Multiparametric Comparison of Two TTA-Based Surgical Techniques in Dogs with Cranial Cruciate Ligament Tears.

Tearing of the cranial cruciate ligament causes hindlimb lameness in dogs. Different surgical procedures have been proposed to treat this condition. In this study, two different TTA-based techniques and implants were compared. A total of 30 dogs were separated into two groups according to the technique and implant used (Porous TTA® or Model Xgen®). The aim of the study was to assess whether one of these techniques has better functional recovery of the joint, better bone consolidation after the osteotomy procedure and fewer osteoarthritic changes. We compared both groups up to 3 months after surgery. No significant differences were found in any of the assessed parameters. Thus, both procedures were found to be equally effective and safe.

Neuroprotective effects of meloxicam on transient brain ischemia in rats: the two faces of anti-inflammatory treatments.

The inflammatory response plays an important role in neuroprotection and regeneration after ischemic insult. The use of non-steroidal anti-inflammatory drugs has been a matter of debate as to whether they have beneficial or detrimental effects. In this context, the effects of the anti-inflammatory agent meloxicam have been scarcely documented after stroke, but its ability to inhibit both cyclooxygenase isoforms (1 and 2) could be a promising strategy to modulate post-ischemic inflammation. This study analyzed the effect of meloxicam in a transient focal cerebral ischemia model in rats, measuring its neuroprotective effect after 48 hours and 7 days of reperfusion and the effects of the treatment on the glial scar and regenerative events such as the generation of new progenitors in the subventricular zone and axonal sprouting at the edge of the damaged area. We show that meloxicam's neuroprotective effects remained after 7 days of reperfusion even if its administration was restricted to the two first days after ischemia. Moreover, meloxicam treatment modulated glial scar reactivity, which matched with an increase in axonal sprouting. However, this treatment decreased the formation of neuronal progenitor cells. This study discusses the dual role of anti-inflammatory treatments after stroke and encourages the careful analysis of both the neuroprotective and the regenerative effects in preclinical studies.

Intralaboratory Validation of a Kinetic Turbidimetric Assay Based on Limulus Amebocyte Lysate (LAL) for Assessing Endotoxin Activity in Cow Milk.

Mastitis, one of the most common diseases in dairy cattle, causes severe losses in the dairy sector worldwide and affects animal welfare. The disease is characterized by an inflammatory reaction of the mammary gland and is mainly caused by bacterial infections, including both Gram-negative and Gram-positive bacteria. The release of endotoxins associated to bacterial lysis is a weighty factor in the clinical course of Gram-negative associated mastitis and should be taken into consideration when using antibiotics in the treatment of these infections. Therefore, endotoxin detection in milk samples would be of help in the management of bovine mastitis. With this aim, we have validated a kinetic turbidimetric assay based on Limulus amebocyte lysate (LAL) for the quantification of endotoxins in milk samples. The assay was adapted to this particular matrix by incorporating filtration and dilution of the milk samples in the procedure. Our results demonstrate the robustness and usefulness of the assay, which allows the identification of coliform mastitis in milk samples from affected cows and the quantification of endotoxin activity in bulk and commercial milk samples. Further studies are required to evaluate the performance of the assay in mastitis milk samples associated to Gram-negative bacteria other than Escherichia coli as well as during the clinical course of these Gram-negative mastitis or after their treatment with antibiotics.

Development of an Artificial Neural Network for the Detection of Supporting Hindlimb Lameness: A Pilot Study in Working Dogs.

Subjective lameness assessment has been a controversial subject given the lack of agreement between observers; this has prompted the development of kinetic and kinematic devices in order to obtain an objective evaluation of locomotor system in dogs. After proper training, neural networks are potentially capable of making a non-human diagnosis of canine lameness. The purpose of this study was to investigate whether artificial neural networks could be used to determine canine hindlimb lameness by computational means only. The outcome of this study could potentially assess the efficacy of certain treatments against diseases that cause lameness. With this aim, input data were obtained from an inertial sensor positioned on the rump. Data from dogs with unilateral hindlimb lameness and sound dogs were used to obtain differences between both groups at walk. The artificial neural network, after necessary adjustments, was integrated into a web management tool, and the preliminary results discriminating between lame and sound dogs are promising. The analysis of spatial data with artificial neural networks was summarized and developed into a web app that has proven to be a useful tool to discriminate between sound and lame dogs. Additionally, this environment allows veterinary clinicians to adequately follow the treatment of lame canine patients.

