Abnormal obturator artery with ipsilateral inferior epigastric artery passed behind the femoral vein / Arteria obturatriz anómala con arteria epigástrica inferior ipsilateral que cruza posterior a la vena femoral

SUMMARY: Clear awareness of the vascular variations is critical in surgeries, which may cause massive hemorrhage during surgical procedures. During educational dissection of a male cadaver, we encountered a combined variation of the left obturator artery and ipsilateral aberrant inferior epigastric artery. The left obturator artery originated from the external iliac artery, then coursed inward, adherent to the superior pubic ramus. The left inferior epigastric artery originated from the femoral artery, and coursed behind the femoral vein. These anatomical variations shown in one person were extremely rare. This is particularly true with regard to these variations while performing pelvic and inguinal region surgeries.

El conocimiento claro de las variaciones vasculares es fundamental en las cirugías, ya que pueden causar una hemorragia masiva durante los procedimientos quirúrgicos. Durante la disección educativa de un cadáver de sexo masculino, encontramos una variación combinada de la arteria obturatriz izquierda y la arteria epigástrica inferior ipsilateral aberrante. La arteria obturatriz izquierda se originaba en la arteria ilíaca externa, luego discurrió hacia medial, adhiriéndose a la rama púbica superior. La arteria epigástrica inferior izquierda se originaba en la arteria femoral y discurría por detrás de la vena femoral. Estas variaciones anatómicas mostradas en una sola persona son extremadamente raras. Esto es importante de conocer estas variaciones cuando se realizan cirugías de las regiones pélvica e inguinal.

Docosahexaenoic fatty acid nanoencapsulated with Anti-PECAM-1 as strategy to increase atherosclerotic plaque stability / Ácido graxo docosahexaenoico nanoencapsulado com anti-PECAM-1 como uma estratégia para aumentar a estabilidade de placas ateroscleróticas

Cardiovascular diseases (CVDs) are the main cause of mortality worldwide, being the ischemic heart disease responsible for 85% of deaths. Atherosclerosis is a chronic inflammation of the arteries that underlies ischemic forms of CVD and involves the innate and adaptive immune systems, from initial fatty streak formation to atherosclerotic plaque ruptures, which defines the beginning and end stages of disease, respectively. Recent research on the reduction of systemic inflammation in order to treat CVD is controversial, since results show that this reduced inflammation can also increase patient susceptibility to general infection. Therefore, new tissue-targeting strategies are necessary. Docosahexaenoic fatty acid (DHA) is a natural bioactive precursor of pro-resolving oxylipins that can reduce inflammation. Based on these factors, the objective of this study was to develop a nanocapsule containing algae oil as a DHA source and apply anti-PECAM-1 on its surface to drive it to the inflamed endothelium. Initially, a surface-functionalized metal-complex multi-wall nanocapsule containing algae oil in its nucleus (MLNC-DHA-a1) was developed. This nanocapsules presented a mean diameter of 163 ± 5 nm, was spherical in shape, showed 94.80% conjugation efficiency using 200 µg/mL of anti-PECAM-1 on the surface, and did not show significant toxicity toward HUVECs at concentrations from 0.14 to 2.90x1011 nanocapsules/mL. The nanocapsules were also stable for 2 h, sufficient time to allow for clinical applications. In cell viability assays, concentrations of 0.14 to 1.40x1011 nanocapsules/mL did not significantly affect the viability of immortalized murine macrophages (RAW 264.7) and U-937 cells after 24, 48, and 72 h of treatment. Finally, macrophages were incubated with 0.75x1011 MLNC-DHA-a1 nanocapsules/mL for 4 h and showed a significant uptake, observed using dark-field hyperspectral microscopy (CytoViva®). Once inside murine macrophages (RAW 264.7), MLNC-DHA-a1 nanocapsules promoted a strong increase in M2 phenotype polarization compared to non-treated control cells. Our results suggest that DHA-enriched algae oil, as part of a lipid core nanocapsules, does not reduce cell viability and improves macrophage phenotype, making it a promising potential therapy for controlling chronic inflammation and healing or stabilizing atherosclerotic plaques

As doenças cardiovasculares (DCVs) são a principal causa de mortalidade no mundo, sendo os eventos isquêmicos responsáveis por 85% das mortes. A aterosclerose é uma inflamação crônica das artérias associada aos eventos isquêmicos das DCVs, na qual o sistema imunológico inato e adaptativo estão envolvidos desde a formação inicial das estrias gordurosas até a ruptura das placas ateroscleróticas. Pesquisas recentes direcionadas à redução da inflamação sistêmica têm mostrado resultados controversos, pois essa abordagem pode aumentar a susceptibilidade do paciente a infecções. Nesse sentido, novas estratégias direcionadas ao tecido lesionado são necessárias. No que se refere a medicamentos anti-inflamatórios ou suplementos alimentares, o ácido docosaexaenóico (DHA) tem sido relatado como um precursor natural de oxilipinas pró- resolutivas. Baseado nesse contexto, o objetivo deste estudo foi desenvolver nanocápsulas contendo óleo de alga como fonte de DHA e vetorizar essas nanopartículas com o anticorpo antiPECAM-1 em sua superfície, visando direcioná-las ao endotélio inflamado. Inicialmente, a nanocápsula multiparede metal-complexa funcionalizada contendo óleo de alga em seu núcleo (MLNC-DHA-a1) foi desenvolvida, apresentando um diâmetro médio de 163 ± 5 nm, formato esférico, onde a eficiência de conjugação do anti-PECAM-1 (200 µg/mL) foi de 94,80% sem toxicidade significativa em HUVECs nas concentrações de 1.14 a 2.9 x 1011 nanocápsulas/mL. As nanocápsulas apresentaram uma estabilidade de 2h, o que representa tempo suficiente para a sua aplicação clínica. A seguir, ensaios de viabilidade celular foram realizados em outras linhagens de células para avaliar a toxicidade das nanocápsulas. As concentrações de 0.14 a 1.40 x 1011 de nanocápsulas/mL não afetaram significativamente a viabilidade celular de macrófagos murinos imortalizados (RAW 264.7) e U-937 após 24, 48 e 72 h de tratamento. Por fim, os macrófagos (RAW 264.7) foram incubados com 0.75 x 1011 MLNC-DHA-a1/mL durante 4 h e apresentam uma captação significativa das nanocápsulas, observada por microscopia hiperespectral de campo escuro (CytoViva®). Uma vez captadas pelos macrófagos murinos imortalizados (RAW 264.7), as nanoformulações MLNC-DHA-a1 promoveram um forte aumento da polarização do fenótipo M2 em comparação com as células controle não tratadas. Nossos resultados sugerem que o óleo de alga rico em DHA presente no núcleo lipídico das nanocápsulas, não reduziu a viabilidade celular e estimulou uma maior polarização de macrófagos para o tipo M2, sendo assim uma terapia potencial para controlar a inflamação crônica e cicatrizar ou estabilizar placas ateroscleróticas

