Discussion and Concern on Animal Study for Orthopaedic Implantable Devices / 中国医疗器械杂志

In recent years, new orthopaedic implantable devices continue to emerge, which require higher requirements for technical evaluation. Animal study is an important part of the research and development process for the new orthopedic implantable devices, which provides relevant evidence for product design and stereotyping. By introducing the purpose of animal study, and the application of 3R principle (replacement, reduction, refinement) in this field, we summarize the concern on the animal study, in order to provide reference for the development and research of new orthopedic implantable devices and biomaterials. At the same time, the application of evidence-based research methods such as systematic review in the field is introduced, which provides new tools and approaches for the technical review and regulatory science.

Regulatory Consideration for Animal Study of Medical Device / 中国医疗器械杂志

Animal study plays a key role to evaluate the safety and effectivity of medical devices. This study aims to share evaluated consideration on the role, general principles, necessity, study design and quality management system of animal study, in order to improve the quality of animal study and reduce unnecessary study.

Anti-inflammatory effects of acupuncture in the treatment of chronic obstructive pulmonary disease / 中西医结合学报

Numerous randomised controlled trials have suggested the positive effects of acupuncture on chronic obstructive pulmonary disease (COPD). However, the underlying therapeutic mechanisms of acupuncture for COPD have not been clearly summarized yet. Inflammation is central to the development of COPD. In this review, we elucidate the effects and underlying mechanisms of acupuncture from an anti-inflammatory perspective based on animal studies. Cigarette smoke combined with lipopolysaccharide is often used to establish animal models of COPD. Electroacupuncture can be an effective intervention to improve inflammation in COPD, and Feishu (BL13) and Zusanli (ST36) can be used as basic acupoints in COPD animal models. Different acupuncture types can regulate different types of inflammatory cytokines; meanwhile, different acupuncture types and acupoint options have similar effects on modulating the level of inflammatory cytokines. In particular, acupuncture exerts anti-inflammatory effects by inhibiting the release of inflammatory cells, inflammasomes and inflammatory cytokines. The main underlying mechanism through which acupuncture improves inflammation in COPD is the modulation of relevant signalling pathways: nuclear factor-κB (NF-κB) (e.g., myeloid differentiation primary response 88/NF-κB, toll-like receptor-4/NF-κB, silent information regulator transcript-1/NF-κB), mitogen-activated protein kinase signalling pathways (extracellular signal-regulated kinase 1/2, p38 and c-Jun NH2-terminal kinase), cholinergic anti-inflammatory pathway, and dopamine D2 receptor pathway. The current synthesis will be beneficial for further research on the effect of acupuncture on COPD inflammation. Please cite this article as: Jiang LH, Li PJ, Wang YQ, Jiang ML, Han XY, Bao YD, Deng XL, Wu WB, Liu XD. Anti-inflammatory effects of acupuncture in the treatment of chronic obstructive pulmonary disease. J Integr Med. 2023; 21(6): 518-527.

Dental stem cells in intraoral regenerative therapy: a systematic review / Células-tronco dentárias na terapia regenerativa intraoral: uma revisão sistemática

Objective: 1) To critically review the published literature on applications of dental stem cells in the regeneration of intraoral tissues. 2) To provide an evidence-based level on research regarding application of dental stem cells in intraoral tissues regeneration. Methodology: This systematic review is conducted as per the JBI guidelines and reported as per the PRISMA. An initial literature search of papers published between 2004 and 2018 yielded 421 manuscripts. Nineteen studies satisfied the inclusion / exclusion criteria and were included for qualitative synthesis. Studies were categorized as animal (11) and human (8) trials. Five independent reviewers critically assessed the included studies. Risk of bias was assessed using SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) bias risk tool, robins-I tool for non-randomised clinical trial and Cochrane Collaboration's Tool for randomised clinical trial. Evidence levels were assessed based on JBI Criteria. Results: Animal trials mainly focused on periodontal regeneration. A high or unclear Risk of bias was more commonly found amongst animal studies. Laboratory, clinical and radiographic evaluation were used to assess the outcome. A total of Eight Human studies were conducted on a total samples size of 153 upon a wide age ranging from seven years to 60 years. Nearly 70% of the human studies used DPSC for regenerating alveolar bone defects. Conclusion: Appropriate well designed double-blind randomized clinical trials of longer duration are yet to be performed. Evidence for the included studies were 1C and 1D as per the JBI Criteria. Stem cell therapy demonstrated promising results in Periodontal tissue and alveolar bone regeneration. However, the number of studies to claim such a benefit are very limited (AU)

Objetivo: 1) Revisar criticamente a literatura publicada sobre aplicações de células-tronco dentárias na regeneração de tecidos intraorais. 2) Fornecer um nível baseado em evidências sobre pesquisas relacionadas à aplicação de células-tronco dentárias na regeneração de tecidos intraorais. Metodologia: Esta revisão sistemática é conduzida de acordo com as diretrizes do JBI e relatada de acordo com o PRISMA. Uma pesquisa bibliográfica inicial de artigos publicados entre 2004 e 2018 resultou em 421 manuscritos. Dezenove estudos satisfizeram os critérios de inclusão / exclusão e foram incluídos para síntese qualitativa. Os estudos foram categorizados como ensaios em animais (11) e humanos (8). Cinco revisores independentes avaliaram criticamente os estudos incluídos. O risco de viés foi avaliado usando a ferramenta de risco de viés do Centro de Revisão Sistemática para Experimentação com Animais de Laboratório (SYRCLE), a ferramenta robins-I para ensaios clínicos não randomizados e a Ferramenta da Colaboração Cochrane para ensaios clínicos randomizados. Os níveis de evidência foram avaliados com base nos critérios JBI. Resultados: Os ensaios em animais focaram principalmente na regeneração periodontal. Um risco alto ou pouco claro de viés foi mais comumente encontrado entre os estudos com animais. Avaliações laboratorial, clínica e radiográfica foram utilizadas para avaliar o resultado. Um total de oito estudos em humanos foram conduzidos em um tamanho total de amostras de 153 com ampla faixa etária, variando de sete a 60 anos. Quase 70% dos estudos em humanos usaram DPSC para regeneração de defeitos ósseos alveolares. Conclusão: Ensaios clínicos randomizados duplo-cegos apropriados e bem elaborados de maior duração ainda precisam ser realizados. As evidências para os estudos incluídos foram 1C e 1D de acordo com os critérios JBI. A terapia com células-tronco demonstrou resultados promissores na regeneração do tecido periodontal e do osso alveolar. No entanto, o número de estudos para reivindicar tal benefício é muito limitado (AU)

