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Aryl hydrocarbon hydroxylase activity was studied in cultured human lymphocytes using 3-methylcholanthrene, 1,2- benzanthracene, and 4'-bromoflavone as inducers. The substrates used to run the 60 minute assay were benzo(α)pyrene and diphenyloxazole. At the optimum bromoflavone concentration for induction of aryl hydrocarbon hydroxylase, the induced enzymatic activity compared favorably with that of aryl hydrocarbon hydroxylase induced by 3MC in a 96 hour lymphocyte culture using BP as the assay substrate. The whole cell human lymphocyte system was found to have as much or more activity in 20 ml vials using Joklik's-Modified Minimum Essential Medium at a pH optimum of 7.5 with no co-factor added as did the Roswell Park assay system. The whole cell assay showed that levels of aryl hydrocarbonhydroxylase inducibility in lumphocytes from smokers and non-smokers varied without regard to the subjects' smoking habits. The assay system also indicated that intact lymphocytes generate a similar group of benzo(α)pyrene metabolites as that produced by a hepatic microsomal preparation from C57B1/6J mice.

A coleta de dados por meio da anamnese e do exame físico é etapa indispensável para a implementação do Processo de Enfermagem; para realização do exame físico empregam-se as técnicas de inspeção, palpação, percussão e ausculta, que permitem confirmar padrões de normalidade ou a presença de alterações. É de interesse, neste estudo, o exame dos linfonodos, componentes que podem, a partir de suas alterações, nortear a terapêutica e as ações de enfermagem a serem executadas. Tais estruturas são avaliadas pelas técnicas de inspeção e palpação, além da anamnese. Considerando a necessidade de criação de estratégias cada vez mais interativas, baseadas na proposta da aprendizagem experiencial, este estudo experimental, randomizado, controlado e mascarado tem como objetivo avaliar a contribuição de um Módulo Instrucional na aquisição de conhecimentos sobre a avaliação de características de linfonodos, por estudantes de enfermagem. A intervenção educativa foi composta pela utilização de um módulo instrucional, formado por um protótipo de palpação e um instrumento-guia de registro. Participaram do estudo 68 estudantes dos cursos de graduação em enfermagem de uma instituição pública paulista que estavam cursando a disciplina de semiologia e semiotécnica. Em ambos os grupos (experimento e controle) foi realizada inicialmente a palpação dos linfonodos em um protótipo (A) seguindo-se o registro livre das características e número das estruturas avaliadas. O grupo controle seguiu para avaliação final, similar à inicial, em outro protótipo (C) utilizando o instrumento de registro livre. O grupo experimento foi submetido à intervenção educativa, que consistiu no manejo do módulo instrucional (protótipo B e instrumento-guia de registro dos dados) e, após, realizou a avaliação final, similar à do grupo controle. Após a avaliação final, o grupo controle foi apresentado à intervenção educativa. Por último, em ambos os grupos, os estudantes registraram sua opinião sobre a atividade educativa realizada. Utilizou-se para análise os registros realizados nas fases inicial e final; os dados foram categorizados e, para avaliar idade, curso e sexo, utilizou-se frequência, média, mediana e desvio-padrão; para verificar a interação entre os acertos das variáveis pelos grupos nos tempos, optou-se pelo modelo de regressão linear mista. A análise de interação entre os grupos permite concluir que o grupo experimento apresentou significativa diferença com relação ao grupo controle no acerto de tamanho (p <= 0,0001), consistência (p <= 0,0001), mobilidade (p <= 0,0001) e coalescência (p = 0,0021). Ainda, os estudantes avaliaram positivamente a atividade, destacando sua capacidade de relacionar a teoria com a prática, sua facilidade e boa representação da realidade. Os resultados positivos do grupo experimento, bem como a aceitação referida pelo público-alvo reforçam a utilização do módulo instrucional como estratégia de ensino complementar às aulas de semiologia e semiotécnica no ensino da avaliação de características de linfonodos / The data colleta through anamnesis and physical examination is an indispensable step for the implementation of the Nursing Process; to perform the physical examination are used the techniques of inspection, palpation, percussion and auscultation, which allow to confirm patterns of normality or the presence of changes. It is of interest, in this study, the examination of the lymph nodes, components that can, from