The role of morphometric and respiratory factors in predicting the severity and evolution of urinary symptoms in patients with obstructive sleep apnea syndrome.

OBJECTIVES: To assess the severity, evolution, and behaviour of several urinary symptoms in patients with obstructive sleep apnea syndrome (OSAS) before and after the treatment with continuous positive airway pressure (CPAP). METHODS: A prospective study was performed on patients with a recent diagnosis of sleep apnea confirmed by nocturnal sleep polygraphy and absence of medical urological past history. The symptom incidence was analysed seeking predictive factors for initial nocturia, nocturnal polyuria (NP), and unfavourable International Prostate Symptoms Score (IPSS) before and after a 1-year period of treatment using a CPAP device. Morphometric variables (body mass index, BMI; neck and abdominal diameter) and functional respiratory variables (FEV1, FVC, and FEV1/FVC) were analysed. A multivariate analysis was performed with a calculation of Pearson's correlation coefficient to establish a linear relation between the variables. RESULTS: A total of 43 patients completed the two-step study (IPSS and bladder diary before and after the CPAP treatment). IPSS decreased by 3.58 points. Nocturia decreased to once per night. Neck diameter, FEV1, and FEV1/FVC significantly predicted the initial severity of some lower urinary tract symptoms (LUTS), (p=0.015, p=0.029, p=0.008, respectively). Neck diameter, abdominal perimeter, and FEV1/FVC significantly predicted the LUTS evolution throughout the study (p=0.023, p=0.007, p=0.05, respectively). CONCLUSION: Some pre-treatment morphometry and spirometry parameters such as abdominal or neck diameter, FEV1, and FEV1/FVC were predictive of the severity and evolution of LUTS in patients with OSAS.

Multi-headed (bifid and trifid) mandibular condyles in archaeological contexts: Two posttraumatic cases.

OBJECTIVE: Bifid and trifid mandibular condyles are infrequent morphological alterations of the mandibular condyle. With the aim of better identifying its possible causing factors in the past and provide clues on the potential types and severities of joint dysfunction that may occur if clinical intervention is not undertaken, two archaeological cases of multi-headed mandibular condyles are presented, and their possible aetiology and pathogenesis are discussed. DESIGN: In this study, 143 adult mandibles recovered in the northwest of Spain were examined: 91 exhumed from San Juan Bautista church (Guardo, Palencia; 16th-19th centuries), and 52 from San Salvador de Palat de Rey church (León, 13th-19th centuries). All mandibles were observed macroscopically for the presence of any morphological and/or pathological alterations. When justified, the mandibles were also scrutinized through computed tomography. RESULTS: Two isolated mandibles (n = 1, Palencia; n = 1, León) with multi-headed mandibular condyles (bifid and trifid) were identified. The computed tomography scan of the affected mandibles revealed alterations compatible with traumatic events, namely line fractures and deformations at the angle of the mandible. CONCLUSIONS: Both the bifid and trifid mandibular condyles here described probably result from traumatic events during childhood leading to a posttraumatic deformation. Although no severe impairment of mandibular use was identified, some asymmetries probably resulted in some sort of malfunction, with TMJ-OA and gonial angle eversion as supporting evidence. Nevertheless, the degree of bone remodelling observed indicates that both individuals lived long after the traumatic occurrence.

Stafne's bone defects from Spain: report of four cases and brief archaeological literature review.

