Lanthanum carbonate, like sevelamer-HCl, retards the progression of vascular calcification and atherosclerosis in uremic apolipoprotein E-deficient mice

Atherosclerosis and vascular calcification (VC) progression in chronic kidney disease is favored by disturbances of mineral metabolism. We compared the effect of phosphate binder lanthanum (La) carbonate with sevelamer-HCl on atherosclerosis, VC and bone structure and function in mice with chronic renal failure (CRF). Apolipoprotein E-deficient (apoE(-/-)) mice were randomized to one non-CRF and three CRF groups, fed with standard diet (one non-CRF and one CRF) or diet supplemented with either 3% lanthanum carbonate (La3%) or 3% sevelamer-HCl (Sev3%). Both La3% and Sev3% supplemented CRF mice displayed a decrease of serum phosphorus, calcification at both intimal and medial aortic sites and atherosclerosis. This was associated with a reduction of plaque Type I collagen expression by both binders and of positive nitrotyrosine staining in response to sevelamer-HCl only. Increased mineral apposition and bone formation rates in unsupplemented CRF mice were reduced by Sev3% but not by La3%. The beneficial effects of La carbonate and sevelamer-HCl on the progression of VC and atherosclerosis in CRF mice could be mainly due to a decrease in phosphate retention and likewise a reduction of arterial Type I collagen expression. The effect of La carbonate differed from that of sevelamer-HCl in that it did not appear to exert its vascular effects via changes in oxidative stress or bone remodeling in the present model.

Newly forming bone graft: a novel surgical approach to the treatment of denuded roots

Many techniques have been proposed for root coverage. However, none of them presents predictable results in deep and wide recessions. Objective: The aim of this case series report is to describe an alternative technique for root coverage at sites showing deep recessions and attachment loss >4 mm at buccal sites. Material and Methods: Four patients presenting deep recession defects at buccal sites (>= 4 mm) were treated by the newly forming bone graft technique, which consists in the creation of an alveolar socket at edentulous ridge and transferring of granulation tissue present in this socket to the recession defect after 21 days. Clinical periodontal parameters, including recession depth (RD), probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), plaque index (PI) and keratinized gingiva width (KGW) were evaluated by a single examiner immediately before surgery and at 1, 3, 6 and 9 months postoperatively. Results: All cases showed reduction in RD and PD, along with CAL gain, although no increase in KGW could be observed. These findings suggest that the technique could favor periodontal regeneration along with root coverage, especially in areas showing deep recessions and attachment loss.

MUSCLE HEMANGIOMATOSIS PRESENTING AS A SEVERE FEATURE IN A PATIENT WITH THE PTEN MUTATION: EXPANDING THE PHENOTYPE OF VASCULAR MALFORMATIONS IN BANNAYAN-RILEY-RUVALCABA SYNDROME

Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare autosomal, dominantly-inherited, hamartoma syndrome with distinct phenotypic features. Mutations in the PTEN gene have been identified in PTEN hamartoma tumor syndromes. Our aim was to determine the correlation of phenotype-genotype relationships in a BRRS case. We have evaluated a PTEN mutation in a patient with vascular anomalies and the phenotypic findings of BRRS. We described an 8-year-old girl with the clinical features of BRRS, specifically with vascular anomalies. The mutation in the PTEN gene was identified by DNA sequencing. In our patient, we defined a de novo nonsense R335X (c. 1003 C>T) mutation in exon 8, which results in a premature termination codon. Due to vascular anomalies and hemangioma, the patient's left leg was amputated 1 year after the hemangioma diagnosis. Bannayan - Riley - Ruvalcaba syndrome patients with macrocephaly and vascular anomalies should be considered for PTEN mutation analysis and special medical care.