their alterations, guide the therapeutics and the nursing actions to be performed. Such structures are evaluated by the techniques of inspection and palpation, in addition to anamnesis. Considering the need to create increasingly interactive strategies based on the proposal of experiential learning, this experimental, randomized, controlled and double blind study aims to evaluate the contribution of an Instructional Module in the acquisition of knowledge about the evaluation of lymph node characteristics, by nursing students. The educational intervention was composed by the use of an instructional module, formed by a prototype of palpation and a guide instrument of registration. The participants of the study were 68 undergraduate nursing students from a public institution in São Paulo who were attending the discipline of semiology and semitechnical. In both groups (experiment and control) the palpation of the lymph nodes was initially performed in a prototype (A) followed by the free registration of the characteristics and number of the structures evaluated. The control group followed for final evaluation, similar to the initial one, in another prototype (C) using the free registry instrument. The experimental group was submitted to the educational intervention, which consisted in the management of the instructional module (prototype B and instrument guide of data recording) and, afterwards, made the final evaluation, similar to that of the control group. After the final evaluation, the control group was presented to the educational intervention. Finally, in both groups, the students recorded their opinion about the educational activity performed. We used for analysis the records made in the initial and final phases; the data were categorized and, to evaluate age, course and sex, we used frequency, mean, median and standard deviation; to verify the interaction between the correctness of the variables by the groups in the times, we opted for the mixed linear regression model. The analysis of interaction between the groups allows to conclude that the experiment group presented a significant difference in relation to the control group in the variables size of the lymph node (P <= 0.0001), consistency (p <= 0.0001), mobility (p <= 0.0001) and coalescence (p = 0.0021). Still, the students positively evaluated the activity, highlighting their ability to relate theory to practice, its easy and good representation of reality. The positive results of the experiment group as well as the acceptance reported by the target public reinforce the use of the instructional module as a complementary teaching strategy to the semiology and semi-technical classes in teaching the evaluation of lymph node characteristics

Neste estudo investigamos os mecanismos reguladores associados à indução da inflamação pulmonar decorrente da /IR intestinal. A hipótese é que mediadores inflamatórios gerados no intestino, drenados pelo sistema linfático medeiam as repercussões pulmonares observadas na SDRA. Grupos de ratos foram submetidos à isquemia intestinal por meio da oclusão da artéria mesentérica superior (45 min) seguida da reperfusão intestinal por 2h. Grupos de ratos foram submetidos à obstrução do fluxo linfático (canulação do dueto torácico linfático, ou sua secção) previamente à indução da I/R intestinal. Os dados indicaram que a secção do dueto linfático torácico reduziu a atividade pulmonar de MPO (índice indireto de presença de neutrófilos), bem como a permeabilidade vascular (extravasamento do corante Azul de Evans) pulmonar e intestinal e aumento da atividade de LDH intestinal (índice de lesão tecidual). Sistemicamente, a ligação do dueto linfático antes da indução de l/R intestinal reduziu os níveis séricos de TNF-<font face=\"symbol\">a, IL- 1<font face=\"symbol\">b e elevou aqueles de IL-10, LTB4e TXB2. Ainda, observamos que a linfa coletada nesses animais é rica em TNF-<font face=\"symbol\">a, IL-1<font face=\"symbol\">b, IL-10, LTB4 e TXB2. O tratamento dos animais previamente à l/R intestinal com o inibidor de síntese de TNF-<font face=\"symbol\">a, pentoxifilina (PTX), reduziu a atividade de MPO pulmonar nos animais submetidos a l/R intestinal com o dueto linfático intaeto e a potencializou naqueles onde o dueto torácico linfático foi seccionado. A PTX reduziu o aumento de permeabilidade vascular pulmonar e intestinal em condições onde dueto linfático torácico foi mantido intacto. Por outro lado em animais l/R intestinal com o dueto linfático seccionado, a PTX não causou redução adicional da permeabilidade vascular, mas reduziu os níveis séricos de