OBJECTIVE: To present for the first time in the north-western Spanish osteological record prevalence data on Stafne's bone defect, to compare the results with those reported by other studies, and to increase the dataset for future inter-population comparisons. MATERIAL: In all, 143 complete adult mandibles recovered from two necropolises were analyzed (n = 118, San Juan Bautista of Guardo, Palencia province, 16th-19th centuries; n = 25, Plaza del Grano, city of León, 12th-15th centuries). METHODS: Differential diagnosis of the lesions was made through macroscopic and Computed Tomography (CT) analyses. RESULTS: Four mandibles (n = 3, Guardo, Palencia; n = 1, León) presented bone cavities on the lingual aspect of the mandible below the mylohyoid channel, between the first molar and the angle of the mandible. CT scan showed unilateral well-defined unilocular oval/round concavities in the lingual mandibular cortex below the inferior alveolar canal. Neither the macroscopic nor the radiological characteristics are compatible with inflammatory or malignant pathology, favoring instead a diagnosis of Stafne's bone defect. CONCLUSIONS: Four cases of Stafne's defects are added to the bioarchaeological inventory. The calculated prevalence is 2.54% for San Juan Bautista and 4% for Plaza del Grano, values in close agreement to those presented in other osteoarchaeological studies. SIGNIFICANCE: The identification of all examples of Stafne's bone defects in past populations will contribute to elucidate which factors may be responsible for this trait's cultural, ecological, temporal, and geographical patterning. LIMITATIONS: The skeletal samples are relatively small. SUGGESTIONS FOR FURTHER RESEARCH: In future investigations of Stafne's bone defects, CT analysis of dry bone specimens is recommended, whenever possible.

Development and Evaluation of a Disease Large Animal Model for Preclinical Assessment of Renal Denervation Therapies.

New-generation catheters-based renal denervation (RDN) is under investigation for the treatment of uncontrolled hypertension (HTN). We assessed the feasibility of a large animal model of HTN to accommodate the human RDN devices. Ten minipigs were instrumented to measure blood pressure (BP) in an awake-state. HTN was induced with subcutaneous 11-deoxycorticosterone (DOCA, 100 mg/kg) implants. Five months after, the surviving animals underwent RDN with the Symplicity® system. Norepinephrine (NE) renal gradients were determined before and 1 month after RDN. Renal arteries were processed for histological (hematoxylin-eosin, Movat pentachrome) and immunohistochemical (S100, tyrosine-hydroxylase) analyses. BP significantly rose after DOCA implants. Six animals died prematurely, mainly from infectious causes. The surviving animals showed stable BP levels after 5 months. One month after RDN, nerve damage was showed in three animals, with impedance drop >10%, NE gradient drop and reduction in BP. The fourth animal showed no nerve damage, impedance drop <10%, NE gradient increase and no change in BP. In conclusion, the minipig model of DOCA-induced HTN is feasible, showing durable effects. High mortality should be addressed in next iterations of this model. RDN may partially offset the DOCA-induced HTN. Impedance drop and NE renal gradient could be markers of RDN success.

Incidence of obstetric anal sphincter injuries after implementing the Triepi-45 tool to improve episiotomy angle in instrumental deliveries.

OBJECTIVE: To assess the impact of Triepi-45-a tool that enables an episiotomy angle of 45° to be marked on the perineum at rest-on the incidence of obstetric anal sphincter injuries (OASIS) during operative vaginal delivery (OVD). METHOD: A retrospective-prospective cohort study was performed among successive women who underwent OVD at Complejo Asistencial Universitario de de León, Spain, between 2011 and 2013 (preintervention cohort, n=986) and between 2014 and 2016 (intervention cohort, n=986) after implementation of an interventional programme in 2013 to improve the episiotomy angle, including use of Triepi-45, in OVD. RESULTS: The intervention cohort had a lower incidence of OASIS than the preintervention cohort (70/986 [7.1%] vs 93/986 [9.4%]), but the difference was not significant, owing to the low use of Triepi-45 in the intervention cohort (n=375). However, the OASIS incidence was significantly lower in the Triepi-45 cohort than in the preintervention cohort (18/375 [4.8%] vs 93/986 [9.4%]; odds ratio, 0.47; 95% confidence interval, 0.26-0.86). CONCLUSION: Use of Triepi-45 had a positive impact on reducing OASIS in OVD. It remains essential to raise obstetricians' awareness of the importance of the episiotomy angle and to implement the systematic use of tools to reduce the incidence of OASIS.