Imunização de camundongos LDLr-/- com peptídeo mimético da LDL eletronegativa: uma potencial estratégia terapêutica para a aterosclerose / Immunization of LDLr - / - mice with electronegative LDL mimetic peptides: a potential therapeutic strategy for atherosclerosis

Introdução: A aterosclerose é uma doença inflamatória crônica decorrente de alterações na parede das artérias de médio e grande calibre e associadas a diversos fatores de risco, dentre os quais destaca-se as hiperlipidemias, ou seja, o aumento plasmático das lipoproteínas, mas também outras comorbidades, como a Síndrome Metabólica. Entre as lipoproteínas, a lipoproteína de baixa densidade (LDL) é de grande relevância na aterosclerose. Diferentes espécies de LDL modificada (LDLm) são originadas através de lipólise, glicação e proteólise, além da oxidação, variando em densidade e eletronegatividade, sendo melhor denominada LDL eletronegativa [LDL (-)]. Considerando as diferenças conformacionais entre a estrutura da ApoB-100 da LDL nativa e da LDL (-), em um estudo inicial, nosso grupo desenvolveu um anticorpo monoclonal (2C7) a partir da imunização de camundongos Balb/c com a LDL (-) humana. Em uma etapa seguinte foi mapeado o epítopo reconhecido pelo anticorpo monoclonal anti-LDL (-) através de phage display. O peptídeo ligante do anticorpo monoclonal anti-LDL (-) foi nomeado p2C7. Esse peptídeo não representa regiões da sequência linear da ApoB-100 humana, mas microdomínios conformacionais de epítopos da ApoB-100 da LDL (-), tornando-os candidatos para a imunomodulação da aterogênese. Portanto, investigar a imunomodulação induzida pelos peptídeo p2C7 miméticos da LDL (-), por representar um epítopo imunodominante da LDL (-), poderá abrir novas perspectivas terapêuticas futuras para a imunomodulação da aterosclerose. Objetivo: Avaliar a imunomodulação promovida pelo p2C7 in vivo, utilizando camundongos C57BL/6 LDLr -/- e amostras de plasma humano. Adicionalmente, no estágio (BEPE) realizado no Instituto Karolinska (dezembro de 2019 a março de 2021), investigou-se o imunometabolismo como mediador nas doenças cardiovasculares. Na parte II-A, estão descritos os resultados do estudo inicialmente proposto. Na parte II-B, apresenta-se os resultados que foram desenvolvidos posteriormente, com ampliação do escopo do projeto, abordando-se a inflamação vascular envolvida no aneurisma de aorta abdominal através de ferramentas de bioinformática. Na parte II-C, são apresentados os resultados do estudo do envolvimento da enzima indolamina 2,3 dioxigenase (IDO) na esteatohepatite não-alcoólica (NASH) e aterosclerose em camundongos ApoE-/- and ApoE/IDO/double-knockout. Metodologia: Foi avaliada a presença de anticorpos anti-p2C7 em amostras de plasma humano de indivíduos com ou sem síndrome metabólica. Realizamos a determinação de TNF circulante nas mesmas amostras e prosseguimos com regressões lineares associando os parâmetros inflamatórios com os níveis de anticorpos anti-p2C7. Camundongos C57BL/6 LDLr -/- foram imunizados com p2C7 e os adjuvantes Alum ou Montanide ISA 720, analisando-se os títulos de anticorpos contra p2C7 e LDL (-), a produção de citocinas (IL-10, IL-4, IL-2, IL-6, IFNγ, IL-17, TNFα) e células secretoras de anticorpos. Camundongos C57BL/6 LDLr -/- foram tolerizados contra os peptídeos mimotopos, com injeções intravenosas (veia caudal) e desafiados com a imunização contendo LDL (-) + Alum. Avaliou-se os títulos de anticorpos contra p2C7 e LDL (-) e a produção de citocinas (TNF-α, IFNγ, IL-12, IL-6, IL-10 e MCP-1). Os camundongos foram mantidos em dieta hipercolesterolêmica por 3 meses para formação da placa aterosclerótica. Após este período, os camundongos foram eutanasiados, avaliando-se a formação de placa aterosclerótica na artéria abdominal e arco aórtico, assim como a produção de citocinas (TNF-α, IFNγ, IL-12, IL-6, IL-10 e MCP-1). Camundongos C57BL/6 LDLr -/- foram imunizados com OVA-p2C7 e, após dieta hipercolesterolêmica de 3 meses para formação de placa aterosclerótica, foram avaliados os parâmetros inflamatórios e avaliada a captação de 18F-FDG no arco aórtico através de PET/CT. Resultados: A imunização com o p2C7 (livre) não foi capaz de induzir resposta humoral, não se observando títulos detectáveis de anticorpos reativos à p2C7 ou LDL (-) em nenhum camundongo imunizado, assim como não foram detectadas células secretoras de anticorpos específicos para a LDL (-). O grupo imunizado com Alum ou Montanide + p2C7 teve aumento significativo na produção de TNF- quando comparado com os demais grupos. O protocolo de tolerização foi realizado com sucesso, visto que os camundongos tolerizados apresentaram títulos de anticorpos inferiores aos controles para o epítopo utilizado. Apenas os camundongos tolerizados com o p2C7 apresentaram aumento significativo na produção de IL-6, IL-12, IL-10, TNF-α, IFNγ e MCP 1 após dieta hipercolesterolêmica. A imunização ativa com OVA-p2C7 foi capaz de reduzir a produção de TNF induzida pela dieta hipercolesterolêmica, assim como reduzir a captação de 18F-FDG. Conclusão: o epítopo p2C7 é altamente expresso na LDL (-) de pacientes com maior risco cardiovascular. Além disso, a imunização ativa com p2C7 também se mostra uma ferramenta promissora para prevenir e regular a inflamação causada pela LDL (-) no curso da aterosclerose

