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BackgroundPreclinical trials are essential to test efficacious options to substitute the temporomandibular joint (TMJ) disk. The contemporary absence of an ideal treatment for patients with severe TMJ disorders can be related to difficulties concerning the appropriate study design to conduct preclinical trials in the TMJ field. These difficulties can be associated with the use of heterogeneous animal models, the use of the contralateral TMJ as control, the absence of rigorous randomized controlled preclinical trials with blinded outcomes assessors, and difficulties involving multidisciplinary teams.ObjectiveThis study aims to develop a new, reproducible, and effective study design for preclinical research in the TMJ domain, obtaining rigorous data related to (1) identify the impact of bilateral discectomy in black Merino sheep, (2) identify the impact of bilateral discopexy in black Merino sheep, and (3) identify the impact of three different bioengineering TMJ discs in black Merino sheep.MethodsA two-phase exploratory randomized controlled preclinical trial with blinded outcomes is proposed. In the first phase, nine sheep are randomized into three different surgical bilateral procedures: bilateral discectomy, bilateral discopexy, and sham surgery. In the second phase, nine sheep are randomized to bilaterally test three different TMJ bioengineering disk implants. The primary outcome is the histological gradation of TMJ. Secondary outcomes are imaging changes, absolute masticatory time, ruminant time per cycle, ruminant kinetics, ruminant area, and sheep weight.ResultsPrevious preclinical studies in this field have used the contralateral unoperated side as a control, different animal models ranging from mice to a canine model, with nonrandomized, nonblinded and uncontrolled study designs and limited outcomes measures. The main goal of this exploratory preclinical protocol is to set a new standard for future preclinical trials in oromaxillofacial surgery, particularly in the TMJ field, by proposing a rigorous design in black Merino sheep. The authors also intend to test the feasibility of pilot outcomes. The authors expect to increase the quality of further studies in this field and to progress in future treatment options for patients undergoing surgery for TMJ disk replacement.ConclusionsThe study has commenced, but it is too early to provide results or conclusions.

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BackgroundMesenchymal stem/stromal cells have unique properties favorable to their use in clinical practice and have been studied for cardiac repair. However, these cells are larger than coronary microvessels and there is controversy about the risk of embolization and microinfarctions, which could jeopardize the safety and efficacy of intracoronary route for their delivery. The index of microcirculatory resistance (IMR) is an invasive method for quantitatively assessing the coronary microcirculation status.ObjectivesTo examine heart microcirculation after intracoronary injection of mesenchymal stem/stromal cells with the index of microcirculatory resistance.MethodsHealthy swine were randomized to receive by intracoronary route either 30x106 MSC or the same solution with no cells (1% human albumin/PBS) (placebo). Blinded operators took coronary pressure and flow measurements, prior to intracoronary infusion and at 5 and 30 minutes post-delivery. Coronary flow reserve (CFR) and the IMR were compared between groups.ResultsCFR and IMR were done with a variance within the 3 transit time measurements of 6% at rest and 11% at maximal hyperemia. After intracoronary infusion there were no significant differences in CFR. The IMR was significantly higher in MSC-injected animals (at 30 minutes, 14.2U vs. 8.8U, p = 0.02) and intragroup analysis showed a significant increase of 112% from baseline to 30 minutes after cell infusion, although no electrocardiographic changes or clinical deterioration were noted.ConclusionOverall, this study provides definitive evidence of microcirculatory disruption upon intracoronary administration of mesenchymal stem/stromal cells, in a large animal model closely resembling human cardiac physiology, function and anatomy.

The effect of vaginal administration of misoprostol plus terbutaline sulphate 6 h prior to artificial insemination (AI) upon the site of AI (vaginal or cervical) and fertility was studied using a total of 87 estrous synchronized Serra da Estrela ewes (control n = 42 and treated n = 45). Artificial insemination was performed using refrigerated semen at 54-55 h after sponge removal. Lambing rate (fertility) and prolificacy were compared between control and treated ewes. The effect of the site of semen deposition on fertility was also evaluated. Prolificacy rate was not different between control (1.5) and treated (1.59) ewes. The proportion of cervical AI achieved in control (45.2%) and treated (37.8%) ewes was not significantly different. Overall, fertility was significantly lower in control than in treated ewes (42.9% vs 64.4%; p < 0.04). Fertility following vaginal AI was significantly lower for control for than treated ewes (30.4% vs 60.7%; p < 0.03) but the difference was smaller and not significant for cervical AI (control 57.9% vs 70.6%). It was concluded that vaginal administration of misoprostol plus terbutaline sulphate 6 h prior to artificial insemination did not affect the proportion of cervical inseminations but significantly improved the fertility of treated ewes. Although needing confirmation, it was hypothesized that drugs might have induced local secretory modifications leading to an increase of cervical ability to retain more viable spermatozoa for fertilization.

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SUMMARYWe intend to estimate Saloia breed rams fertility and its variation coefficients (VC) after cervical artificial insemination (AI) with refrigerated (SR) or frozen semen (SC). In experiment 1, we studied the seasonal effect of AI (spring vs. autumn) on fertility (n=5 rams) using SR. The seasonal effect of semen freezing (autumn vs. winter, n=3 rams) on fertility of ewes inseminated in spring was also tested with SC. Variations in ram fertility using either SF or SC were determined independently of seasons of insemination and freezing (experiment 2: SF (n=4), SC (n=4), same rams; experiment 3: SF=16, FS=5 rams). No seasonal differences in fertility were found when ewes were inseminated either with SF or SC. Fertility was higher when RS rather than SC was used (experiment 2: 51.28 vs. 13.65 %; experiment 3: 48.51 vs. 13.04 %, respectively). Fertility VCs from SC were higher than those from SR (experiment 2: 41.3 vs. 13.1 %; experiment 3: 38.9 vs. 19.5 %, respectively). SR or SC from Saloia rams can be used in AI programs during the studied seasons with no deleterious effect on fertility. Higher fertility VCs are estimated when insemination is performed with SR, suggesting semen individual susceptibility to freezing. INTRODUÇÃOA IA com SC por via cervical origina fertilidades baixas, devido às alterações que ocorrem nos espermatozóides (spz) durante o processo de congelação/descongelação, responsáveis por maiores dificuldades no trânsito espermático, diminuição da capacidade fertilizante e aumento da mortalidade embrionária (Álvarez et al., 2012). Os primeiros resultados obtidos após IA com sémen congelado (SC) originaram uma