Post-ischemic salubrinal administration reduces necroptosis in a rat model of global cerebral ischemia.

Ischemic stroke is one of the most important causes of death and disability worldwide. Subroutines underlying cell death after stroke are largely unknown despite their importance in the design of novel therapies for this pathology. Necroptosis, a recently described form of regulated cell death, has been related with inflammation and, in some models, with endoplasmic reticulum (ER) stress. We hypothesize that alleviation of ER stress following a salubrinal treatment will reduce the ischemic-dependent necroptosis. To probe the hypothesis, we measured, at 48 and 72 h after transient global cerebral ischemia in rat, in cerebral cortex and cornu ammonis 1, the main hallmarks of necroptosis: mRNA levels and phosphorylation of mixed lineage kinase domain like pseudokinase as well as receptor interacting serine/threonine protein kinase 3, along the years 2017-2018. Selective neuronal loss after 7 days of the ischemic insult, and other markers related with the inflammatory response were also measured. This study shows that necroptosis in cerebral cortex can be detected after 72 h of the insult and seems to be elicited before 48 h of reperfusion. The type of necroptosis here observed seems to be tumor necrosis factor receptor 1 independent. Necroptotic response is less evident in the cornu ammonis 1 hippocampal area than in cerebral cortex. The treatment with salubrinal administered 1 and 24 h after the ischemia, decreased the necroptotic marker levels and reduced the areas of selective neuronal loss, supporting the presence of ischemic-dependent necroptosis, and the notion that ER stress is involved in the necroptotic response. Open Science: This manuscript was awarded with the Open Materials Badge For more information see: https://cos.io/our-services/open-science-badges/.

Brain-derived neurotrophic factor alleviates the oxidative stress induced by oxygen and glucose deprivation in an ex vivo brain slice model.

Brain-derived neurotrophic factor (BDNF) is considered as a putative therapeutic agent against stroke. Since BDNF role on oxidative stress is uncertain, we have studied this role in a rat brain slice ischemia model, which allows BDNF reaching the neural parenchyma. Hippocampal and cerebral cortex slices were subjected to oxygen and glucose deprivation (OGD) and then returned to normoxic conditions (reperfusion-like, RL). OGD/RL increased a number of parameters mirroring oxidative stress in the hippocampus that were reduced by the BDNF presence. BDNF also reduced the OGD/RL-increased activity in a number of antioxidant enzymes in the hippocampus but no effects were observed in the cerebral cortex. In general, we conclude that alleviation of oxidative stress by BDNF in OGD/RL-exposed slices relies on decreasing cPLA2 activity, rather than modifying antioxidant enzyme activities. Moreover, a role for the oxidative stress in the differential ischemic vulnerability of cerebral cortex and hippocampus is also supported.

Which characteristics of the episiotomy and perineum are associated with a lower risk of obstetric anal sphincter injury in instrumental deliveries.

OBJETIVE: Operative vaginal delivery (OVD) is the most important risk fact for obstetric anal sphincter injury (OASI). Knowledge of possible risk factors for their occurrence may therefore reduce the likelihood of faecal incontinence. The aim is to analyse the effect of mediolateral episitomy and perineum characteristics on the occurrence of OASI in OVD. STUDY DESIGN: Case-control study, which included 958 OVD that were reviewed in Pelvic Floor and Puerperium Clinic. The episiotomy and perineum characteristics of those women who experienced OASIs (n = 150) were compared with those who had no evidence of anal sphincter injury (n = 788). RESULTS: In multivariate logistic regression analysis the factors which were independently associated were nulliparity, persistent occipitoposterior position, birthweight >3500 g, an angle of episiotomy <30°, a distance episiotomy-fourchette <5 mm and a distance of perineal body <30 mm. The analysis of subgroups show that only the multiparous women does not benefit from any feature of the episiotomy, and an angle greater than 30° and a distance episiotomy-fourchette >5 mm are associated with a risk reduction of OASI in nulliparous, perineal bodies ≤30 mm and occipitoanterior position. CONCLUSIONS: Two modifiable risk factors at the time of performing the episiotomy, the angle and distance episiotomy-fourchette, have been identified as the risk modification of OASI. It is necessary to achieve an adequate angle to reduce the probability of OASIs in OVD, and in nulliparous women with an anterior position and a distance of perineal body ≤30 mm could benefit from increasing the episiotomy-fourchette distance.