Introduction: Atherosclerosis is a chronic inflammatory disease resulting from changes in the wall of medium and large-caliber arteries and associated with several risk factors, among which hyperlipidemias stand out, ie, the increase in plasma lipoproteins, but also other comorbidities, such as Metabolic Syndrome. Among the lipoproteins, low-density lipoprotein (LDL) is of great relevance in atherosclerosis. Different isoforms of modified LDL (LDLm) are originated through lipolysis, glycation and proteolysis, in addition to oxidation, varying in density and electronegativity, being better called electronegative LDL [LDL (-)]. Considering the conformational differences between the ApoB-100 structure of native LDL and LDL (-), in an initial study, our group developed a monoclonal antibody (2C7) from the immunization of Balb/c mice with human LDL (-). In a next step, the epitope recognized by the anti-LDL monoclonal antibody (-) was mapped using phage display. The binding peptide of anti-LDL monoclonal antibodies (-) was named p2C7. This peptide does not represent linear sequence regions of human ApoB-100, but conformational microdomains of LDL (-) ApoB-100 epitopes, making them candidates for the immunomodulation of atherogenesis. Therefore, investigating the immunomodulation induced by p2C7 peptide mimetics of LDL (-) as it represents an immunodominant epitope of LDL (-) could open new future therapeutic perspectives for the immunomodulation of atherosclerosis. Objective: To evaluate the immunomodulation promoted by p2C7 in vivo, using C57BL/6 LDLr -/- mice, and human plasma samples. In addition, in the internship (BEPE), held at the Karolinska Institute (December 2019 to March 2021), immunometabolism as a mediator of Cardiovascular Diseases was studied. In part II-A, the results of the initially proposed study are described. In part II-B, the results that were developed later are presented, expanding the scope of the project, approaching the vascular inflammation involved in the abdominal aortic aneurysm through bioinformatics tools. In part II-C, the results of the study of the involvement of the enzyme indoleamine 2,3 dioxygenase (IDO) in non-alcoholic steatohepatitis (NASH) and atherosclerosis in ApoE-/- and ApoE/IDO/double mice are presented -knockout. Methodology: The presence of anti-p2C7 antibodies in human plasma samples with or without Metabolic Syndrome was evaluated. We measured circulating TNF in the same samples and proceeded with linear regressions associating inflammatory parameters with levels of anti-p2C7 antibodies. C57BL/6 LDLr -/- mice were immunized with p2C7 and the adjuvants Alum or Montanide ISA 720, analyzing the antibody titers against p2C7 and LDL (-), the production of cytokines (IL-10, IL-4, IL -2, IL-6, IFNγ, IL-17, TNFα) and antibody-secreting cells. C57BL/6 LDLr -/- mice were tolerized against mimotope peptides with intravenous injections (caudal vein) and challenged with immunization containing LDL (-) + Alum. Antibody titers against p2C7 and LDL (-) and cytokine production (TNF-α, IFNγ, IL-12, IL-6, IL-10 and MCP-1) were evaluated. The mice were kept on a hypercholesterolemic diet for 3 months for atherosclerotic plaque formation. After this period, the mice were euthanized, evaluating the formation of atherosclerotic plaque in the abdominal artery and aortic arch, as well as the production of cytokines (TNF-α, IFNγ, IL-12, IL-6, IL-10 and MCP -1). C57BL/6 LDLr -/- mice were immunized with OVA-p2C7 and, after a 3-month hypercholesterolemic diet for atherosclerotic plaque formation, inflammatory parameters were evaluated and 18F-FDG uptake was evaluated by PET/CT. Results: Immunization with p2C7 (free) was not able to induce a humoral response, with no detectable titers of antibodies reactive to p2C7 or LDL (-) being observed in any immunized mouse, as well as no detectable antibody-secreting cells for the LDL (-). The group immunized with Alum or Montanide + p2C7 had a significant increase in TNF-α production when compared to the other groups. The tolerance protocol was successfully performed, as the tolerized mice had lower antibody titers than controls for the epitope used. Only mice tolerated with p2C7 showed a significant increase in the production of IL-6, IL-12, IL-10, TNF-α, IFNγ and MCP 1 after a hypercholesterolemic diet. Active immunization with OVA-p2C7 was able to reduce TNF production induced by the hypercholesterolemic diet, as well as to reduce 18F-FDG uptake. Conclusion: the p2C7 epitope is highly expressed in LDL (-) of patients with higher cardiovascular risk. Furthermore, active immunization with p2C7 is also a promising tool to prevent and regulate inflammation caused by LDL (-) in the course of atherosclerosis

Imunização de camundongos LDLr-/- com peptídeo mimético da LDL eletronegativa: uma potencial estratégia terapêutica para a ateroscleros / Immunization of LDLr - / - mice with electronegative LDL mimetic peptides: a potential therapeutic strategy for atherosclerosis