Tomographic, Histological, and Immunohistochemical Evidences on the Use of N-Butyl-2-Cyanoacrilate for Onlay Graft Fixation in Rabbits

Background: The bone tissue responses to Cyanoacrylate have been described in the literature, but none used N-butyl-2-cyanoacrilate (NB-Cn) for bone graft fixation. Purpose: The aims of the study were: (a) to analyze the bone grafts volume maintenance fixed either with NB-Cn or titanium screw; (b) to assess the incorporation of onlay grafts on perforated recipient bed; and (c) the differences of expression level of tartrate-resistant acid phosphatase (TRAP) protein involved in bone resorption. Materials and Methods: Eighteen New Zealand White rabbits were submitted to calvaria onlay grafting on both sides of the mandible. On one side, the graft was fixed with NB-Cn, while on the other hand the bone graft was secured with an osteosynthesis screw. The computed tomography (CT) was performed just after surgery and at animals sacrifice, after 1 (n = 9) and 6 weeks (n = 9), in order to estimate the bone grafts volume along the experiments. Histological sections of the grafted areas were prepared to evaluate the healing of bone grafts and to assess the expression of TRAP protein. Results: The CT scan showed better volume maintenance of bone grafts fixed with NB-Cn (p = 0.05) compared with those fixed with screws, in both experimental times (analysis of variance). The immunohistochemical evaluation showed that the TRAP expression in a 6-week period was significantly higher compared with the 1-week period, without showing significant difference between the groups (Wilcoxon and MannWhitney). Histological analysis revealed that the NB-Cn caused periosteum damage, but provided bone graft stabilization and incorporation similar to the control group. Conclusion: The perforation provided by screw insertion into the graft during fixation may have triggered early revascularization and remodeling to render increased volume loss compared with the experimental group. These results indicate that the NB-Cn possesses equivalent properties to titanium screw to be used as bone fixation material in osteosynthesis.

Immunoglobulin G profile in hyperacute rejection after multivisceral xenotransplantation

Galvao FHF, Soler W, Pompeu E, Waisberg DR, Mello ES, Costa ACL, Teodoro W, Velosa AP, Capelozzi VL, Antonangelo L, Catanozi S, Martins A, Malbouisson LMS, Cruz RJ, Figueira ER, Filho JAR, Chaib E, D'Albuquerque LAC. Immunoglobulin G profile in hyperacute rejection after multivisceral xenotransplantation. Xenotransplantation 2012; 19: 298304. (c) 2012 John Wiley & Sons A/S. Abstract: Introduction: Xenotransplantation is a potential solution for the high mortality of patients on the waiting list for multivisceral transplantation; nevertheless, hyperacute rejection (HAR) hampers this practice and motivates innovative research. In this report, we describe a model of multivisceral xenotransplantation in which we observed immunoglobulin G (IgG) involvement in HAR. Methods: We recovered en bloc multivisceral grafts (distal esophagus, stomach, small intestine, colon, liver, pancreas, and kidneys) from rabbits (n = 20) and implanted them in the swine (n = 15) or rabbits (n = 5, control). Three hours after graft reperfusion, we collected samples from all graft organs for histological study and to assess IgG fixation by immunofluorescence. Histopathologic findings were graded according to previously described methods. Results: No histopathological features of rejection were seen in the rabbit allografts. In the swine-to-rabbit grafts, features of HAR were moderate in the liver and severe in esophagus, stomach, intestines, spleen, pancreas, and kidney. Xenograft vessels were the central target of HAR. The main lesions included edema, hemorrhage, thrombosis, myosites, fibrinoid degeneration, and necrosis. IgG deposition was intense on cell membranes, mainly in the vascular endothelium. Conclusions: Rabbit-to-swine multivisceral xenotransplants undergo moderate HAR in the liver and severe HAR in the other organs. Moderate HAR in the liver suggests a degree of resistance to the humoral immune response in this organ. Strong IgG fixation in cell membranes, including vascular endothelium, confirms HAR characterized by a primary humoral immune response. This model allows appraisal of HAR in multiple organs and investigation of the livers relative resistance to this immune response.