Seguridad y eficacia de nuevos modelos de stents liberadores de sirolimus con polímero biodegradable en el modelo preclínico / Safety and efficacy of new biodegradable polymer-based sirolimus-eluting stents in a preclinical model

Introducción y objetivos: Los nuevos stents farmacoactivos (SFA), diseñados para solventar las limitaciones de los existentes, han de someterse inicialmente al análisis preclínico. El objetivo es analizar la eficacia y la seguridad de nuevos SFA con polímero biodegradable en comparación con stents convencionales (SC) y SFA comercializados en el modelo de arteria coronaria sana porcina. Métodos: Se implantaron aleatoriamente 101 stents (SC y stents liberadores de sirolimus con polímero biodegradable: 3 formulaciones test [BD1, BD2 y BD3], Orsiro, Biomime y Biomatrix) en las arterias coronarias de 34 cerdos domésticos. Se completó estudio angiográfico e histomorfométrico al mes (n = 83) y a los 3 meses (n = 18). Resultados: Los stents se implantaron en proporción stent/arteria de 1,31 ± 0,21, sin diferencias entre grupos. Al mes, los nuevos stents (BD1, BD2 y BD3) mostraron menos pérdida tardía y reestenosis angiográfica, así como menor área neointimal y reestenosis histológica (p < 0,0005) que los SC. No se observaron diferencias significativas entre los nuevos stents y los SC en endotelización, daño vascular o inflamación; solo se encontró mayor persistencia de fibrina en los nuevos (p = 0,0006). A los 3 meses, todas estas diferencias desaparecieron, excepto una menor área neointimal con el nuevo stent BD1 (p = 0,027). No hubo diferencias en ningún parámetro al mes ni a los 3 meses entre los nuevos stents y los comercializados. Conclusiones: En este modelo preclínico, los nuevos SFA con polímero biodegradable estudiados presentan menos reestenosis que los SC, sin diferencias significativas en seguridad y eficacia respecto a SFA comercializados (AU)

Introduction and objectives New drug-eluting stents (DES) designed to overcome the limitations of existing devices should initially be tested in preclinical studies. Our objective was to analyze the safety and efficacy of new biodegradable polymer-based DES compared with bare-metal stents (BMS) and commercially available DES in a model of normal porcine coronary arteries. Methods: We randomly implanted 101 stents (BMS and biodegradable polymer-based sirolimus-eluting stents: 3 test stent iterations [BD1, BD2, and BD3], Orsiro, Biomime and Biomatrix) in the coronary arteries of 34 domestic pigs. Angiographic and histomorphometric studies were conducted 1 month (n = 83) and 3 months (n = 18) later. Results: The stents were implanted at a stent/artery ratio of 1.31 ± 0.21, with no significant differences between groups. At 1 month, the new test stents (BD1, BD2 and BD3) showed less late loss and angiographic restenosis, as well as lower histologic restenosis and neointimal area (P < .0005), than the BMS. There were no differences in endothelialization, vascular injury, or inflammation between the new test stents and BMS, although the new stents showed higher fibrin deposition (P = .0006). At 3 months, all these differences disappeared, except for a lower neointimal area with the new BD1 stent (P = .027). No differences at any time point were observed between the new test stents and commercially available controls. Conclusions: In this preclinical model, the new biodegradable polymer-based DES studied showed less restenosis than BMS and no significant differences in safety or efficacy vs commercially available DES (AU)

Safety and Efficacy of New Biodegradable Polymer-based Sirolimus-Eluting Stents in a Preclinical Model.