Introdução: A aterosclerose é uma doença inflamatória crônica decorrente de alterações na parede das artérias de médio e grande calibre e associadas a diversos fatores de risco, dentre os quais destaca-se as hiperlipidemias, ou seja, o aumento plasmático das lipoproteínas, mas também outras comorbidades, como a Síndrome Metabólica. Entre as lipoproteínas, a lipoproteína de baixa densidade (LDL) é de grande relevância na aterosclerose. Diferentes espécies de LDL modificada (LDLm) são originadas através de lipólise, glicação e proteólise, além da oxidação, variando em densidade e eletronegatividade, sendo melhor denominada LDL eletronegativa [LDL (-)]. Considerando as diferenças conformacionais entre a estrutura da ApoB-100 da LDL nativa e da LDL (-), em um estudo inicial, nosso grupo desenvolveu um anticorpo monoclonal (2C7) a partir da imunização de camundongos Balb/c com a LDL (-) humana. Em uma etapa seguinte foi mapeado o epítopo reconhecido pelo anticorpo monoclonal anti-LDL (-) através de phage display. O peptídeo ligante do anticorpo monoclonal anti-LDL (-) foi nomeado p2C7. Esse peptídeo não representa regiões da sequência linear da ApoB-100 humana, mas microdomínios conformacionais de epítopos da ApoB-100 da LDL (-), tornando-os candidatos para a imunomodulação da aterogênese. Portanto, investigar a imunomodulação induzida pelos peptídeo p2C7 miméticos da LDL (-), por representar um epítopo imunodominante da LDL (-), poderá abrir novas perspectivas terapêuticas futuras para a imunomodulação da aterosclerose. Objetivo: Avaliar a imunomodulação promovida pelo p2C7 in vivo, utilizando camundongos C57BL/6 LDLr -/- e amostras de plasma humano. Adicionalmente, no estágio (BEPE) realizado no Instituto Karolinska (dezembro de 2019 a março de 2021), investigou-se o imunometabolismo como mediador nas doenças cardiovasculares. Na parte II-A, estão descritos os resultados do estudo inicialmente proposto. Na parte II-B, apresenta-se os resultados que foram desenvolvidos posteriormente, com ampliação do escopo do projeto, abordando-se a inflamação vascular envolvida no aneurisma de aorta abdominal através de ferramentas de bioinformática. Na parte II-C, são apresentados os resultados do estudo do envolvimento da enzima indolamina 2,3 dioxigenase (IDO) na esteatohepatite não-alcoólica (NASH) e aterosclerose em camundongos ApoE-/- and ApoE/IDO/double-knockout. Metodologia: Foi avaliada a presença de anticorpos anti-p2C7 em amostras de plasma humano de indivíduos com ou sem síndrome metabólica. Realizamos a determinação de TNF circulante nas mesmas amostras e prosseguimos com regressões lineares associando os parâmetros inflamatórios com os níveis de anticorpos anti-p2C7. Camundongos C57BL/6 LDLr -/- foram imunizados com p2C7 e os adjuvantes Alum ou Montanide ISA 720, analisando-se os títulos de anticorpos contra p2C7 e LDL (-), a produção de citocinas (IL-10, IL-4, IL-2, IL-6, IFNγ, IL-17, TNFα) e células secretoras de anticorpos. Camundongos C57BL/6 LDLr -/- foram tolerizados contra os peptídeos mimotopos, com injeções intravenosas (veia caudal) e desafiados com a imunização contendo LDL (-) + Alum. Avaliou-se os títulos de anticorpos contra p2C7 e LDL (-) e a produção de citocinas (TNF-α, IFNγ, IL-12, IL-6, IL-10 e MCP-1). Os camundongos foram mantidos em dieta hipercolesterolêmica por 3 meses para formação da placa aterosclerótica. Após este período, os camundongos foram eutanasiados, avaliando-se a formação de placa aterosclerótica na artéria abdominal e arco aórtico, assim como a produção de citocinas (TNF-α, IFNγ, IL-12, IL-6, IL-10 e MCP-1). Camundongos C57BL/6 LDLr -/- foram imunizados com OVA-p2C7 e, após dieta hipercolesterolêmica de 3 meses para formação de placa aterosclerótica, foram avaliados os parâmetros inflamatórios e avaliada a captação de 18F-FDG no arco aórtico através de PET/CT. Resultados: A imunização com o p2C7 (livre) não foi capaz de induzir resposta humoral, não se observando títulos detectáveis de anticorpos reativos à p2C7 ou LDL (-) em nenhum camundongo imunizado, assim como não foram detectadas células secretoras de anticorpos específicos para a LDL (-). O grupo imunizado com Alum ou Montanide + p2C7 teve aumento significativo na produção de TNF- quando comparado com os demais grupos. O protocolo de tolerização foi realizado com sucesso, visto que os camundongos tolerizados apresentaram títulos de anticorpos inferiores aos controles para o epítopo utilizado. Apenas os camundongos tolerizados com o p2C7 apresentaram aumento significativo na produção de IL-6, IL-12, IL-10, TNF-α, IFNγ e MCP 1 após dieta hipercolesterolêmica. A imunização ativa com OVA-p2C7 foi capaz de reduzir a produção de TNF induzida pela dieta hipercolesterolêmica, assim como reduzir a captação de 18F-FDG. Conclusão: o epítopo p2C7 é altamente expresso na LDL (-) de pacientes com maior risco cardiovascular. Além disso, a imunização ativa com p2C7 também se mostra uma ferramenta promissora para prevenir e regular a inflamação causada pela LDL (-) no curso da aterosclerose