Effect of two corticotomy protocols on periodontal tissue and orthodontic movement

Abstract Objective To compare two corticotomy surgical protocols in rats to verify whether they alter conventional orthodontic movement. Methodology Sixty Wistar rats were divided into three groups - orthodontic movement (CG), orthodontic movement and corticotomy (G1) and orthodontic movement with corticotomy and decortication (G2) - and euthanized after 7 and 14 days. Tooth movement (mm), bone volume fraction and bone volume ratio to total volume (BV/TV), and bone mineral density (BMD) were evaluated by micro-CT. The total amount of bone was measured in square millimeters and expressed as the percentage of bone area in the histomorphometry. The number of positive TRAP cells and RANK/RANKL/OPG interaction were also investigated. Results Day 14 showed a statistically significant difference in orthodontic tooth movement in CG compared with G1 (7.52 mm; p=0.009) and G2 (7.36 mm; p=0.016). A micro-CT analysis revealed a difference between CG, G1 and G2 regarding BV/TV, with G1 and G2 presenting a lower BV/TV ratio at 14 days (0.77 and 0.73 respectively); we found no statistically significant differences regarding BMD. There was a difference in the total amount of bone in the CG group between 7 and 14 days. At 14 days, CG presented a significantly higher bone percentage than G1 and G2. Regarding TRAP, G2 had more positive cells at 7 and 14 days compared with CG and G1. Conclusion Corticotomy accelerates orthodontic movement. Decortication does not improve corticotomy efficiency.

Effect of Poly(Lactide-Co-Glycolide) Nanoparticles on Local Retention of Fluorescent Material: An Experimental Study in Mice

OBJECTIVE: Poly(lactide-co-glycolide) (PLGA) nanoparticles are promising materials for the development of new drug-releasing systems. The purpose of this study was to evaluate the in vivo retention time of materials loaded in nanoparticles as compared with that of the material alone by in vivo imaging in nude mice. MATERIALS AND METHODS: Mice (n = 20) were injected with 0.1 mL fluorescent material 1,1′-dioctadecyl-3,3,3′,3′ tetramethylindotricarbocyanine iodide (DiR)-loaded PLGA nanoparticles (200 nm) into the right paraspinal muscle, and the same volume of pure DiR solution was injected into the left paraspinal muscle. Fluorescence images were obtained using an in vivo optical imaging system. Fluorescent images were taken 1 day after the injection, and seven more images were taken at 1-week intervals. Image analysis was done with ImageJ program, and one region of interest was chosen manually, which corresponded to the highest signal-intensity area of fluorescence signal intensity. RESULTS: After 7 weeks, 12 mice showed a right-sided dominant signal, representing the DiR loaded PLGA nanoparticles; 5 mice showed a left-side dominant signal, representing the free DiR solution; and 3 mice showed no signal at all beginning 1 day after the injection. During the 7-week period, the mean signal intensities of the free DiR solution and DiR-loaded PLGA nanoparticles diverged gradually. On day 1, the mean signal intensity of free DiR solution was significantly higher than that of DiR-loaded PLGA (p < 0.001). Finally, by week 7, DiR-loaded PLGA express significantly high signal intensity compared with free DiR solution (p = 0.031). CONCLUSION: The results of the current study suggested that therapeutic agents bound to PLGA nanoparticles may exhibit prolonged retention times.

Ultrasound contrast-enhanced study as an imaging biomarker for anti-cancer drug treatment: preliminary study with paclitaxel in a xenograft mouse tumor model (secondary publication)

PURPOSE: The purpose of this study was to assess tumor angiogenesis using contrast-enhanced ultrasonography (CEUS) of human prostate cancer cells (PC3) that were implanted in mice before and after paclitaxel injection. METHODS: Twelve mice were injected with human PC3. The mice were grouped into two groups; one was the paclitaxel-treated group (n=6) and the other was the control group (n=6). Before administering paclitaxel into the peritoneal cavity, baseline CEUS was performed after the administration of 500 μL (1×108 microbubbles) of contrast agent. The area under the curve (AUC) up to 50 seconds after injection was derived from the time-intensity curves. After injection of paclitaxel or saline, CEUS studies were performed at the 1-week follow-up. Changes in tumor volume and the AUC in both two groups were evaluated. After CEUS, the microvessel density (MVD) was compared between the groups. RESULTS: In the paclitaxel-treated group, the AUC from CEUS showed a significant decrease 1-week after paclitaxel administration (P=0.030), even though the tumor volume showed no significant changes (P=0.116). In the control group, there was no significant decrease of the AUC (P=0.173). Pathologically, there was a significant difference in MVD between both groups (P=0.002). CONCLUSION: The AUC from the time intensity curve derived from CEUS showed an early change in response to the anti-cancer drug treatment that preceded the change in tumor size. The findings of CEUS could serve as an imaging biomarker for assessing tumor responses to anti-cancer drug treatment.