INTRODUCTION AND OBJECTIVES: New drug-eluting stents (DES) designed to overcome the limitations of existing devices should initially be tested in preclinical studies. Our objective was to analyze the safety and efficacy of new biodegradable polymer-based DES compared with bare-metal stents (BMS) and commercially available DES in a model of normal porcine coronary arteries. METHODS: We randomly implanted 101 stents (BMS and biodegradable polymer-based sirolimus-eluting stents: 3 test stent iterations [BD1, BD2, and BD3], Orsiro, Biomime and Biomatrix) in the coronary arteries of 34 domestic pigs. Angiographic and histomorphometric studies were conducted 1 month (n = 83) and 3 months (n = 18) later. RESULTS: The stents were implanted at a stent/artery ratio of 1.31 ± 0.21, with no significant differences between groups. At 1 month, the new test stents (BD1, BD2 and BD3) showed less late loss and angiographic restenosis, as well as lower histologic restenosis and neointimal area (P < .0005), than the BMS. There were no differences in endothelialization, vascular injury, or inflammation between the new test stents and BMS, although the new stents showed higher fibrin deposition (P = .0006). At 3 months, all these differences disappeared, except for a lower neointimal area with the new BD1 stent (P = .027). No differences at any time point were observed between the new test stents and commercially available controls. CONCLUSIONS: In this preclinical model, the new biodegradable polymer-based DES studied showed less restenosis than BMS and no significant differences in safety or efficacy vs commercially available DES.

The influence of Ringer's lactate or HES 130/0.4 administration on the integrity of the small intestinal mucosa in a pig hemorrhagic shock model under general anesthesia.

OBJECTIVE: To determine the effect of fluid resuscitation with 2 different physiological solutions, Ringer's lactate (RL) and hydroxyethyl starch (HES) 130/0.4, on histological lesions of the small intestinal mucosa in anesthetized pigs subjected to severe acute bleeding. DESIGN: Prospective experimental study. SETTING: University teaching hospital. ANIMALS: Twenty-eight healthy Large White pigs, 3 months of age. INTERVENTIONS: Pigs were subjected to severe acute bleeding (30 mL/kg) under total intravenous anesthesia with propofol and remifentanil. Pigs were randomly allocated to 3 groups: Group 1 (n = 11) received RL solution (25 mL/kg) after bleeding; Group 2 (n = 11) received HES 130/0.4 solution (20 mL/kg) after bleeding; and Group 3 (n = 6) volume replacement nor induced bleeding. Pigs were euthanized and the small intestine was harvested for histopathological analysis. MEASUREMENTS AND MAIN RESULTS: The small intestine was histologically evaluated and the presence of the following lesions were characterized: edema, congestion, hyperemia, hemorrhage, inflammatory infiltration, cellular degeneration, necrosis, and epithelial detachment. Mucosal loss percentage (%ML) and crypt:interstitium ratio (C:I) were also assessed. In the duodenum, jejunum, and ileum, and the entire small intestine, the %ML was significantly higher in Group 1, than in Groups 2 and 3. Hyperemia in the small intestine was significantly higher in pigs resuscitated with HES 130/0.4 compared to pigs resuscitated with RL. CONCLUSIONS AND CLINICAL RELEVANCE: In a setting of controlled hemorrhage, resuscitation with HES 130/0.4 was associated with a lower percentage of mucosal loss on the small intestine, compared with resuscitation with RL solution. Our study also suggests that the duodenum may be more sensitive to hypovolemia induced by severe hemorrhage.

Experimental evidence of pharmacological management of anchorage in Orthodontics: A systematic review.

