617 research outputs found

    Cytotoxicity comparison of 2 bulk fill resin-composites

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    Poster presented at the CED-IADR/NOF Oral Health Research Congress (2017 Continental European and Scandinavian Divisions Meeting). September 21-23, 2017, Vienna, Austria.N/

    Effects of three current provisional restoration materials on fibroblast viability

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    Poster presented at the First international Congress of CiiEM - From Basic Sciences to Clinical Research. Egas Moniz, Caparica, Portugal, 27-28 November 2015Egas Moniz Cooperativa de Ensino Superior CR

    Cytotoxic and genotoxic effects of three cements used in fixed prosthesis

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    Poster presented at the First international Congress of CiiEM - From Basic Sciences to Clinical Research. Egas MOniz, Caparica, Portugal, 27-28 November 2015Egas Moniz - Cooperativa de Ensino Superior CR

    Blood Supply to the Integument of the Abdomen of the Rat: A Surgical Perspective

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    BACKGROUND: Many fundamental questions regarding the blood supply to the integument of the rat remain to be clarified, namely the degree of homology between rat and humans. The aim of this work was to characterize in detail the macro and microvascular blood supply to the integument covering the ventrolateral aspect of the abdominal wall of the rat. METHODS: Two hundred five Wistar male rats weighing 250-350 g were used. They were submitted to gross anatomical dissection after intravascular colored latex injection (n = 30); conversion in modified Spalteholz cleared specimens (n=10); intravascular injection of a Perspex solution, and then corroded, in order to produce vascular corrosion casts of the vessels in the region (n = 5); histological studies (n = 20); scanning electron microscopy of vascular corrosion casts (n = 10); surgical dissection of the superficial caudal epigastric vessels (n = 100); and to thermographic evaluation (n = 30). RESULTS: The ventrolateral abdominal wall presented a dominant superficial vascular system, which was composed mainly of branches from the superficial caudal epigastric artery and vein in the caudal half. The cranial half still received significant arterial contributions from the lateral thoracic artery in all cases and from large perforators coming from the intercostal arteries and from the deep cranial epigastric artery. CONCLUSIONS: These data show that rats and humans present a great deal of homology regarding the blood supply to the ventrolateral aspect of the abdominal integument. However, there are also significant differences that must be taken into consideration when performing and interpreting experimental procedures in rats.info:eu-repo/semantics/publishedVersio

    Design and Mechanism of (S)-3-Amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic Acid, a Highly Potent γ-Aminobutyric Acid Aminotransferase Inactivator for the Treatment of Addiction

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    © 2018 American Chemical Society. γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system. Inhibition of GABA aminotransferase (GABA-AT), a pyridoxal 5′-phosphate (PLP)-dependent enzyme that degrades GABA, has been established as a possible strategy for the treatment of substance abuse. The raised GABA levels that occur as a consequence of this inhibition have been found to antagonize the rapid release of dopamine in the ventral striatum (nucleus accumbens) that follows an acute challenge by an addictive substance. In addition, increased GABA levels are also known to elicit an anticonvulsant effect in patients with epilepsy. We previously designed the mechanism-based inactivator (1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (2), now called CPP-115, that is 186 times more efficient in inactivating GABA-AT than vigabatrin, the only FDA-approved drug that is an inactivator of GABA-AT. CPP-115 was found to have high therapeutic potential for the treatment of cocaine addiction and for a variety of epilepsies, has successfully completed a Phase I safety clinical trial, and was found to be effective in the treatment of infantile spasms (West syndrome). Herein we report the design, using molecular dynamics simulations, synthesis, and biological evaluation of a new mechanism-based inactivator, (S)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid (5), which was found to be almost 10 times more efficient as an inactivator of GABA-AT than CPP-115. We also present the unexpected crystal structure of 5 bound to GABA-AT, as well as computational analyses used to assist the structure elucidation process. Furthermore, 5 was found to have favorable pharmacokinetic properties and low off-target activities. In vivo studies in freely moving rats showed that 5 was dramatically superior to CPP-115 in suppressing the release of dopamine in the corpus striatum, which occurs subsequent to either an acute cocaine or nicotine challenge. Compound 5 also attenuated increased metabolic demands (neuronal glucose metabolism) in the hippocampus, a brain region that encodes spatial information concerning the environment in which an animal receives a reinforcing or aversive drug. This multidisciplinary computational design to preclinical efficacy approach should be applicable to the design and improvement of mechanism-based inhibitors of other enzymes whose crystal structures and inactivation mechanisms are known

    ABO-Incompatible Liver Transplantation in Acute Liver Failure: A Single Portuguese Center Study