Osseointegration of Magnesium-Incorporated Sand-Blasted Acid-Etched Implant in the Dog Mandible: Resonance Frequency Measurements and Histomorphometric Analysis

The aim of this pilot study was to investigate the bone responses of novel magnesium (Mg)–incorporated sand-blasted and acid-etched (SLA) titanium (Ti) implant in an experimental animal model. Novel Mg-incorporated SLA Ti implant was obtained via vacuum arc source ion implantation method and Mg-ions were implanted into the SLA implant surface. Control group consisted of two commercial implants; resorbable blasting media (RBM) and SLA. Twelve implants from each group were placed into the mandibles of 6 mongrel dogs. Experimental animals were divided into 2 groups of 3 animals, with 4 weeks and 8 weeks healing time points. Resonance frequency analysis was performed at the time of fixture installation, 1, 2, 4, and 8 weeks after installation. Bone to implant contact (BIC) measurements were assessed at the 4 and 8 weeks healing time points. The overall implant survival rate was 97.2%. The Mg-incorporated SLA Ti implants showed more rapid osseointegration than control group implants at follow-up periods of 4 weeks. Histomorphometric analysis showed a tendency for BIC% values of Mg-incorporated SLA Ti implant to be higher than that of other the implant groups. The results of this study suggest that Mg-incorporated SLA Ti implant may be effective in enhancing the bone responses by rapid osseointegration in early healing periods.

Therapeutic Effects of Microbubbles Added to Combined High-Intensity Focused Ultrasound and Chemotherapy in a Pancreatic Cancer Xenograft Model

OBJECTIVE: To investigate whether high-intensity focused ultrasound (HIFU) combined with microbubbles enhances the therapeutic effects of chemotherapy. MATERIALS AND METHODS: A pancreatic cancer xenograft model was established using BALB/c nude mice and luciferase-expressing human pancreatic cancer cells. Mice were randomly assigned to five groups according to treatment: control (n = 10), gemcitabine alone (GEM; n = 12), HIFU with microbubbles (HIFU + MB, n = 11), combined HIFU and gemcitabine (HIGEM; n = 12), and HIGEM + MB (n = 13). After three weekly treatments, apoptosis rates were evaluated using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay in two mice per group. Tumor volume and bioluminescence were monitored using high-resolution 3D ultrasound imaging and in vivo bioluminescence imaging for eight weeks in the remaining mice. RESULTS: The HIGEM + MB group showed significantly higher apoptosis rates than the other groups (p < 0.05) and exhibited the slowest tumor growth. From week 5, the tumor-volume-ratio relative to the baseline tumor volume was significantly lower in the HIGEM + MB group than in the control, GEM, and HIFU + MB groups (p < 0.05). Despite visible distinction, the HIGEM and HIGEM + MB groups showed no significant differences. CONCLUSION: High-intensity focused ultrasound combined with microbubbles enhances the therapeutic effects of gemcitabine chemotherapy in a pancreatic cancer xenograft model.

The efficacy of traditional Chinese medicin in animal model of lung injury induced by paraquat: a Meta-analysis / 中华危重病急救医学

Objective To systematically review the effect of traditional Chinese medicine (TCM) in an animal model of lung injury induced by paraquat (PQ),and to provide a theoretical basis for future clinical trials.Methods The Wanfang,CNKI,VIP,PubMed/MEDLINE,EMBASE database (from January 1979 to September 2012) were searched.All papers concerning TCM in animal model of lung injury induced by PQ were retrieved.Study selection and data extraction were performed on the basis of Cochrane systematic review methods.Weighted mean difference (WMD) and 95％ confidence interval (95％CI) with random effects model was adopted to investigate the effect of TCM on lung injury induced by PQ.Results Eighteen papers involving 1 188 rats met our criteria.Meta-analysis showed that TCM could improve the lung coefficiency (WMD-0.07,95％ CI-0.14 to-0.01,P=0.03),reduce lung wet/dry weight ratio (WMD-1.15,95％CI-2.03 to-0.27,P=0.01),increase the serum superoxide dismutase (SOD) activity (WMD 56.08,95％CI 23.46 to 88.70,P=0.000 8),improve plasma glutathione peroxidase (GSH-Px) level (WMD 26.64,95％CI 18.95 to 34.33,P＜0.000 01),and lower serum malondialdehyde(MDA) level (WMD-0.65,95％CI-1.00 to-0.30,P=0.000 2),however there was no significant difference in the level of serum tumor necrosis factor-α (TNF-α) and hydroxyproline (HYP) level between TCM and controls (TNF-α:WMD-25.15,95％CI-54.87 to 4.57,P=0.10; HYP:WMD-0.11,95％CI-2.71 to 0.48,P=0.17).Conclusions These findings demonstrate the efficacy of TCM in animal models of lung injury induced by PQ.However taking account of heterogeneity,the efficacy should be interpreted with caution.

Reconstrução imediata de diferentes defeitos peri-implantares em implantes pós-exodônticos: análise histomorfométrica em cães / Reconstruction of buccal different defects at implants placed immediately into extraction sockets: a histomorphometric analysis in dogs