INTRODUCTION: Orthodontic anchorage is one of the most challenging aspects of Orthodontics. Preventing undesired movement of teeth could result in safer and less complicated orthodontic treatment. Recently, several reviews have been published about the effects of different molecules on bone physiology and the clinical side effects in Orthodontics. However, the effects of local application of these substances on the rate of orthodontic tooth movement have not been assessed. OBJECTIVES: The aim of this research was to analyze the scientific evidence published in the literature about the effects of different molecules on orthodontic anchorage. METHODS: The literature was systematically reviewed using PubMed/Medline, Scopus and Cochrane databases from 2000 up to July 31st, 2014. Articles were independently selected by two different researchers based on previously established inclusion and exclusion criteria, with a concordance Kappa index of 0.86. The methodological quality of the reviewed papers was performed. RESULTS: Search strategy identified 270 articles. Twenty-five of them were selected after application of inclusion/exclusion criteria, and only 11 qualified for final analysis. Molecules involved in orthodontic anchorage were divided into three main groups: osteoprotegerin (OPG), bisphosphonates (BPs) and other molecules (OMs). CONCLUSIONS: Different drugs are able to alter the bone remodeling cycle, influencing osteoclast function and, therefore, tooth movement. Thus, they could be used in order to provide maximal anchorage while preventing undesired movements. OPG was found the most effective molecule in blocking the action of osteoclasts, thereby reducing undesired movements.

Experimental evidence of pharmacological management of anchorage in Orthodontics: A systematic review

Introduction: Orthodontic anchorage is one of the most challenging aspects of Orthodontics. Preventing undesired movement of teeth could result in safer and less complicated orthodontic treatment. Recently, several reviews have been published about the effects of different molecules on bone physiology and the clinical side effects in Orthodontics. However, the effects of local application of these substances on the rate of orthodontic tooth movement have not been assessed.Objectives: The aim of this research was to analyze the scientific evidence published in the literature about the effects of different molecules on orthodontic anchorage.Methods: The literature was systematically reviewed using PubMed/Medline, Scopus and Cochrane databases from 2000 up to July 31st, 2014. Articles were independently selected by two different researchers based on previously established inclusion and exclusion criteria, with a concordance Kappa index of 0.86. The methodological quality of the reviewed papers was performed.Results: Search strategy identified 270 articles. Twenty-five of them were selected after application of inclusion/exclusion criteria, and only 11 qualified for final analysis. Molecules involved in orthodontic anchorage were divided into three main groups: osteoprotegerin (OPG), bisphosphonates (BPs) and other molecules (OMs).Conclusions: Different drugs are able to alter the bone remodeling cycle, influencing osteoclast function and, therefore, tooth movement. Thus, they could be used in order to provide maximal anchorage while preventing undesired movements. OPG was found the most effective molecule in blocking the action of osteoclasts, thereby reducing undesired movements.

Introdução: a ancoragem ortodôntica é um dos aspectos mais desafiadores da Ortodontia. A prevenção de movimentos dentários indesejados poderia resultar em um tratamento ortodôntico mais seguro e menos complexo. Recentemente, foram publicadas várias revisões de literatura sobre os efeitos de diferentes substâncias na fisiologia do tecido ósseo e os efeitos colaterais clínicos na Ortodontia. Porém, os efeitos da aplicação local dessas substâncias no grau de movimentação dentária ortodôntica não foram avaliados.Objetivos: o objetivo da presente pesquisa foi analisar a evidência científica publicada na literatura sobre os efeitos de diferentes substâncias na ancoragem ortodôntica.Métodos: a literatura foi sistematicamente revisada utilizando-se as bases de dados PubMed/Medline, Scopus e Cochrane, de 2000 a 31 de julho de 2014. Os artigos foram selecionados, de maneira independente, por dois pesquisadores diferentes, tendo como base critérios de inclusão e exclusão previamente estabelecidos, com um índice Kappa de concordância de 0,86. A qualidade metodológica dos artigos revisados foi analisada.Resultados: a estratégia de pesquisa identificou 270 artigos; 25 artigos foram selecionados após a aplicação dos critérios de inclusão e exclusão, mas apenas 11 foram qualificados para a análise final. As substâncias envolvidas na ancoragem ortodôntica foram divididas em três grupos principais: osteoprotegerina (OPG), bisfosfonatos (BFs) e outras substâncias (OSs).Conclusões: diferentes substâncias são capazes de alterar o ciclo de remodelação óssea, influenciando na função dos osteoclastos e, portanto, na movimentação dentária. Sendo assim, essas substâncias podem ser utilizadas para promover o máximo de ancoragem e prevenir movimentos indesejados. A OPG foi a substância mais eficaz no bloqueio da ação dos osteoclastos, reduzindo os movimentos indesejados.

