Efeito do fotossensibilizador butyl azul de toluidina na terapia fotodinâmica antimicrobiana para o tratamento da periodontite experimental em ratos / Effects of butyl toluidine blue photosensitizer on antimicrobial photodynamic therapy for experimental periodontitis treatment in rats

O presente estudo avaliou pela primeira vez "in vivo" os efeitos de três concentrações do butyl azul de toluidina (BuTB) como agente fotossensibilizador na terapia fotodinâmica antimicrobiana (aPDT), como terapia coadjuvante a raspagem e alisamento radicular (RAR), para o tratamento de periodontite experimental (PE) em ratos. A PE foi induzida por meio da instalação de um fio de algodão ao redor do primeiro molar inferior esquerdo. Posteriormente os animais foram aleatoriamente distribuídos em 7 grupos com 15 animais cada, através de uma tabela gerada por computador, de acordo com os seguintes tratamentos: RAR (n=15) - RAR seguido de irrigação local de solução salina fisiológica; BuTB-0,1 (n=15) - RAR seguido de aplicação local de BuTB na concentração de 0,1 mg/mL; aPDT-0,1 (n=15) - RAR seguido da aplicação local de BuTB na concentração de 0,1 mg/mL e irradiação com laser de diodo (LD) de InGaAlP (660 nm, 40 mW, 60 s, 2,4 J); BuTB-0,5 (n=15) ­ RAR seguido de aplicação local de BuTB na concentração de 0,5 mg/mL; aPDT-0,5 (n=15) ­ RAR seguido da aplicação local de BuTB na concentração de 0,5 mg/mL e irradiação com LD; BuTB-2,0 (n=15) - RAR seguido de aplicação local de BuTB na concentração de 2 mg/mL; aPDT-2,0 (n=15) - RAR seguido da aplicação local de BuTB na concentração de 2 mg/mL e irradiação com LD. Decorridos 7, 15 e 30 dias pós-tratamento, 5 animais de cada grupo foram submetidos à eutanásia. A área de furca dos molares foi submetida às análises histológica, histométrica e dos padrões de imunomarcação para TGF-ß1, OCN e TRAP. Os dados foram submetidos à análise estatística (α = 5%). De acordo com a análise histométrica na região de furca, todos os grupos experimentais apresentaram menor perda óssea comparado ao grupo controle. Histologicamente, os espécimes do aPDT-0,5 apresentaram uma resposta inflamatória local mais branda e menos extensa, com melhor reestruturação tecidual em todos os períodos. Aos 30 dias observou-se resolução total da resposta inflamatória local, com presença de tecido conjuntivo denso. Alguns espécimes apresentavam trabéculas ósseas com contorno regular revestido com osteoblastos ativos, incluindo áreas de neoformação óssea. O tratamento com aPDT na concentração de 0,5 mg/mL resultou em padrões mais altos de imunomarcação de TGF-ß1 em todos os períodos e de OCN aos 30 dias. Diante dos resultados obtidos, todas as concentrações do novo fotossensibilizador BuTB trouxeram resultados adicionais ao tratamento da PE em relação a RAR. No entanto, a aPDT realizada com a concentração de 0,5 mg/mL resultou em benefícios adicionais na resposta inflamatória local e melhor reestruturação tecidual(AU)