Objetivo: A proposta deste estudo foi avaliar a regeneração óssea de defeitos criados cirurgicamente e naturais circunferenciais (gap) de implantes pósexodônticos. Materiais e método: Para este estudo foram utilizados 8 cães da raça labrador, nos quais foram instalados implantes imediatos (pós-exodônticos) nos alvéolos dos dentes P2 (2o pré-molar) e M1 (1o molar) inferiores bilaterais. Nos implantes da região dos 2º pré-molares bilaterais foram criados cirurgicamente defeitos peri-implantares vestibulares que foram preenchidos de um lado por osso autógeno – OA e do outro por osso bovino inorgânico Bio-Oss®- OB. Nos alvéolos correspondentes aos primeiros molares (M1) os implantes foram instalados e os gaps (defeitos naturais) existente entre a tábua óssea vestibular e o implante, foram preenchidos por Bone Ceramic® - (grupo BC) ou somente coágulo (grupo COA). Todos os sítios cirúrgicos foram posteriormente recobertos por membrana de colágeno reabsorvível (Biogide ®) e mantidos com cicatrizador. Após 4 meses de pós-operatório, os animais foram eutanasiados e os blocos ósseos processados laboratorialmente para análise histomorfométrica. Resultados: Os resultados obtidos nos implantes instalados na região do P2 mostraram que os valores do IS-C foram ligeiramente maior (2.3±0.8mm) no grupo OA, comparado ao grupo OB (1.7± 0.7 mm), enquanto o IS-B dos grupos OA e OB foram respectivamente de 2.7±0.7mm e 2.2±1.0 mm no lado vestibular e de 1.6±0.8mm e 0.8±0.5mm no lado lingual. As médias dos valores de PM-C, PM-B e PM-IS no grupo OA e OB foram respectivamente de 4.3±0.9mm, 4.7±0.9mm, 2.0±1.6mm e 4.3±0.6mm, 4.8±0.6mm, 2.5±0.8mm. A diferença estatística significativa foi observada somente na espessura da crista óssea vestibular de 2 a 5 mm em direção ao IS (“pescoço do implante”), incluindo o biomaterial (S-OCbt) que se apresentou maior no grupo OB. Nos implantes instalados na região do M1, o gap vestibular horizontal foi de 1.1 (COA) e 1.4 mm (BC) e vertical de 3 e...

Objective: The purpose of these studies were to evaluate bone regeneration at natural or surgically-created buccal defects at implants placed immediately into extraction sockets (IPIES). Material and methods: Eight Labrador dogswere used and implants were placed immediately into the extraction sockets of P2 (second premolar) and M1 (first molar), bilaterally. At P2, the buccal wall of the extraction sockets was removed bilaterally to create a standardized defect, 4 mm wide coronally, 2 mm wide apically, and 6 mm height. At P2 sites, Bio-Oss at the test (OB) or autogenous bone at the control (OA) sites were used to fill the defects. At M1 sites, Bone Ceramic ® at the test (BC) or the clot alone (COA) were used to fill the defects. All surgical sites were subsequently covered by a resorbable collagen membraneand a non-submerged healing was allowed. After 4 months the animals were euthanized, bone blocks harvested and processed for histomorphometric analysis. Results: at P2 sites, IS- C values were slightly higher (2.3±0.8mm) in the OA compared to the OB (1.7±0.7 mm). IS- B were 2.7 ± 0.7mm and 2.2 ± 1.0mm on the buccal side and 1.6 ± 0.8mm and 0.8 ± 0.5mm on the lingual side at OA and OB groups, respectively. The average values of PM- C , B - PM and PM -IS in OA and OB groups were 4.3 ± 0.9mm , 4.7 ± 0.9mm , 2.0 ± 1.6mm and 4.3 ± 0.6mm , 4.8 ± 0.6mm , 2.5 ± 0.8mm, respectively. A statistically significant difference was only observed in the thickness of the buccal bony crest at 2-5 mm apically to IS (the implant neck) when the biomaterial (S -OCbt) was included in the measurement, which appeared to be higher in the OB group. At M1 sites, at the time of installation, the horizontal buccal gap was 1.1 at the COA and 1.4 mm at the BC sites while the vertical remaining defect was 3 mm and 4 mm deep in the control and test sites, respectively. At the buccal aspect, IS-C was higher in the COA (0.6 ± 1.6mm) compared to the BC (0.1 ± 1.8mm) groups and IS- B was...

Reconstrução imediata de diferentes defeitos peri-implantares em implantes pós-exodônticos: análise histomorfométrica em cães / Reconstruction of buccal different defects at implants placed immediately into extraction sockets: a histomorphometric analysis in dogs

Objetivo: A proposta deste estudo foi avaliar a regeneração óssea de defeitos criados cirurgicamente e naturais circunferenciais (gap) de implantes pósexodônticos. Materiais e método: Para este estudo foram utilizados 8 cães da raça labrador, nos quais foram instalados implantes imediatos (pós-exodônticos) nos alvéolos dos dentes P2 (2o pré-molar) e M1 (1o molar) inferiores bilaterais. Nos implantes da região dos 2º pré-molares bilaterais foram criados cirurgicamente defeitos peri-implantares vestibulares que foram preenchidos de um lado por osso autógeno – OA e do outro por osso bovino inorgânico Bio-Oss®- OB. Nos alvéolos correspondentes aos primeiros molares (M1) os implantes foram instalados e os gaps (defeitos naturais) existente entre a tábua óssea vestibular e o implante, foram preenchidos por Bone Ceramic® - (grupo BC) ou somente coágulo (grupo COA). Todos os sítios cirúrgicos foram posteriormente recobertos por membrana de colágeno reabsorvível (Biogide ®) e mantidos com cicatrizador. Após 4 meses de pós-operatório, os animais foram eutanasiados e os blocos ósseos processados laboratorialmente para análise histomorfométrica. Resultados: Os resultados obtidos nos implantes instalados na região do P2 mostraram que os valores do IS-C foram ligeiramente maior (2.3±0.8mm) no grupo OA, comparado ao grupo OB (1.7± 0.7 mm), enquanto o IS-B dos grupos OA e OB foram respectivamente de 2.7±0.7mm e 2.2±1.0 mm no lado vestibular e de 1.6±0.8mm e 0.8±0.5mm no lado lingual. As médias dos valores de PM-C, PM-B e PM-IS no grupo OA e OB foram respectivamente de 4.3±0.9mm, 4.7±0.9mm, 2.0±1.6mm e 4.3±0.6mm, 4.8±0.6mm, 2.5±0.8mm. A diferença estatística significativa foi observada somente na espessura da crista óssea vestibular de 2 a 5 mm em direção ao IS (“pescoço do implante”), incluindo o biomaterial (S-OCbt) que se apresentou maior no grupo OB. Nos implantes instalados na região do M1, o gap vestibular horizontal foi de 1.1 (COA) e 1.4 mm (BC) e vertical de 3 e...