Age-dependent modifications in vascular adhesion molecules and apoptosis after 48-h reperfusion in a rat global cerebral ischemia model.

Stroke is one of the leading causes of death and permanent disability in the elderly. However, most of the experimental studies on stroke are based on young animals, and we hypothesised that age can substantially affect the stroke response. The two-vessel occlusion model of global ischemia by occluding the common carotid arteries for 15 min at 40 mmHg of blood pressure was carried out in 3- and 18-month-old male Sprague-Dawley rats. The adhesion molecules E- and P-selectin, cell adhesion molecules (CAMs), both intercellular (ICAM-1) and vascular (VCAM-1), as well as glial fibrillary acidic protein (GFAP), and cleaved caspase-3 were measured at 48 h after ischemia in the cerebral cortex and hippocampus using Western blot, qPCR and immunofluorescence techniques. Diametric expression of GFAP and a different morphological pattern of caspase-3 labelling, although no changes in the cell number, were observed in the neurons of young and old animals. Expression of E-selectin and CAMs was also modified in an age- and ischemia/reperfusion-dependent manner. The hippocampus and cerebral cortex had similar response patterns for most of the markers studied. Our data suggest that old and young animals present different time-courses of neuroinflammation and apoptosis after ischemic damage. On the other hand, these results suggest that neuroinflammation is dependent on age rather than on the different vulnerability described for the hippocampus and cerebral cortex. These differences should be taken into account in searching for therapeutic targets.

Histology and immunochemistry evaluation of autologous translocation of retinal pigment epithelium-choroid graft in porcine eyes.

PURPOSE: To evaluate structure and cellular functionality of retinal pigment epithelium (RPE)-choroid grafts after autologous translocation in porcine eyes. METHODS: Retinal pigment epithelium-choroid grafts were obtained from the nasal midperiphery donor site and translocated to the central area in 12 pigs (12 eyes). Grafts were placed under the central retina through a retinotomy. Ophthalmoscopic and pathological evaluations were performed immediately (n = 1) and at 15 (n = 3) and 30 (n = 3) days after surgery. Untranslocated nasal RPE-choroid grafts were obtained at time of surgery and used as controls. Specimens were evaluated by standard histology and by immunochemical studies of RPE65, CRALBP and GFAP. RESULTS: Five animals were lost to follow-up owing to surgery or anaesthesia complications. Ophthalmoscopic examination revealed that the grafts remained in place at all time-points studied. Fifteen and thirty days postsurgery, some areas of the transplanted RPE maintained a monolayered structure. Retinal pigment epithelium cells were firmly attached to Bruch's membrane and predominantly preserved polarity and pigment distribution. However, RPE65, CRALBP and GFAP patterns of expression and distribution were diminished and modified during follow-up. Ophthalmoscopic retinal detachment and proliferative vitreoretinopathy (PVR), confirmed by microscopic evaluation, complicated all cases at 30 days of follow-up. CONCLUSION: Autologous RPE-choroid grafts survived up to 30 days in porcine eyes. Histological and immunochemical evaluation revealed preserved transplanted RPE cells morphology accompanied by alterations in the immunoreactivity expression of functional proteins, and development of significant PVR. The data presented in this manuscript provide insights into the fate, viability and cellular functionality of the transplanted RPE-choroid graft, serving as foundation for further knowledge and improvement of this technique.