Introduction: Atherosclerosis is a chronic inflammatory disease resulting from changes in the wall of medium and large-caliber arteries and associated with several risk factors, among which hyperlipidemias stand out, ie, the increase in plasma lipoproteins, but also other comorbidities, such as Metabolic Syndrome. Among the lipoproteins, low-density lipoprotein (LDL) is of great relevance in atherosclerosis. Different isoforms of modified LDL (LDLm) are originated through lipolysis, glycation and proteolysis, in addition to oxidation, varying in density and electronegativity, being better called electronegative LDL [LDL (-)]. Considering the conformational differences between the ApoB-100 structure of native LDL and LDL (-), in an initial study, our group developed a monoclonal antibody (2C7) from the immunization of Balb/c mice with human LDL (-). In a next step, the epitope recognized by the anti-LDL monoclonal antibody (-) was mapped using phage display. The binding peptide of anti-LDL monoclonal antibodies (-) was named p2C7. This peptide does not represent linear sequence regions of human ApoB-100, but conformational microdomains of LDL (-) ApoB-100 epitopes, making them candidates for the immunomodulation of atherogenesis. Therefore, investigating the immunomodulation induced by p2C7 peptide mimetics of LDL (-) as it represents an immunodominant epitope of LDL (-) could open new future therapeutic perspectives for the immunomodulation of atherosclerosis. Objective: To evaluate the immunomodulation promoted by p2C7 in vivo, using C57BL/6 LDLr -/- mice, and human plasma samples. In addition, in the internship (BEPE), held at the Karolinska Institute (December 2019 to March 2021), immunometabolism as a mediator of Cardiovascular Diseases was studied. In part II-A, the results of the initially proposed study are described. In part II-B, the results that were developed later are presented, expanding the scope of the project, approaching the vascular inflammation involved in the abdominal aortic aneurysm through bioinformatics tools. In part II-C, the results of the study of the involvement of the enzyme indoleamine 2,3 dioxygenase (IDO) in non-alcoholic steatohepatitis (NASH) and atherosclerosis in ApoE-/- and ApoE/IDO/double mice are presented -knockout. Methodology: The presence of anti-p2C7 antibodies in human plasma samples with or without Metabolic Syndrome was evaluated. We measured circulating TNF in the same samples and proceeded with linear regressions associating inflammatory parameters with levels of anti-p2C7 antibodies. C57BL/6 LDLr -/- mice were immunized with p2C7 and the adjuvants Alum or Montanide ISA 720, analyzing the antibody titers against p2C7 and LDL (-), the production of cytokines (IL-10, IL-4, IL -2, IL-6, IFNγ, IL-17, TNFα) and antibody-secreting cells. C57BL/6 LDLr -/- mice were tolerized against mimotope peptides with intravenous injections (caudal vein) and challenged with immunization containing LDL (-) + Alum. Antibody titers against p2C7 and LDL (-) and cytokine production (TNF-α, IFNγ, IL-12, IL-6, IL-10 and MCP-1) were evaluated. The mice were kept on a hypercholesterolemic diet for 3 months for atherosclerotic plaque formation. After this period, the mice were euthanized, evaluating the formation of atherosclerotic plaque in the abdominal artery and aortic arch, as well as the production of cytokines (TNF-α, IFNγ, IL-12, IL-6, IL-10 and MCP -1). C57BL/6 LDLr -/- mice were immunized with OVA-p2C7 and, after a 3-month hypercholesterolemic diet for atherosclerotic plaque formation, inflammatory parameters were evaluated and 18F-FDG uptake was evaluated by PET/CT. Results: Immunization with p2C7 (free) was not able to induce a humoral response, with no detectable titers of antibodies reactive to p2C7 or LDL (-) being observed in any immunized mouse, as well as no detectable antibody-secreting cells for the LDL (-). The group immunized with Alum or Montanide + p2C7 had a significant increase in TNF-α production when compared to the other groups. The tolerance protocol was successfully performed, as the tolerized mice had lower antibody titers than controls for the epitope used. Only mice tolerated with p2C7 showed a significant increase in the production of IL-6, IL-12, IL-10, TNF-α, IFNγ and MCP 1 after a hypercholesterolemic diet. Active immunization with OVA-p2C7 was able to reduce TNF production induced by the hypercholesterolemic diet, as well as to reduce 18F-FDG uptake. Conclusion: the p2C7 epitope is highly expressed in LDL (-) of patients with higher cardiovascular risk. Furthermore, active immunization with p2C7 is also a promising tool to prevent and regulate inflammation caused by LDL (-) in the course of atherosclerosis

Angiotomografía de las variantes anatómicas de la arteria cística: estudio en el preoperatorio de colelitiasis / Angiotomography of the anatomical variants of the cystic artery: pre-operative study of cholelithiasis

La colecistectomía laparoscópica es el tratamiento indicado en la colelitiasis, sin embargo el procedimiento no está exento de complicaciones o morbilidad concomitante. Es posible que, debido a lesiones ductales colaterales, ocurra sangrado con posibilidad de conversión de la cirugía e indeseables resultados. Para un correcto abordaje de la región se hace fundamental la identificación del trígono cistohepático (TCH) y sus componentes, a su vez de la ligadura y sección de la arteria cística (AC). Conociendo la elevada variabilidad de la AC, el objetivo de este trabajo consistió en identificar el número, origen, trayecto y relación de la AC con el TCH y sus variaciones, utilizando angiotomografía por medio de un tomógrafo detector de 64 cortes, en el preoperatorio de 30 pacientes de sexo femenino, entre 24 y 54 años de edad, con colelitiasis diagnosticadas clínicamente y por ecosonografía. La AC en el 76,67 % era única y se encontraba dentro del TCH, en el 16,67 % era única y se observó fuera del TCH. En el 6,67 % se observaron dos AC, una dentro y otra fuera del TCH. En el 66,67 % de los casos la AC se originaba de manera normal de la arteria hepática derecha. La trazabilidad de la AC fue en el 53,3 % medianamente visible y en el 46,7 % de trazabilidad excelente. En conclusión, la identificación de la AC y sus variaciones anatómicas se puede determinar en el preoperatorio y puede ser útil para mejorar el plan quirúrgico en pacientes con colelitiasis, brindando información al procedimiento, optimizarlo y disminuir los riesgos de eventuales complicaciones relacionados con sangrado.

Laparoscopic cholecystectomy is the treatment indicated for cholelithiasis, however the procedure is not free of complications or concomitant morbidity. It is possible that, due to collateral ductal lesions, bleeding occurs with the possibility of surgery conversion and undesirable results. For a correct approach to the region it is essential to identify the cystohepatic trigone (CHT) and its components, as well as the ligation and section of the cystic artery (AC). Knowing the high variability of CA, the aim of this work was to identify the number, origin, path and relationship of CA with the CHT and its variations using angiotomography by means of a 64-slice detector tomograph in the preoperative period of 30 female patients, between 24 and 54 years old, with clinically diagnosed cholelithiasis and by echo sonography. The AC in 76.67 % was unique and was within the CHT, in 16.67 % it was unique and was observed outside the CHT. In 6.67 %, two ACs were observed, one inside and one outside the TCH. In 66.67 % of cases, CA originated normally from the right hepatic artery. The traceability of AC was 53.3 % moderately visible and 46.7 % excellent traceability. In conclusion, the identification of AC and its anatomical variations can be determined in the preoperative period and can be useful to improve the surgical plan in patients with cholelithiasis, providing information on the procedure, optimizing it and reducing the risks of possible bleeding related complications.

A rare variation of suprascapular artery originated from the axillary artery / Una rara variación de la arteria supraescapular originada de la arteria axilar

SUMMARY: The suprascapular artery (SSA) has been identified to be of clinical relevance to clavicular fracture, suprascapular neuropathy and surgical intervention of shoulder. Thus its origin and course have been intensively studied. In this case, we found a unilateral variation of the suprascapular artery, originating from the 1st segment of axillary artery, and sequentially penetrating the upper trunk of brachial plexus, passing through the suprascapular notch under the superior transverse scapular ligament. This case will be helpful to clinical management in cervical and shoulder region.