Objective: The purpose of these studies were to evaluate bone regeneration at natural or surgically-created buccal defects at implants placed immediately into extraction sockets (IPIES). Material and methods: Eight Labrador dogswere used and implants were placed immediately into the extraction sockets of P2 (second premolar) and M1 (first molar), bilaterally. At P2, the buccal wall of the extraction sockets was removed bilaterally to create a standardized defect, 4 mm wide coronally, 2 mm wide apically, and 6 mm height. At P2 sites, Bio-Oss at the test (OB) or autogenous bone at the control (OA) sites were used to fill the defects. At M1 sites, Bone Ceramic ® at the test (BC) or the clot alone (COA) were used to fill the defects. All surgical sites were subsequently covered by a resorbable collagen membraneand a non-submerged healing was allowed. After 4 months the animals were euthanized, bone blocks harvested and processed for histomorphometric analysis. Results: at P2 sites, IS- C values were slightly higher (2.3±0.8mm) in the OA compared to the OB (1.7±0.7 mm). IS- B were 2.7 ± 0.7mm and 2.2 ± 1.0mm on the buccal side and 1.6 ± 0.8mm and 0.8 ± 0.5mm on the lingual side at OA and OB groups, respectively. The average values of PM- C , B - PM and PM -IS in OA and OB groups were 4.3 ± 0.9mm , 4.7 ± 0.9mm , 2.0 ± 1.6mm and 4.3 ± 0.6mm , 4.8 ± 0.6mm , 2.5 ± 0.8mm, respectively. A statistically significant difference was only observed in the thickness of the buccal bony crest at 2-5 mm apically to IS (the implant neck) when the biomaterial (S -OCbt) was included in the measurement, which appeared to be higher in the OB group. At M1 sites, at the time of installation, the horizontal buccal gap was 1.1 at the COA and 1.4 mm at the BC sites while the vertical remaining defect was 3 mm and 4 mm deep in the control and test sites, respectively. At the buccal aspect, IS-C was higher in the COA (0.6 ± 1.6mm) compared to the BC (0.1 ± 1.8mm) groups and IS- B was...

The Effects of Neutralization Therapy for Acute Alkali Ingestion in Rabbits

PURPOSE: To evaluate temperature changes in the gastric lumen and the efficacy of weak acid neutralization against the ingestion of a strong alkaline commercial agent. METHODS: A total of 23 male New Zealand White rabbits were anesthetized with an intramuscular injection of ketamine and xylazine. After gastric lavage, anoro-gastric catheter and an electric thermometer probe were inserted into the stomach. Then 3 mL/kg of room-temperature (24~26degrees C) 1M sodium hydroxide (NaOH) disinfectant was instilled into the gastric lumen. The rabbits were divided into three groups: Group 1 (n=8) was treated with NaOH only and Group 2 (n=7) and Group 3 (n=8) were treated with 39 mL/kg of room-temperature orange juice or water after 5 minutes, respectively. Intra-gastric temperature was continuously measured and compared with arterial pH before alkali insult and 30 minutes later. Gastric pH was measured, and pathological examination of the esophagus, stomach, and duodenum performed after animal sacrifice. RESULTS: Gastric lumen temperatures gradually increased from 32.6degrees C to 38.7degrees C after alkali instillation. Significant decreases in lumen temperature, 7.5degrees C or 12.0degrees C, were observed following treatment with water or orange juice, respectively (p<0.01). Post-treatment temperature did not exceed pre-treatment temperature for the entire observation period. The gastric pH of the neutralization group was much lower than the alkali alone group or the dilution group (7.0+/-0.7 vs. 11.6+/-0.2, or 10.6+/-0.4, respectively, mean+/-SD, p<0.01). In gastric microscopic findings, only mucosal injuries were observed in the neutralization groups, while there were no significant differences among groups in terms of esophageal or duodenal injury. CONCLUSION: Neutralization therapy with room-temperature orange juice for acute gastrointestinal injuries caused by liquid alkali did not cause additional thermal injury and might have protective effects against local tissue destruction in the stomach.

Percutaneous Transforaminal Epidural Injection Method in an Experimental Rat: Minimally Invasive Drug Delivery Method to Spinal Epidural Space

OBJECTIVE: To compare a newly developed minimally-invasive method for percutaneous transforaminal epidural injection (INJ group) with the existing method for lumbar epidural catheterization (CATH group). METHOD: Through anatomical review of experimental rats, the cephalic one fourth of the neural foramen was selected as the target point for drug delivery. After the rats had undergone lumbar epidural catheterization, lidocaine, and 1% methylene blue were injected through the unilateral or bilateral L5/6 neural foramen in the INJ group, and through an epidural catheter in the CATH group. Measurement of body weight and the mechanical allodynia test before and after injection of lidocaine, and fine dissection after injection were performed. RESULTS: Results of the mechanical allodynia test of 1.0% lidocaine 50 microl injection in the CATH group were statistically similar to those of 0.5% lidocaine 100 microl injection in the INJ group. The results of 2.0% lidocaine 50 microl injection in the CATH group were statistically similar to those of 1.0% lidocaine 100 microl injection in the INJ group. After dissection, only one distal partial spinal nerve was stained by methylene blue 50 microl through the transforaminal pathway. However, the dorsal root ganglion, nerve root, and adjacent hemi-partial spinal cord were stained by methylene blue 100 microl through the transforaminal pathway. CONCLUSION: The percutaneous transforaminal epidural injection is practical, easy, and safe, and, in particular, does not cause significant pain compared to the existing lumbar epidural catheterization. We expect this method to be effective in an animal study showing that drug delivery to the spinal epidural space is necessary.

