periodontite: papel de moduladores farmacológicos / Main inflammatory mediators involved in the physiopathology of periodontitis: role of pharmacological modulators

A periodontite é uma doença inflamatória caracterizada por infiltrado leucocitário, perda de tecidos de sustentação, reabsorção do osso alveolar e formação de bolsas periodontais. A gravidade da doença está associada com os mecanismos de resposta do hospedeiro a fatores microbianos uma vez que componentes dessas bactérias são capazes de ativar as células de defesa do hospedeiro determinando a liberação de mediadores que estimulam o dano tecidual. Esses mediadores incluem uma variedade de moléculas tais como citocinas, especialmente IL-1β e TNF-α; prostaglandinas, como PGE2; enzimas hidrolíticas, como as metaloproteinase de matriz (MMP) e o óxido nítrico (NO), um mediador importante que determina eventos de sinalização extra e intracelular, produzindo dentre outros efeitos biológicos, relaxamento da musculatura lisa, com a conseqüente vasodilatação e broncodilatação. Além disso, o NO atua em eventos inflamatórios afetando o metabolismo ósseo. Em conjunto, esses mediadores são responsáveis pela extensão e gravidade da doença. O objetivo dessa revisão foi discutir os principais mediadores inflamatórios envolvidos na patogênese da doença periodontal e o papel de moduladores farmacológicos nesse processo, na perspectiva de contribuir para a compreensão dos fenômenos associados com a lise óssea e a busca de tratamentos que possam alterar o curso evolutivo da doença periodontal.

Periodontitis is an inflammatory disease characterized by leukocyte infiltration, connective tissue loss, alveolar boneresorption and periodontal pocket formation. The disease severity is associated with host resistance to microbial factors since bacteria have the capacity to activate host defense cells, which in turn produce and release mediators that stimulate connective tissue breakdown. These mediators are a wide array of molecules including cytokines, especially IL-1β and TNF-α; prostaglandins, such as PGE2; hydrolytic enzymes, such matrix metalloproteinases (MMP) and nitric oxide (NO), a key mediator which elicits both extra and intracellular signaling events, producing among other effects relaxation of smooth musculature, causing vase and broncodilation asbiological action. Furthermore, NO is considered to act during inflammatory process affecting bone metabolism. Together, those mediators determine the extent and duration of degradative activity. The objective of this review was to discuss the main inflammatory mediators involved in periodontitis pathogenesis and the role of pharmacological modulators in severity disease making an effort to understand the mechanism involved in bone destruction highlighting treatments that may change the periodontal disease severity.

Effect of soluble fiber or fructooligosaccharide supplementation upon trinitrobenzenesulphonic acid induced colitis in rats / Efeito da suplementação de fibra solúvel ou frutooligossacarídeo na colite induzida por ácido trinitrobenzenossulfônico em ratos

PURPOSE: To evaluate the effect of soluble fiber or fructooligosaccharide (FOS) supplementation upon trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. METHODS: 64 Wistar rats were given water, soluble fiber or FOS intragastrically during 14 days prior to colitis induction with TNBS (n=48) or rectal enema with water (n=16; control group). On the 7th or 14th day following colitis induction the rats were weighed and euthanized in order to determine the colon weight/length ratio and macroscopic and microscopic scores. RESULTS: On the 7th day following colitis induction the body weight had decreased significantly, the colon weight/length ratio had increased and macroscopic and microscopic colon lesions were observed. On the 14th day following colitis induction no difference in body weight was observed, in spite of the persistence of macroscopic and microscopic lesions and increased colon weight/length ratio. Supplementation with soluble fiber or FOS did not revert colon lesions or any of the study parameters. Supplementation with FOS, but not with fiber, was associated with increased colon weight/length ratio on the 14th day. CONCLUSION: Supplementation with soluble fiber or FOS produced no significant impact on TNBS-induced colitis in rats.

OBJETIVO: Avaliar a suplementação de fibra solúvel ou frutooligossacarídeos (FOS) na colite induzida por TNBS em ratos. MÉTODOS: Sessenta e quatro ratos Wistar receberam por gavagem água, fibra solúvel ou FOS. Após 14 dias, foram submetidos à indução de colite com TNBS. O grupo controle recebeu água por gavagem e por enema retal. Decorridos 7 ou 14 dias, após a avaliação do peso, os ratos foram sacrificados e o peso do colo, escores macroscópicos e microscópicos da lesão cólica foram aferidos. RESULTADOS: No 7° dia após indução da colite, houve uma significativa diminuição do peso dos ratos, um aumento do peso do cólon e lesão cólica macroscópica/microscópica. A suplementação com fibra ou FOS não reverteu nenhum destes parâmetros. No 14° dia após a indução da colite não foram observadas diferenças no peso dos ratos, entretanto houve uma persistência da lesão cólica macroscópica/microscópica e do aumento do peso do cólon. A suplementação com fibra ou FOS não reverteu à lesão cólica. A suplementação de FOS, mas não de fibra, aumentou o peso do colo comparado com o grupo colite no 14° dia. CONCLUSÃO: A suplementação com fibra solúvel ou com FOS não alterou a colite por TNBS em ratos.