The present study evaluated for the first time the effects of three concentrations of butyl toluidine blue (BuTB) as a photosensitizing agent on antimicrobial photodynamic therapy (aPDT), as adjuvant therapy to scaling and root planing (SRP), for the treatment of experimental periodontitis (EP) in rats. EP was induced by placing a cotton thread around the lower left first molar. Subsequently, the animals were randomly distributed into seven groups with 15 animals each, through a computer generated table, according to the following treatments: SRP (n = 15), SRP followed by local irrigation of physiological saline solution; BuTB-0.1 (n = 15), SRP followed by local application of 0.1 mg/mL BuTB; aPDT-0.1 (n = 15), SRP followed by local application of BuTB at 0.1 mg/mL concentration and irradiation with InGaAlP diode laser (DL) (660 nm, 40 mW, 60 s, 4 J); BuTB-0.5 (n = 15), SRP followed by local application of BuTB at 0.5 mg/mL concentration; aPDT-0.5 (n = 15), SRP followed by local application of BuTB at 0.5 mg/mL concentration and DL irradiation; BuTB-2.0 (n = 15), SRP followed by local application of BuTB at 2 mg/mL concentration; aPDT-2.0 (n = 15), SRP followed by local application of BuTB at 2 mg/mL concentration and DL irradiation. The animals (n=5) from each group were submitted to euthanasia at 7, 15 and 30 days post-treatment. The furcation area of the first lower molar was submitted to histological, histometric and immunohistochemical analyses to identify TGF-ß1, OCN and TRAP. The data were submitted to statistical analysis (α = 5%). According to the histometric analysis in the furcation region, all experimental groups presented lower bone loss compared to the control group. Histologically, the aPDT -0.5 specimens presented a milder and less extensive local inflammatory response, with better tissue remodeling in all periods. Total resolution of the local inflammatory response was observed at 30 days with presence of mature connective tissue. Some specimens presented bone trabeculae with a regular contour and active osteoblasts, including areas of bone neoformation. Treatment with aPDT-0.5 also resulted in higher immunolabelling patterns of TGFß1 at all periods and of OCN at 30 days. All concentrations of the new photosensitizer BuTB resulted in significant improvement for EP treatment in relation to SRP. However, aPDT combined with BuTB at 0.5 mg / mL showed the best benefits for inflammatory response and periodontal repair process(AU)

Use of animal models of atrial fibrillation in the study of cellular and molecular therapy / 中国实验动物学报

Atrial fibrillation ( AF) is an abnormal heart rhythm characterised by rapid and irregular beating.It is caused by multiple factors and can lead to ischemia-associated thrombosis, heart failure and other complex symptoms. Based on the etiology and characteristics of AF, animal models have 3 main categories including electrical, neurohormonal or vessel-related, and structural remodeling models.New technologies such as microRNA knock-down/overexpression or CRISPR-Cas9 gene editing provide tools for constructing animal AF models and directions in the development of AF thera-peutic strategies.Currently these strategies have largely focused on the cellular and molecular therapeutics rather than tradi-tional invasive electrophysiological methods or antiarrhythmic drugs.With the aid of new tools, progress has been greatly made in a broad range of therapeutic research areas including molecular mechanisms, drug targeting and screening.This re-view summarizes the animal models of atrial fibrillation currently used in studies of the molecular and cellular therapeutics and notes their contributions to this research area.

The Effects of Lactobacillus rhamnosus on the Prevention of Asthma in a Murine Model

PURPOSE: Lactobacilli are probiotic bacteria that are effective in the management of allergic diseases or gastroenteritis. It is hypothesized that such probiotics have immunoregulatory properties and promote mucosal tolerance. Our goal was to investigate whether Lactobacillus casei rhamnosus Lcr35 could inhibit airway inflammation in an ovalbumin (OVA)-induced murine model of asthma. METHODS: BALB/c mice aged 6 weeks were used in the present study. Lactobacillus casei rhamnosus Lcr35 was administered daily, starting 1 week prior to the first OVA sensitization (group 1) and 2 days before the first 1% OVA airway challenge (group 2). Mice that received only saline at both sensitization and airway challenge time points were used as negative controls (group 3), and those that had OVA-induced asthma were used as positive controls (group 4). Airway responsiveness to methacholine was assessed, and bronchoalveolar lavage (BAL) was performed. At the endpoint of the study, total IgE as well as OVA-specific IgE, IgG1 and IgG2a in serum was measured by enzyme-linked immunosorbent assay. Lung pathology was also evaluated. RESULTS: Airway hyperresponsiveness, total cell counts and the proportion of eosinophils in BAL fluid were significantly decreased in group 1 compared with group 4 (P<0.05). Total serum IgE levels were also significantly decreased in group 1 compared with group 4. Serum levels of OVA-specific IgE, IgG1 and IgG(2a) were not significantly influenced by treatment with Lcr35. There was significantly less peribronchial and perivascular infiltration of inflammatory cells in group 1 compared with group 4; however, there were no significant differences in methacholine challenge, BAL, serology or histology between groups 2 and 4. CONCLUSIONS: Oral treatment with Lcr35 prior to sensitization can attenuate airway inflammation and hyperreactivity in a mouse model of allergic airway inflammation. These results suggest that Lcr35 may have potential for preventing asthma.