US Contrast Enhanced Study as an Imaging Biomarker of Anti-cancer Drug Treatment: Preliminary Study with Paclitaxel and a Xenograft Mouse Tumor Model

PURPOSE: We wanted to assess tumor angiogenesis of human prostate cancer cells (PC3) implanted in mice before and after paclitaxel injection via contrast-enhanced ultrasonography (CEUS). MATERIALS AND METHODS: Twelve mice were injected with human prostate cancer cells (PC3) on the back or hind limbs. The mice were grouped into two groups; one was the paclitaxel treated group (n = 6) and the other was the control group, which was treated with normal saline (n = 6). Before injection of paclitaxel into the peritoneal cavity, baseline CEUS was performed by the administration of 500 microl (1x108 microbubbles) of contrast agent. The area under the curve (AUC) up to 50 seconds after contrast injection was derived from the time-intensity curves. After injection of paclitaxel or saline, one week follow up CEUS studies were performed. The changes of the tumor volume and the AUC in both two groups were evaluated. After CEUS, the mice were sacrificed and the microvessel density (MVD) was compared. RESULTS: In the paclitaxel treated group, the AUC from CEUS showed a significant decrease one week after paclitaxel administration (p = 0.03), even though the tumor volume showed no significant changes (p = 0.116). In the control group, there was no significant decrease of the AUC (p = 0.173). Pathologically, there was a significant difference of microvessel density in both groups (p = 0.002). CONCLUSION: The AUC from the time intensity curve derived from CEUS showed early change in response to the anti-cancer drug treatment in advance of a tumor size response. The findings of CEUS could be an imaging biomarker for assessing the tumor response to anti-cancer drug treatment.

Influência de implantes pós-exodônticos com diferentes configurações sobre os tecidos peri-implantares: estudo experimental em cães / Influence of implants with different configurations installed immediately into extraction sockets on peri-implant tissues: an experimental study in dogs

Objetivo: avaliar a influência da instalação de implantes em alvéolos imediatamente após a extração do elemento dental na regeneração dos tecidos peri-implantares com implantes de diferentes configurações Material e métodos: Nos alvéolos distais dos quartos pré-molares mandibulares de cães, imediatamente após as extrações das raízes dentais, foram instalados implantes cilíndricos com 3,3 mm de diâmetro (grupo controle) e implantes cônicos com 5,0 mm de diâmetro (grupo teste). Foram avaliados histologicamente a regeneração dos tecidos duros e moles peri-implantares após 4 meses do procedimento cirúrgico. Resultados: Todos os implantes apresentaram-se osseointegrados ao tecido ósseo maduro mineralizado. A crista óssea alveolar sofreu reabsorção tanto no grupo teste como controle. A superfície óssea vestibular dos implantes do grupo teste (cônico; 3,6 mm) apresentou maior grau de reabsorção em comparação ao grupo controle (cilíndrico; 1,6 mm). As dimensões dos tecidos moles apresentaram-se semelhantes em ambos os grupos. No entanto, em relação ao ombro do implante, a mucosa peri-implantar localizou-se mais apicalmente no grupo teste em relação ao grupo controle. Conclusão: Este estudo confirmou que a distância entre a superfície do implante e o contorno externo da crista óssea alveolar vestibular influenciou no grau de reabsorção da tábua óssea vestibular. Consequentemente, em relação ao ombro do implante, a mucosa peri-implantar será estabelecida em um nível mais apical, se a distância entre a superfície do implante e o contorno externo da crista óssea alveolar for menor

Aim: the aim of the present experiment was to study the influence of implant installation into sockets immediately after tooth extraction on the healing periimplant tissues with implants of various configurations. Material & methods: Transmucosal cylindrical 3.3mm in diameter implants in the control sites, and conical 5.0mm in diameter in the test sites, were installed into the distal socket of the forth mandibular premolars in dogs immediately after tooth extraction. After 4 months, the hard and soft tissue healing was evaluated histologically. Results: All implants were integrated in mineralized mature bone. Both at the test and control sites, the alveolar crest underwent resorption. The buccal bony surface at the implant of the test sites (conical; 3.6mm) was more resorbed compared to the control sites (cylindrical; 1.6mm). The soft tissue dimensions were similar in both groups. However, in relation to the implant shoulder, the periimplant mucosa was located more apically at the test compared to the control sites. Conclusion: The present study confirmed that the distance between the implant surface and the outer contour of the buccal alveolar bony crest influenced the degree of resorption of the buccal bone plate. Consequently, in relation to the implant shoulder, the peri-implant mucosa will be established at a more apical level if the distance between the implant surface and the outer contour of the alveolar crest is small

Avaliação do padrão de reparação óssea ao redor de implantes submersos: estudo experimental em cães / Bone healing pattern around submerged implants: an experimental study in dogs