RESUMEN: Se ha identificado que la arteria supraescapular (ASS) tiene relevancia clínica en la fractura clavicular, la neuropatía supraescapular y la intervención quirúrgica del hombro. En consecuencia, su origen y su curso han sido ampliamente estudiados. En este caso, encontramos una variación unilateral de la arteria supraescapular, originada en el primer segmento de la arteria axilar, y que penetraba secuencialmente en el tronco superior del plexo braquial, pasando a través de la incisura supraescapular debajo del ligamento escapular transverso superior. Este caso será útil para el manejo clínico en la región cervical y del hombro.

Clip Ovesco® como tratamiento de rescate en lesión de Dieulafoy duodenal con sangrado activo / Ovesco clip as a rescue treatment of duodenal Dieulafoy lesion with active bleeding

Las lesiones de Dieulafoy se definen como una anomalía vascular que producen un sangrado en la mucosa proveniente de una arteria submucosa anormalmente larga y tortuosa que se ubican principalmente en estómago (80%), con poca frecuencia a nivel duodenal y constituyen el 6% de los sangrados gastrointestinales no asociados a varices y del 1% al 2% de todos los sangrados gastrointestinales. Reportamos el caso de un paciente masculino de 60 años que ingresó por hematemesis, melena y signos de hipovolemia con hemoglobina de 9 g/dl, que luego de realizar su compensación hemodinámica se le realizó una endoscopía alta que evidenció una lesión de Dieulafoy con sangrado activo severo en la segunda porción duodenal realizándosele inyección con adrenalina al 1:10 000 sobre los bordes de la lesión, pero al no lograrse una hemostasia adecuada se le tuvo que realizar la colocación de un clip ovesco con hemostasia efectiva que se corroboró 24 horas después, a través de una segunda endoscopía para poder egresar al paciente sin complicaciones, ni resangrado.

Dieulafoy's lesions are vascular anomalies that produce gastrointestinal bleeding of the mucosa from an abnormally long and tortuous submucosal artery. It is found predominately in the stomach (80%) and less frequently in the duodenum. They constitute the 6% of all non-variceal bleeding and the 1 to 2% of all gastrointestinal bleeding source. We report a case of a 60-year-old man with hematemesis, melena and signs of hypovolemic shock with a hemoglobin level of 9 g/dL. After adequate fluid resuscitation, an upper endoscopy showed an actively bleeding Dieulafoy lesion in the second portion of the duodenum. After epinephrine injection over lesion borders, an adequate hemostasis was not achieved. An over-the-scope clip was placed. Follow-up endoscopy 24 hours later showed an effective hemostasis and the patient was discharged without complications or re-bleeding.

Sonographic Findings of the Bifid Median Nerve and Persistent Median Artery in Carpal Tunnel: A Preliminary Study in Chinese Individuals

OBJECTIVE: The aim of this study was to investigate the prevalence of anatomic variations of the bifid median nerve, persistent median artery and persistent median vein in Chinese individuals and their relationship with carpal tunnel syndrome. METHODS: One hundred and sixty median nerves were examined using ultrasonography and colour Doppler ultrasonography. The location, shape, and size of the bifid median nerve, persistent median artery and persistent median vein were recorded. The cross-sectional area of the bifid median nerve (two trunks) was measured at the level of the pisiform. RESULTS: Among the 160 wrists examined, a bifid median nerve was observed in 15 (9.4%) wrists, and a persistent median artery was observed in 12 (7.5%) wrists. These two variations either coexisted or were observed independently, and the probability of coexistence (6.3%) was higher than the probability of existing independently (bifid median nerve only 3.1%, persistent median artery only 1.3%). The cross-sectional area of the radial trunk was greater than (13 in 15, 86.7%) the cross-sectional area of the ulnaris trunk. Persistent median vein was observed in 9 wrists (5.6%). CONCLUSIONS: The persistent median artery and bifid median nerve tend to coexist, and the persistent median vein sometimes runs parallel to the persistent median artery. Their positional relationship in carpal tunnel is uncertain, and thus, preoperative ultrasound is necessary. These three variations do not present any additional risk for the development of carpal tunnel syndrome.

Coupled multiple musculo-neurovascular variations in same upper limb: a case report and clinical significances / Múltiples variaciones músculo-neurovasculares conectados en el mismo miembro superior: reporte de un caso y significados clínicos

Variants of the median nerve, extra forearm flexor muscles heads are relationships of the persistent median artery (PMA) that have been extensively reported. We report the findings of a PMA (diam. 3.25 mm), a pierced median nerve, and accessory heads of the flexor digitorum profundus (FDP) and flexor policis longus (FPL) muscles coexisting with a brachioradial artery (BRA) (diam.1.8mm) in the left upper limb of a 65 year-old male cadaver. The median nerve provided a ring for the passage of the PMA about the junction of the proximal and middle thirds of the forearm. Both accessory muscles were placed anterior to the ulnar artery, with the brachioradial artery coursing superficially in the brachium and antebrachium. The notable diameter of the PMA may be etiological in the causation of a carpal tunnel syndrome, while the hypoplastic BRA may pose some challenges inits selection as good conduit for catheterization and other surgical interventions like CABG in the upper limb. Additional clinical interest include the possible reduction in blood supply to the hand from the compressive effect of the 2 accessory muscles on the ulnar artery and possible inadvertent drug injection due to the superficial placement of the brachioradial artery close to veins.