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    INTRODUCTION: ABO-incompatible liver transplantation (ABOi LT) is considered to be a rescue option in emergency transplantation. Herein, we have reported our experience with ABOi LT including long-term survival and major complications in these situations. PATIENT AND METHODS: ABOi LT was performed in cases of severe hepatic failure with imminent death. The standard immunosuppression consisted of basiliximab, corticosteroids, tacrolimus, and mycophenolate mofetil. Pretransplantation patients with anti-ABO titers above 16 underwent plasmapheresis. If the titer was above 128, intravenous immunoglobulin (IVIG) was added at the end of plasmapheresis. The therapeutic approach was based on the clinical situation, hepatic function, and titer evolution. A rapid increase in titer required five consecutive plasmapheresis sessions followed by administration of IVIG, and at the end of the fifth session, rituximab. RESULTS: From January 2009 to July 2012, 10 patients, including 4 men and 6 women of mean age 47.8 years (range, 29 to 64 years), underwent ABOi LT. At a mean follow-up of 19.6 months (range, 2 days to 39 months), 5 patients are alive including 4 with their original grafts. One patient was retransplanted at 9 months. Major complications were infections, which were responsible for 3 deaths due to multiorgan septic failure (2 during the first month); rejection episodes (4 biopsy-proven of humoral rejections in 3 patients and 1 cellular rejection) and biliary. CONCLUSION: The use of ABOi LT as a life-saving procedure is justifiable in emergencies when no other donor is available. With careful recipient selection close monitoring of hemagglutinins and specific immunosuppression we have obtained acceptable outcomes

    Optimization of an Arterialized Venous Fasciocutaneous Flap in the Abdomen of the Rat

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    BACKGROUND: Although numerous experimental models of arterialized venous flaps (AVFs) have been proposed, no single model has gained widespread acceptance. The main aim of this work was to evaluate the survival area of AVFs produced with different vascular constructs in the abdomen of the rat. METHODS: Fifty-three male rats were divided into 4 groups. In group I (n = 12), a 5-cm-long and 3-cm-wide conventional epigastric flap was raised on the left side of the abdomen. This flap was pedicled on the superficial caudal epigastric vessels caudally and on the lateral thoracic vein cranially. In groups II, III, and IV, a similar flap was raised, but the superficial epigastric artery was ligated. In these groups, AVFs were created using the following arterial venous anastomosis at the caudal end of the flap: group II (n = 13) a 1-mm-long side-to-side anastomosis was performed between the femoral artery and vein laterally to the ending of the superficial caudal epigastric vein. In group III (n = 14), in addition to the procedure described for group II, the femoral vein was ligated medially. Finally, in group IV (n = 14), the superficial caudal epigastric vein was cut from the femoral vein with a 1-mm-long ellipse of adjacent tissue, and an end-to-side arterial venous anastomosis was established between it and the femoral artery. RESULTS: Seven days postoperatively, the percentage of flap survival was 98.89 ± 1.69, 68.84 ± 7.36, 63.84 ± 10.38, 76.86 ± 13.67 in groups I-IV, respectively. CONCLUSION: An optimized AVF can be produced using the vascular architecture described for group IV.info:eu-repo/semantics/publishedVersio

    Uma variante do gene WNK4 está associada à osteoporose mas não à hipertensão na população portuguesa

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    Germline mutations in the WNK4 gene originate Gordon syndrome or pseudohypoaldosteronism type II, a familial form of hypertension with hyperkalemia and hypercalciuria. The WNK4 protein encodes a protein kinase involved in the regulation of various renal ion channels. In order to elucidate the contribution of WNK4 genetic variants to hypertension and/or osteoporosis, we analyzed 271 control individuals and a cohort of 448 hypertensive and 372 osteoporosis patients from the Portuguese population. Ten genetic variants were detected in 4.3% of the population under study, none of which revealed any significant association to the hypertension phenotype. In contrast, a rare missense alteration in a highly conserved arginine residue in exon 17 showed an association to the osteoporosis group. Our data suggest that WNK4 polymorphism rs56116165 is a rare allelic variant of a candidate gene with a biological function in renal calcium homeostasis and thus may contribute to a genetic predisposition to osteoporosis.FC

    A Model of Free Tissue Transfer: The Rat Epigastric Free Flap

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    Free tissue transfer has been increasingly used in clinical practice since the 1970s, allowing reconstruction of complex and otherwise untreatable defects resulting from tumor extirpation, trauma, infections, malformations or burns. Free flaps are particularly useful for reconstructing highly complex anatomical regions, like those of the head and neck, the hand, the foot and the perineum. Moreover, basic and translational research in the area of free tissue transfer is of great clinical potential. Notwithstanding, surgical trainees and researchers are frequently deterred from using microsurgical models of tissue transfer, due to lack of information regarding the technical aspects involved in the operative procedures. The aim of this paper is to present the steps required to transfer a fasciocutaneous epigastric free flap to the neck in the rat. This flap is based on the superficial epigastric artery and vein, which originates from and drain into the femoral artery and vein, respectively. On average the caliber of the superficial epigastric vein is 0.6 to 0.8 mm, contrasting with the 0.3 to 0.5 mm of the superficial epigastric artery. Histologically, the flap is a composite block of tissues, containing skin (epidermis and dermis), a layer of fat tissue (panniculus adiposus), a layer of striated muscle (panniculus carnosus), and a layer of loose areolar tissue. Succinctly, the epigastric flap is raised on its pedicle vessels that are then anastomosed to the external jugular vein and to the carotid artery on the ventral surface of the rat's neck. According to our experience, this model guarantees the complete survival of approximately 70 to 80% of epigastric flaps transferred to the neck region. The flap can be evaluated whenever needed by visual inspection. Hence, the authors believe this is a good experimental model for microsurgical research and training.info:eu-repo/semantics/publishedVersio
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