Objetivo: estudar as fases iniciais da regeneração óssea de implantes instalados sobre a crista óssea alveolar desdentada. Material e Métodos: Em 12 cães labradores, foram extraídos bilateralmente todos os pré-molares inferiores e primeiros molares. Após 3 meses de regeneração, foi realizada a incisão sobre o rebordo alveolar desdentado do lado direito da mandíbula e descolamento do retalhos de espessura total. Foram instalados dois implantes e finalizado com a suturas dos retalhos para permitir a regeneração totalmente submersa. Posteriormente, foram realizados os mesmos procedimentos experimentais no lado esquerdo da mandíbula. Os sacrifícios dos animais foram planejados de forma a obter biópsias com pós-operatórios de 5, 10, 20 e 30 dias. Um implante de cada lado da mandíbula foi processado laboratorialmente para cortes histológicos em tecido mineralizado (inclusão em resina) e outro para cortes histológicos em tecido desmineralizado (inclusão em parafina). Resultados: Foi observada apenas uma reação celular importante ao redor do implante no compartimento da medula óssea. Observou-se a formação de matriz óssea provisória e, posteriormente, osso esponjoso ao redor e em contato com o implante. O contato osso-implante melhorou durante os períodos de regeneração avaliados. Conclusão: Com este estudo pode-se mostrar que a preparação do sítio cirúrgico e a instalação do implante produziram reação celular evidente no osso circunjacente. No compartimento da medula óssea, a aposição de matriz óssea provisória e formação de osso esponjoso ocorreram sequencialmente durante o primeiro mês de pós- operatório. Na região em que o osso apresentou contato com a superfície do implante, os processos de remodelação óssea (reabsorção e aposição óssea) ocorreram através da intervenção das BMUs (Bone Multicellular Units)

Objective: the purpose of the present study was to evaluate the early phases of bone response to implants installed in edentulous alveolar bony crest. Material & Method: In 12 Labrador dogs, all mandibular premolars and first molars were extracted bilaterally. After 3 months of healing, full-thickness flaps were elevated in the edentulous region of the right side of the mandible. Two implants were installed and the flaps were sutured to allow a fully-submerged healing. The experimental procedures were subsequently performed in the left side of the mandible. The timing of the experiments and sacrifices were planned in such a way to obtain biopsies representing the healing after 5, 10, 20, 30 days. One implant from each side of the mandible was processed for ground sections and the other for paraffin sections. Results: only an important cellular reaction was observed around the implant in the bone marrow compartment. Provisional matrix and, subsequently, woven bone were formed around and in contact with the implant. Bone-to-implant contact improve duign the healing period. Conclusions: In conclusion, the present experiment showed that site preparation and implant placement produced an evident cellular reaction within the surrounding bone. In the bone marrow compartment, provisional matrix apposition and woven bone formation occurred sequentially during the first month of healing. Where mineralized bone was in contact with the implant surface, bone remodeling processes (bone resorption and apposition) occurred through the intervention of BMUs (Bone Multicellular Units)

Efeito da plataforma Switching sobre os tecidos peri-implantares: estudo experimental em cães / Effect of plataform Switching on peri-implant tissues: an experimental study in dogs

Objetivo: Avaliar a influência da plataforma Switching sobre a remodelação dos tecidos peri-implantares. Material e métodos: Em 6 cães labradores, foram extraídos os pré-molares e primeiro molares inferiores bilateralmente. Após 3 meses de cicatrização, na região correpondente ao 1º molar, foi instalado um implante cônico em cada lado da mandíbula, com o ombro do mesmo posicionado ao nível da crista óssea alveolar vestibular. No lado direito da mandíbula, foi utilizado um pilar de diâmetro reduzido em relação à plataforma do implante, criando uma incompatibilidade de 0,85 milímetros (grupo teste), enquanto no lado esquerdo selecionou-se um pilar do mesmo diâmetro da plataforma do implante (grupo controle). Os retalhos foram suturados permitindo a cicatrização não-submersa. Após 4 meses, os animais foram eutanasiados para obtenção dos cortes histológicos para avaliação histométrica. Resultados: Todos os implantes apresentaram-se completamente osseointegrados. No grupo teste foram observados que os níveis ósseos apresentaram-se superiores ao grupo controle. No entanto, a diferença estatisticamente significativa foi encontrada apenas na região vestibular e na região proximal. A dimensão vertical dos tecidos moles foi maior no grupo controle em comparação ao grupo teste. No entanto, foi encontrada diferença estatisticamente significativa apenas na vestibular. Conclusões: O presente estudo demonstrou diferenças nas dimensões dos tecidos duros e moles peri-implantares (vestibular e proximal) como resultado da incompatibilidade do implante / pilar de 0,85 milímetros, quando o ombro do implante foi posicionado ao nível da crista óssea vestibular.

Aim: to evaluate the effect of platform switching on the peri-implant tissue remodeling. Material & methods: Mandibular premolars and first molars of 6 Labrador dogs were extracted bilaterally. After 3 months of healing, 1 tapered implant was installed on each side of the mandibular molar region with the implant shoulder placed at the level of the alveolar buccal bony crest. On the right side of the mandible, an abutment of reduced diameter in relation to the platform of the implant was used creating a mismatch of 0.85mm (test), while an abutment of the same diameter of the implant platform was affixed in the left side of the mandible (control). The flaps were sutured to allow a non-submerged healing. After 4 months, the animals were sacrificed and ground sections were obtained for histometric assessment. Results: All implants were completely osseointegrated. Bone levels were superior at the test than at the control sites. However, statistically significant differences were found only at the buccal and proximal aspects. The soft tissue vertical dimension was higher at the control compared to the test sites. However, statistically significant differences were demonstrated only or at the buccal aspects. Conclusions: The present study demonstrated differences in peri-implant (buccal and proximal) hard and soft tissue dimensions as a result of an implant/abutment mismatch of 0.85mm, when the implant shoulder was placed at the level of the buccal bony crest.