Variantes del nervio mediano y cabezas adicionales de los músculos flexores del antebrazo, se relacionan con la arteria mediana persistente (AMP). Presentamos los resultados de una AMP (diámetro 3,25 mm), un nervio mediano pinzado y cabezas accesorias de los músculos flexor profundo de los dedos (FPD) y flexor largo del pulgar (FLP) que coexisten con una arteria braquiorradial (ABR) (diámetro 1,8 mm) en el miembro superior izquierdo de un cadáver de sexo masculino de 65 años. El nervio mediano proporciona un anillo para el paso de la AMP sobre la unión de los tercios proximal y medio del antebrazo. Ambos músculos accesorios se colocaron por delante de la arteria ulnar, con la arteria braquiorradial ubicada superficialmente en el brazo y en el antebrazo. El diámetro notable de la AMP puede ser la causa del síndrome del túnel carpiano, mientras que la ABR hipoplásica puede plantear algunos desafíos en su selección como buen conducto para la cateterización y otras intervenciones quirúrgicas como la cirugía de revascularización coronaria a partir del miembro superior. De interés clínico se considera la posible reducción en el suministro de sangre debido a la compresión de los 2 músculos accesorios a la arteria ulnar y la posible inyección fallida de drogas debido a la ubicación superficial de la arteria braquiorradial, cercana a las venas.

Neuro-Vascular Variation in Axilla.

A variation in the branching pattern of third part of axillary artery was observed in the right upper limb of an adult male cadaver during routine dissection. The axillary artery gave a large abnormal arterial trunk. This trunk branched into anterior circumflex humeral, subscapular and profunda brachii artery. Subscapular trunk further divided into posterior circumflex humeral and circumflex scapular artery. There was abnormal formation of median nerve by two roots, anterior to abnormal arterial trunk. Medial root of median nerve was present behind axillary artery. Ulnar nerve was also formed around the abnormal trunk by medial and lateral roots. This abnormality might cause neurovascular compression in the upper limb like compression of abnormal arterial trunk by two roots of median nerve and compression of medial root of median nerve by axillary artery.

Incidence of thyroid IMA artery in our population

To find out the incidence of thyroid ima artery in our population. An exploratory study. This study was conducted in a private hospital and Nishtar Hospital Multan. Study was conducted from 15 Jan to 25 September 2012. All the patients with the goiter and who were euthyroid presenting to the Nishatr Hospital and private hospital [Khursheed Rafiq Hospital] in Multan were included in study.Patients with tumors and huge retrostemal goiter were excluded from the study.During surgery of thyroid, meticulous dissection was done to identify the thyroid ima artery and incidence was recorded. A total no of 87 patients were included in the study. Out these 7 were excluded due to the huge goiter with difficult surgery. Out of remaining 80 pts, 65 [80%] were females on 15 [20%] were females, [ratio of female to male 4.3: l].The mean age of the patients was 45 years [from 70 years to 20 years] The thyroid ima artery was found in 4 pts only [5%].All the patients were females It means that incidence of this artery in females is more than males.It may be due to the more incidence of goiter in females [80%] than males as this study was conducted only patients suffering from goiter. In both patients this artery was supplying the isthmus of the thyroid gland. This was of adequate size. Inferior thyroid artery was also present in both cases. The incidence of thyroid ima artery was recorded to be 4% in our population

Arteria mediana persistente (AMP) bilateral de gran calibre en sujeto asintomático / High-caliber persistent bilateral median artery in asymptomatic

Se describe hallazgo en hombre de 22 años, asintomático, sano, de Arteria Mediana Persistente (AMP) bilateral de gran calibre asociada a un nervio median bífido (NMB) en una de las muñecas. La arteria mediana puede persistir hasta la adultez, acompañando al nervio por el túnel carpiano. Es una variante frecuente, suele ser bilateral y se asocia usualmente a NMB. La presencia de AMP puede asociarse a STC agudo secundario a trombosis y a STC crónicos por conflicto espacial. Sorprende el carácter asintomático de nuestro paciente a pesar del gran calibre de sus AMP. Sugerimos realizar, previo a cirugía o infiltración por STC, una ultrasonografía para adaptar tratamiento y evitar complicaciones.

We describe two high-caliber persistent median arteries (MPA) in an asymptomatic 22 year old healthy man, one of them between a bifid median nerve (BMN). The median artery may persist into adulthood, accompanying the median nerve through the carpal tunnel. It is a frequent anatomic variant, usually bilateral, regularly associated to BMN. The presence of MPA may be associated with acute carpal tunnel syndrome (CTS) secondary to thrombosis and chronic CTS probably due to spatial conflict. In this case, calls attention the lack of symptomatology despite the great size of MPA. We suggest performing prior to any surgery or infiltration of corticosteroids for CTS, an ultrasonographic study to avoid surgical complications.

Aneurisma verdadero en arteria ciática persistente: caso clínico / Persistent sciatic artery aneurysm: a case report

We report the case of a 71 years old female patient, who had a partially thrombosed true aneurysm in a persistent sciatic artery (PSA), treated in the Surgery Department of Hospital Dr. Eduardo Pereira of Valparaiso. The sciatic artery arises from the umbilical artery and during early embryological state is the main blood supply of the lower limbs. Later, the superficial femoral artery appears with the subsequent progressive involution of the sciatic artery. PSA is a rare congenital vascular anomaly that occurs when sciatic artery fails to regress during fetal development. This is associated with superficial femoral artery hipoplasia and the PSA becomes the dominant arterial inflow to the lower limb. This anatomic abnormality may be bilateral and can remain asymptomatic for many years, however, it has been described aneurysmal degeneration, like in this case, symptoms of sciatic nerve compression, aneurysm thrombosis and distal embolization.

Se reporta el caso de una paciente de 71 años, que presenta un aneurisma verdadero, parcialmente trombosado, en una Arteria Ciática Persistente (ACP), tratada en el Servicio de Cirugía del Hospital Dr. Eduardo Pereira de Valparaíso. La arteria ciática se origina en la arteria umbilical y durante las primeras fases embriológicas es el principal aporte sanguíneo de la extremidad inferior. Posteriormente aparece la arteria femoral superficial y se produce la progresiva involución de la arteria ciática. La ACP constituye una rara anomalía y ocurre por la falta de desarrollo de la arteria femoral superficial. La ACP se origina en el adulto en la arteria hipogástrica, transcurre hacia la región glútea a través de la escotadura ciática y sigue hacia distal por la parte posterior del muslo continuándose después con la arteria poplítea. Se acompaña de un variable menor desarrollo del eje arterial anterior de la arteria ilíaca externa y femoral superficial. Esta anomalía anatómica puede ser bilateral y puede permanecer asintomática durante muchos años, sin embargo, se ha descrito la degeneración aneurismática, como en este caso, y síntomas por compresión del nervio ciático, trombosis del aneurisma y embolización distal.