Platelet-derived exosomes induce endothelial cell apoptosis through peroxynitrite generation: experimental evidence for a novel mechanism of septic vascular dysfunction

Abstract Introduction Several studies link hematological dysfunction to severity of sepsis. Previously we showed that platelet-derived microparticles from septic patients induce vascular cell apoptosis through the NADPH oxidase-dependent release of superoxide. We sought to further characterize the microparticle-dependent vascular injury pathway. Methods During septic shock there is increased generation of thrombin, TNF-α and nitric oxide (NO). Human platelets were exposed for 1 hour to the NO donor diethylamine-NONOate (0.5 μM), lipopolysaccharide (LPS; 100 ng/ml), TNF-α (40 ng/ml), or thrombin (5 IU/ml). Microparticles were recovered through filtration and ultracentrifugation and analyzed by electron microscopy, flow cytometry or Western blotting for protein identification. Redox activity was characterized by lucigenin (5 μM) or coelenterazine (5 μM) luminescence and by 4,5-diaminofluorescein (10 mM) and 2',7'-dichlorofluorescein (10 mM) fluorescence. Endothelial cell apoptosis was detected by phosphatidylserine exposure and by measurement of caspase-3 activity with an enzyme-linked immunoassay. Results Size, morphology, high exposure of the tetraspanins CD9, CD63, and CD81, together with low phosphatidylserine, showed that platelets exposed to NONOate and LPS, but not to TNF-α or thrombin, generate microparticles similar to those recovered from septic patients, and characterize them as exosomes. Luminescence and fluorescence studies, and the use of specific inhibitors, revealed concomitant superoxide and NO generation. Western blots showed the presence of NO synthase II (but not isoforms I or III) and of the NADPH oxidase subunits p22phox, protein disulfide isomerase and Nox. Endothelial cells exposed to the exosomes underwent apoptosis and caspase-3 activation, which were inhibited by NO synthase inhibitors or by a superoxide dismutase mimetic and totally blocked by urate (1 mM), suggesting a role for the peroxynitrite radical. None of these redox properties and proapoptotic effects was evident in microparticles recovered from platelets exposed to thrombin or TNF-α. Conclusion We showed that, in sepsis, NO and bacterial elements are responsible for type-specific platelet-derived exosome generation. Those exosomes have an active role in vascular signaling as redox-active particles that can induce endothelial cell caspase-3 activation and apoptosis by generating superoxide, NO and peroxynitrite. Thus, exosomes must be considered for further developments in understanding and treating vascular dysfunction in sepsis.

Vascular leiomyoma in the oral cavity

The aim of this study was to examine a case report of vascular leiomyoma located in the oral mucosa of the oral cavity. Vascular leiomyoma is a benign tumor arising from smooth muscle. One factor that makes vascular leiomyomas in the oral cavity rare is that there is little smooth muscle in the mouth. The most common histological subtype in the oral cavity is the vascular subtype. The greatest difficulty in histological diagnosis of this entity is the similarity in morphology with other malignancies, particularly of neural or fibroblastic lineage. Wide surgical resection is the only treatment reported in the literature with good results. The recurrence rate is very low if complete resection is achieved. The study of rare or unusual lesions is very important for the clinical diagnosis of vascular leiomyoma

PEEP-ZEEP technique: cardiorespiratory repercussions in mechanically ventilated patients submitted to a coronary artery bypass graft surgery

Abstract Background The PEEP-ZEEP technique is previously described as a lung inflation through a positive pressure enhancement at the end of expiration (PEEP), followed by rapid lung deflation with an abrupt reduction in the PEEP to 0 cmH2O (ZEEP), associated to a manual bilateral thoracic compression. Aim To analyze PEEP-ZEEP technique's repercussions on the cardio-respiratory system in immediate postoperative artery graft bypass patients. Methods 15 patients submitted to a coronary artery bypass graft surgery (CABG) were enrolled prospectively, before, 10 minutes and 30 minutes after the technique. Patients were curarized, intubated, and mechanically ventilated. To perform PEEP-ZEEP technique, saline solution was instilled into their orotracheal tube than the patient was reconnected to the ventilator. Afterwards, the PEEP was increased to 15 cmH2O throughout 5 ventilatory cycles and than the PEEP was rapidly reduced to 0 cmH2O along with manual bilateral thoracic compression. At the end of the procedure, tracheal suction was accomplished. Results The inspiratory peak and plateau pressures increased during the procedure (p < 0.001) compared with other pressures during the assessment periods; however, they were within lung safe limits. The expiratory flow before the procedure were 33 ± 7.87 L/min, increasing significantly during the procedure to 60 ± 6.54 L/min (p < 0.001), diminishing to 35 ± 8.17 L/min at 10 minutes and to 36 ± 8.48 L/min at 30 minutes. Hemodynamic and oxygenation variables were not altered. Conclusion The PEEP-ZEEP technique seems to be safe, without alterations on hemodynamic variables, produces elevated expiratory flow and seems to be an alternative technique for the removal of bronchial secretions in patients submitted to a CABG.