Influência de implantes pós-exodônticos com diferentes configurações sobre os tecidos peri-implantares: estudo experimental em cães / Influence of implants with different configurations installed immediately into extraction sockets on peri-implant tissues: an experimental study in dogs

Objetivo: avaliar a influência da instalação de implantes em alvéolos imediatamente após a extração do elemento dental na regeneração dos tecidos peri-implantares com implantes de diferentes configurações Material e métodos: Nos alvéolos distais dos quartos pré-molares mandibulares de cães, imediatamente após as extrações das raízes dentais, foram instalados implantes cilíndricos com 3,3 mm de diâmetro (grupo controle) e implantes cônicos com 5,0 mm de diâmetro (grupo teste). Foram avaliados histologicamente a regeneração dos tecidos duros e moles peri-implantares após 4 meses do procedimento cirúrgico. Resultados: Todos os implantes apresentaram-se osseointegrados ao tecido ósseo maduro mineralizado. A crista óssea alveolar sofreu reabsorção tanto no grupo teste como controle. A superfície óssea vestibular dos implantes do grupo teste (cônico; 3,6 mm) apresentou maior grau de reabsorção em comparação ao grupo controle (cilíndrico; 1,6 mm). As dimensões dos tecidos moles apresentaram-se semelhantes em ambos os grupos. No entanto, em relação ao ombro do implante, a mucosa peri-implantar localizou-se mais apicalmente no grupo teste em relação ao grupo controle. Conclusão: Este estudo confirmou que a distância entre a superfície do implante e o contorno externo da crista óssea alveolar vestibular influenciou no grau de reabsorção da tábua óssea vestibular. Consequentemente, em relação ao ombro do implante, a mucosa peri-implantar será estabelecida em um nível mais apical, se a distância entre a superfície do implante e o contorno externo da crista óssea alveolar for menor

Aim: the aim of the present experiment was to study the influence of implant installation into sockets immediately after tooth extraction on the healing periimplant tissues with implants of various configurations. Material & methods: Transmucosal cylindrical 3.3mm in diameter implants in the control sites, and conical 5.0mm in diameter in the test sites, were installed into the distal socket of the forth mandibular premolars in dogs immediately after tooth extraction. After 4 months, the hard and soft tissue healing was evaluated histologically. Results: All implants were integrated in mineralized mature bone. Both at the test and control sites, the alveolar crest underwent resorption. The buccal bony surface at the implant of the test sites (conical; 3.6mm) was more resorbed compared to the control sites (cylindrical; 1.6mm). The soft tissue dimensions were similar in both groups. However, in relation to the implant shoulder, the periimplant mucosa was located more apically at the test compared to the control sites. Conclusion: The present study confirmed that the distance between the implant surface and the outer contour of the buccal alveolar bony crest influenced the degree of resorption of the buccal bone plate. Consequently, in relation to the implant shoulder, the peri-implant mucosa will be established at a more apical level if the distance between the implant surface and the outer contour of the alveolar crest is small

Avaliação do padrão de reparação óssea ao redor de implantes submersos: estudo experimental em cães / Bone healing pattern around submerged implants: an experimental study in dogs

Objetivo: estudar as fases iniciais da regeneração óssea de implantes instalados sobre a crista óssea alveolar desdentada. Material e Métodos: Em 12 cães labradores, foram extraídos bilateralmente todos os pré-molares inferiores e primeiros molares. Após 3 meses de regeneração, foi realizada a incisão sobre o rebordo alveolar desdentado do lado direito da mandíbula e descolamento do retalhos de espessura total. Foram instalados dois implantes e finalizado com a suturas dos retalhos para permitir a regeneração totalmente submersa. Posteriormente, foram realizados os mesmos procedimentos experimentais no lado esquerdo da mandíbula. Os sacrifícios dos animais foram planejados de forma a obter biópsias com pós-operatórios de 5, 10, 20 e 30 dias. Um implante de cada lado da mandíbula foi processado laboratorialmente para cortes histológicos em tecido mineralizado (inclusão em resina) e outro para cortes histológicos em tecido desmineralizado (inclusão em parafina). Resultados: Foi observada apenas uma reação celular importante ao redor do implante no compartimento da medula óssea. Observou-se a formação de matriz óssea provisória e, posteriormente, osso esponjoso ao redor e em contato com o implante. O contato osso-implante melhorou durante os períodos de regeneração avaliados. Conclusão: Com este estudo pode-se mostrar que a preparação do sítio cirúrgico e a instalação do implante produziram reação celular evidente no osso circunjacente. No compartimento da medula óssea, a aposição de matriz óssea provisória e formação de osso esponjoso ocorreram sequencialmente durante o primeiro mês de pós- operatório. Na região em que o osso apresentou contato com a superfície do implante, os processos de remodelação óssea (reabsorção e aposição óssea) ocorreram através da intervenção das BMUs (Bone Multicellular Units)

Objective: the purpose of the present study was to evaluate the early phases of bone response to implants installed in edentulous alveolar bony crest. Material & Method: In 12 Labrador dogs, all mandibular premolars and first molars were extracted bilaterally. After 3 months of healing, full-thickness flaps were elevated in the edentulous region of the right side of the mandible. Two implants were installed and the flaps were sutured to allow a fully-submerged healing. The experimental procedures were subsequently performed in the left side of the mandible. The timing of the experiments and sacrifices were planned in such a way to obtain biopsies representing the healing after 5, 10, 20, 30 days. One implant from each side of the mandible was processed for ground sections and the other for paraffin sections. Results: only an important cellular reaction was observed around the implant in the bone marrow compartment. Provisional matrix and, subsequently, woven bone were formed around and in contact with the implant. Bone-to-implant contact improve duign the healing period. Conclusions: In conclusion, the present experiment showed that site preparation and implant placement produced an evident cellular reaction within the surrounding bone. In the bone marrow compartment, provisional matrix apposition and woven bone formation occurred sequentially during the first month of healing. Where mineralized bone was in contact with the implant surface, bone remodeling processes (bone resorption and apposition) occurred through the intervention of BMUs (Bone Multicellular Units)