Multiple arterial variations in the right upper limb of a caucasian male cadaver / Múltiples variaciones arteriales en el miembro superior derecho de un cadáver caucásico masculino

Anatomical variations of the arterial patterns in the upper limb have been describe in many anatomical studies, but the occurrence of four variations in a ipsilateral upper limb is rare. These arterial variations were observed in the right upper limb of a 65 -year old Caucasian male cadaver during routine dissection in the anatomy department, College of Medicine at the King Saud University, Riyadh. These arterial variations include: 1) a large common trunk of the axillary artery giving origin to subscapular artery, profunda brachii artery, common circumflex humoral artery and superior ulnar collateral artery, 2) superficial brachial artery; 3) superficial brachioulnar artery, and 4) the radialis indicis branch from superficial palmar arch. Appreciation of variations in the upper limb vessels is important due to increasing number of procedures both diagnostic and therapeutic as in breast cancer surgery, flap harvesting and arteriogaphy.

En numerosos estudios se han descrito las variaciones anatómicas de los patrones arteriales en el miembro superior, sin embargo, la aparición de cuatro variantes ipsilaterales en un miembro superior es poco frecuente. Estas variaciones arteriales fueron observadas en el miembro superior derecho de un cadáver caucásico masculino de 65 años de edad, durante la disección de rutina en el Departamento de Anatomía de la Facultad de Medicina de la Universidad de King Saud, en Riad. Estas variaciones arteriales incluyen: 1) un gran tronco común de la arteria axilar dando origen a las arterias subescapular, braquial profunda, braquial común y colateral ulnar superior; 2) la arteria braquial superficial; 3) la arteria braquioulnar superficial y 4) la rama radial del índice desde el arco palmar superficial. La observación de variaciones en los vasos del miembro superior es importante debido al número cada vez mayor de procedimientos diagnósticos y terapéuticos, como en la cirugía del cáncer de mama, la recolección de colgajos y arteriografías.

Three rare variations in the course of the gonadal artery / Tres raras variaciones en el trayecto de la arteria gonadal

The gonadal arteries, lateral branches of the abdominal aorta, usually arise distal to the renal vessels. Knowledge of the origin and course of them, particularly their relationships with renal vessels, are important for uncomplicated surgical procedures on the posterior abdominal wall. So the relationship of the testicular artery and renal vessels were studied in 80 cadavers in Calcutta National Medical College, India and detected three rare variations. We have discussed the possible clinical implications and embryological explanation with review of literature of those variations.

Las arterias gonadales, ramas laterales de la aorta abdominal, usualmente surgen distales a los vasos renales. El conocimiento del origen y trayecto de estas, particularmente sus relaciones con los vasos renales, son importantes para procedimientos quirúrgicos sin complicaciones en la pared posterior del abdomen. La relación de la arteria testicular y los vasos renales fueron estudiados en 80 cadáveres en la Escuela Nacional de Medicina de Calcuta, India y se detectaron tres variaciones raras. Se discuten las posibles implicancias clínicas y explicaciones embriológicas, con la revisión de la literatura de estas variaciones.

Enfermedad arterial periférica: índice tobillo/brazo: segunda parte / Peripheral arterial disease: ankle-arm index: part 2

En esta parte del artículo se describe la importancia del índice tobillo/brazo en el diagnóstico de ateromatosis arterial en territorios vasculares alejados de los miembros inferiores, y su utilidad en pacientes diabéticos.

Enfermedad arterial periférica: índice tobillo/brazo: primera parte / Peripheral arterial disease: ankle-arm index: part 1

En esta primera parte se presenta la epidemiología de esta enfermedad, fisiopatología, factores de riesgo, manifestación clínica, diagnóstico, y obtención del índice tobillo-brazo, considerado el mejor método diagnóstico no invasivo para su estudio.

The Incidence and Anatomy of Accessory Pudendal Arteries as Depicted on Multidetector-Row CT Angiography: Clinical Implications of Preoperative Evaluation for Laparoscopic and Robot-Assisted Radical Prostatectomy

OBJECTIVE: To help preserve accessory pudendal arteries (APAs) and to ensure optimal postoperative sexual function after a laparoscopic or robot-assisted radical prostatectomy, we have evaluated the incidence of APAs as detected on multidetector-row CT (MDCT) angiography and have provided a detailed anatomical description. MATERIALS AND METHODS: The distribution of APAs was evaluated in 121 consecutive male patients between February 2006 and July 2007 who underwent 64-channel MDCT angiography of the lower extremities. We defined an APA as any artery located within the periprostatic region running parallel to the dorsal vascular complex. We also subclassified APAs into lateral and apical APAs. Two radiologists retrospectively evaluated the origin, course and number of APAs; the final APA subclassification based on MDCT angiography source data was determined by consensus. RESULTS: We identified 44 APAs in 36 of 121 patients (30%). Two distinct varieties of APAs were identified. Thirty-three APAs (75%) coursed near the anterolateral region of the prostatic apex, termed apical APAs. The remaining 11 APAs (25%) coursed along the lateral aspect of the prostate, termed lateral APAs. All APAs originated from the internal obturator artery and iliac artery or a branch of the iliac artery such as the inferior vesical artery. The majority of apical APAs arose from the internal obturator artery (84%). Seven patients (19%) had multiple APAs. CONCLUSION: APAs are more frequently detected by the use of MDCT angiography than as suggested by previous surgical studies. The identification of APAs on MDCT angiography may provide useful information for the surgical preservation of APAs during a laparoscopic or robot-assisted radical prostatectomy.

[ survey of variation in obturator arteries]

The knowledge of surgeon from anatomical variation can inhance the recovery process of patients. Vascular variation and their accidental cutting during surgical procedure can produce some problems specially in arterial variation. So the anatomical and surgical department must not neglect to prapere some program in order to learn these variations to the students. The antero-inferior abdominal wall of white 35 years old man have dissected. It was revealed that the obturator artery is an accessory branch of inferior epigastric artery at the medial side of deep inguinal ring. Subsequently it descend medially, crossing the free margin of lacunar ligament to reach the obturator canal. This variation is potentially dangerous in operation of femoral hernia