Viabilidade celular da fração mononuclear da medula óssea e fração vascular estromal do tecido adiposo de equinos após o processo de congelamento e descongelamento

Cinco cavalos adultos foram submetidos à coleta de medula óssea do esterno e de tecido adiposo da região glútea. As amostras foram processadas para obtenção da fração mononuclear da medula óssea e fração vascular estromal do tecido adiposo, o número de células obtidas e a viabilidade celular foram determinados. Em seguida, realizou-se o congelamento das amostras em solução contendo 20% de soro fetal bovino e 10% de dimetilsulfóxido. Depois de um mês, realizou-se o descongelamento das amostras e a viabilidade celular foi novamente mensurada. Os resultados revelaram que as técnicas utilizadas tanto para coleta de medula óssea quanto de tecido adiposo em equinos são simples, rápidas e seguras. As metodologias adotadas para o processamento das amostras foram eficientes, obtendo-se aproximadamente 95% de viabilidade celular. Após o descongelamento, a viabilidade média das amostras de células mononucleares da medula óssea foi de 86% e da fração vascular estromal do tecido adiposo de 64%. Frente à importância da terapia celular na clínica médica de equinos, concluiu-se que é necessária a realização de mais estudos, visando padronizar uma técnica de criopreservação que mantenha a integridade das células da fração mononuclear da medula óssea e da fração vascular estromal do tecido adiposo de equinos.

Trombose de veia porta no transplante hepático

INTRODUÇÃO: A trombose de veia porta foi considerada contraindicação ao transplante de fígado no passado em razão da elevada morbi-mortalidade. Diversos avanços permitiram melhora dos resultados. OBJETIVO: Revisão dos avanços e das estratégias cirúrgicas utilizadas para realização do transplante de fígado na vigência de trombose de veia porta. MÉTODO: Revisão da literatura nas bases de dados Medline, Scielo, Lilacs cruzando os descritores: portal vein thrombosis, liver transplantation, vascular complications, jump graft, graft failure, multivisceral transplant. Foram estudados a epidemiologia, fatores de risco, classificação, diagnóstico, estratégias cirúrgicas e resultados. CONCLUSÃO: A trombose de veia porta deixou de ser contraindicação para o transplante hepático. O cirurgião dispõe atualmente de uma série de estratégias para realização do transplante, variando conforme o grau da trombose. Apesar de implicar em maior morbidade e taxas de re-trombose, os resultados do transplante na presença de trombose portal são semelhantes aos observados nas séries habituais.

Fatores de risco para trauma vascular durante a quimioterapia antineoplásica: contribuições do emprego do risco relativo

OBJETIVO: identificar a relação entre os fatores de risco para trauma vascular e o surgimento de eventos adversos de infiltração ou flebite por quimioterapia antineoplásica. MÉTODOS: Estudo de abordagem quantitativa observacional com 30 mulheres com câncer de mama. RESULTADOS: O tipo de material do cateter apresentou associação que sugere risco (RR=2,76; IC=1,199; 6,369); o fator velocidade de infusão apresentou RR=2,22; entretanto, IC= 0,7672; 6,436; os fatores trajetória, número de punção e mobilidade da veia apresentaram RR<1 mas não podem ser considerados como fatores de proteção. Local de inserção e a visibilidade da veia apresentaram risco próximo a 1. CONCLUSÃO: O uso de cateter com metal para punção venosa foi considerado neste estudo como fator para Risco de Trauma Vascular. A análise da associação pelo RR mostrou-se concordante com os dados da literatura pesquisada.