Antigen screening and identification of Helicobacter pylori outer membrane proteins from murine infection model / 中国免疫学杂志

Objective:To screen antigen of Helicobacter pylori outer membrane proteins by murine infection model.Methods:Parallel two-dimensional gel electrophoresis (2D) of outer membrane proteins extracted from Helicobacter pylori strain SS1 was performed.Western blot of a duplicate 2D gel hybridized with serum from H.pylori-infected murine was employed.Immunogenic H.pylori proteins identified in this way were digested in gel by trypsin and the mass of generated peptides were measured by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS).The data obtained from peptide mass finger-printing (PMF) were searched using the internet available database.Results:32 proteins were identified and they are in good agreement with typical protective antigens which reacted with serum from H.pylori-infected patients.Conclusion:The results suggest that murine model of H.pylori may be valid to screen antigens for human vaccination and the proteins identified in this paper are valuable for the selection of H.pylori protective antigens as well.

Histologic change of the posterior attachment in anterior disc displacement of the temporomandibular joint - a new model of internal derangement in rabbits / 대한치과교정학회지

This paper describes a new method to create an animal model for TMJ internal derangement in the New Zealand white rabbits and the light and electron microscopical changes of posterior attachment of them. Twenty six rabbits(2.5-3.0kg), four normal and twenty two experimental, were used. The right disc of experimental animal was displaced anteriorly without sectioning the posterior attachment and tied to the zygomatic arch with nylon not to be reduced to the original position. The left TMJ was sham-operated to be compared with its right experimental one. Normal animals were sacrificed one day and eight weeks after experiment. Experimental animals were sacrificed one day, ten days, three weeks, five weeks and eight weeks after surgery respectively. They were fixed intravenously with 2% glutaldehyde under general anesthesia and the samples of them were processed for light and electron microscopic examination. The purpose of this experiment is to make a suitable animal model of disc displacement without reduction for studying and understanding the cellular and morphologic events in posterior attachment of TMJ including early changes which were difficult to be observed in human TMJs. The results of this investigation suggest the following conclusions: 1. Authors induced anterior disc displacement surgically in rabbits with new method to examine histologic changes of posterior attachment. Tissue reactions of this model seem to be similar to those observed in human disc displacement. We think this animal model for anterior disc displacement may be used to explore and evaluate objectively the effects of many treatment modalities in disc displacements. 2. The animal disease model showed inflammation at early stage(one and ten days). At this stage there were mild-to-severe mononuclear inflammatory cell infiltration, numerous newly formed vessels, vessel dilatation and engormement and many fibroblasts. 3. At middle stage(three weeks), fibrosis occurred, where fibroblasts decreased in number, but their cytoplasm was profuse indicating high activity. Collagen fibers increased in number and the tissue looked more dense. 4. At late stage(five weeks and eight weeks) showed degenerative changes including perforation of posterior attachment, disintegration of collagen fiber bundles, degeneration of fibroblasts, metastatic ossification, and dystrophic calcification.

A new animal model of gastric cancer induced by MNNG's attacking combining ulcer / 中国药理学通报

AIM To establish a new animal model of gastric cancer with high incidence rate and short experimental period. METHODS Using N methyl N′ nitro N nitrasoguanidine(MNNG) combining ucler to induce rats to gastric cancer, taking the pathological situation of rats as the standard of canceration. RESULTS Six rats coming from model group were found as gastric cacinoma, the incidence rate of gastric cancer can reach forty percent. CONCLUSION This method can induce high incidence rate of gastric cancer during short experimental period. It deserves imroving and developing.

Hyperuricemia model induced by yeast in mice / 中国药理学通报

AIM To establish mice hyperuricemia model METHOD Yeast extract paste 7 5～30 g?kg -1 was given to mice by ig once daily for 7,14,21,28 consecutive days, and detected the level of uric acid in serum RESULT The serum uric acid level in mice were (271 8?53 2),(215 4?31 5),(195 9?56 0),(142 1?30 7) ?mol?L -1 in 30 g?kg -1 group after administration 1,2,3,4 weeks;and (226 8?40 7),(148 67?30 4),(176 9?27 0),(119 3?27 4) ?mol?L -1 in 15 g?kg -1 group after administration 1,2,3,4 weeks;In 7 5 g?kg -1 group the serum uric acid level was (117 0?29 0) ?mol?L -1 after 1 week, respectively CONCLUSION Yeast extract paste (15～30) g?kg -1 given by ig could form mice hyperuricemia model, and the hyperuricemia could last 1～2 weeks