Dental pulp vascular permeability changes induced by dental bleaching

Aiming to compare the effect of different light sources for dental bleaching on vascular permeability of dental pulps, forty-eight incisors were used. The bleaching agent (35 % hydrogen peroxide) was activated by halogen light; LED (Light Emitting Diode) or LED, followed by laser phototherapy (LPT) (λ = 780 nm; 3 J/cm²). After the bleaching procedures, the animals received an intra-arterial dye injection and one hour later were sacrificed. The teeth were diaphanized and photographed. The amount of blue stain content of each dental pulp was quantified using a computer imaging program. The data was statistically compared (p < 0.05). The results showed a significant higher (p < 0.01) dye content in the groups bleached with halogen light, compared with the control, LED and LED plus LPT groups. Thus, tooth bleaching activated by LED or LED plus LPT induces lesser resulted in increased vascular permeability than halogen light.

Análise da rejeição do transplante de aponeurose em coelhos

OBJETIVO: Estudar a viabilidade de aponeurose heteróloga para fechar parede abdominal de coelhos, com ênfase no processo de rejeição. MÉTODOS: Este projeto foi aprovado pelo Comitê de Cuidados Animais da Faculdade de Ciências Médicas da Santa Casa de São Paulo e realizado na Unidade Técnica e Cirurgia Experimental. Quatro coelhas vermelhas trocaram aponeurose da parede abdominal com outros quatro animais machos brancos. Em dois coelhos, foi retirada e substituída a aponeurose como controle do processo cicatricial. Eles foram avaliados 1 vez por dia e sacrificados após 7 dias. Foi realizada a imunoistoquímica com CD20 e CD79. RESULTADOS: Os animais não tiveram celulite, abscesso, hematoma, deiscência da ferida ou hérnia. O local do enxerto mostrou hiperemia intensa. A análise histológica mostrou um processo inflamatório, com a presença de miofibroblastos em amadurecimento e colágeno, que variou de incipiente a moderado. O número de vasos estava reduzido e as células inflamatórias foram, em sua maioria, células plasmáticas e macrófagos. Não havia sinais morfológicos da rejeição aguda com a agressão do endotélio vascular. O músculo adjacente mostrou sinais de degeneração, com reação inflamatória dos núcleos e condensação do citoplasma. A análise imunoistoquímica (CD20 e CD79) mostrou que o processo inflamatório não foi mediado por linfócitos. O teste não paramétrico de Mann-Whitney mostrou que não se pode rejeitar a hipótese de igualdade (p>0,05). CONCLUSÃO: Não houve complicações pós-operatórias (fístulas, deiscência etc.) e a análise histológica revelou processo inflamatório inespecífico. A análise imunoistoquímica mostrou que o processo inflamatório não foi em razão de uma possível rejeição.

Elaboração de um manual ilustrado de exercícios domiciliares para pacientes com hemiparesia secundária ao acidente vascular encefálico (AVE)

A realização de exercícios físicos para pacientes com sequelas motoras pós-acidente vascular encefálico (AVE) é essencial para a recuperação funcional. Programas educacionais podem facilitar a repetição dos exercícios em casa e contribuir para o tratamento. Este trabalho teve como objetivo elaborar e aplicar um manual de exercícios domiciliares para pacientes com AVE. O estudo consistiu em duas etapas: na primeira foi elaborado um manual de exercícios domiciliares (piloto) com fotos e textos simples para facilitar a compreensão. Foi realizada uma avaliação funcional de cada paciente e selecionados os exercícios mais adequados, que deveriam ser feitos em casa. Esse manual foi aplicado a 17 pacientes, 70% crônicos e 30% agudos. Após 15 dias, o paciente retornava e era solicitado que reproduzisse os exercícios e informasse o nível de compreensão das fotos e do texto do manual e se sentia dor ao realizá-los. As fotos e os exercícios referidos como difíceis foram revistos, e criada a versão teste que foi aplicada em outros 23 pacientes, dando origem à versão final do manual. A avaliação do manual piloto foi insatisfatória, sendo que apenas 56% referiram aprovação das fotos e 87% do texto. Após a reformulação, a compreensão das fotos e do texto alcançou valores acima de 98%. Foi possível obter um manual ilustrado de exercícios domiciliares, de fácil aplicação e compreensão, específico e individualizado, para pacientes com AVE e adaptável aos diferentes quadros motores.