IL-1<font face=\"symbol\">b e aumentou os de LTB4, enquanto na linfa, o tratamento com PTX aumentou a concentração de IL-10 e LTB4 e reduziu a de IL-1<font face=\"symbol\">b e TXB2. A inibição não seletiva das NOS com o composto L-NAME causou aumento dos níveis séricos de TNF-<font face=\"symbol\">a, os quais foram reduzidos pela secção do dueto linfático. O bloqueio da geração do NO nos animais com dueto seccionado não alterou o perfil no soro de IL-10, mas elevou a concentração de IL-1<font face=\"symbol\">b. Ainda, na linfa dos animais tratados com L-NAME, houve aumento de IL-1<font face=\"symbol\">b, IL-10, LTB4 e TXB2 e redução de TNF-<font face=\"symbol\">a. Nossos dados ainda revelaram que o pulmão dos animais I/R intestinal gerou IL1<font face=\"symbol\">b e IL-10 quando o dueto linfático estava intacto, e que sua secção reduziu os níveis gerados dessas citocinas. A PTX reduziu a geração de IL-1<font face=\"symbol\">b e aumentou a IL-10 no pulmão.O L-NAME aumentou a IL-1<font face=\"symbol\">b e IL-10 nos animais com o dueto intacto e interrupção do fluxo linfático aumentou os níveis de IL-1<font face=\"symbol\">b. A I/R intestinal, em animais com o dueto intacto, aumentou, enquanto na vigência da obstrução do fluxo linfático, houve redução da expressão de ICAM-1, Mac-1 e E-selectina no pulmão. Finalmente, os dados apresentados neste estudo sugerem que eventos isquêmicos intestinais seguidos de sua reperfusão, induzem a geração de mediadores inflamatórios locais (intestino) os quais uma vez drenados pelo sistema linfático mesentérico são transportados pela linfa e atingem o pulmão. Nessas condições observa-se inflamação pulmonar e geração adicional de mediadores inflamatÓrios os quais são lançadas à circulação e concorrem para o desenvolvimento da inflamação sistêmica e eventualmente para a falência múltipla dos órgãos. / In this study we investigated the role of lymphatic system on the mechanisms associated to the induction of lung inflammation afier intestinal I/R in rats. The hypothesis ofthe study was that upon intestinal I/R, inflammatory mediators are generated in the intestine and once drained by mesenteric lyrnphatic system interfere with the lung homeostasis contributing to lung dysfunction observed in ARDS. To these purposes groups of rats were submitted to occlusion of superior mesenteric artery (45 min) followed by intestinal reperfusion during 2h when the rats were killed. Groups of rats were subjected to thoracic lymphatic duct ligation previously to induction of the intestinal I/R. The data showed that the thoracic duct ligation significantly reduced the increased pulmonary MPO activity and the augrnented vascular perrneability (extravasation of the Evans blue dye) in lung and intestine. In addition, thoracic duct ligation increased the intestinal activity of LDH. Systemically, the obstruction of lymph flow, leaded to reduction of TNF in serum of rats upon intestinal I/R and increased the levels of IL-1O, LTB4 and TXB2. Elevated levels of TNF-<font face=\"symbol\">a, IL-l<font face=\"symbol\">b), IL-1O, LTB4 and TXB2 were also found in lymph ofrats upon intestinal I/R. The treatment of the animals previously to the intestinal I/R induction with inhibitor of TNF-<font face=\"symbol\">a synthesis, pentoxyfilline (PTX), reduced the lung MPO activity upon lymphatic duct intact that was exacerbated by thoracic duct ligation. PTX treatment reduced the increased vascular permeability of the lung and intestine conditions in rats with lymphatic duct intact. On the other hand, when the thoracic duct was ligated, the PTX did not cause additional reduction of vascular permeability in both tissues , but reduced the serum levels of IL-1<font face=\"symbol\">b) and increased those of LTB4. Lymph of rats treated with PTX revealed an increased leveI of IL-10 and LTB4 and a reduced leveI of IL-<font face=\"symbol\">b) and TXB2. L-NAME treatment increased the serum levels of TNF-<font face=\"symbol\">a, which were reduced by the thoracic lymphatic duct ligation. The blockade of NO synthesis in rats with lymphatic duct ligation did not modify the IL-10 serum levels, but increased those of IL-1<font face=\"symbol\">b). Lymph of rats upon L-NAME treatment, an increased level of IL-1<font face=\"symbol\">b), IL-1O, LTB4 and TXB2 and a reduction of TNF-<font face=\"symbol\">a levels were detected. Pulmonary tissue of Iymphatic duct intact rats after intestinal I/R were increased the release of IL-1<font face=\"symbol\">b) and IL-10 whereas the thoracic duct ligation reduced the release of these cytokines. PTX treatment reduced the levels of IL-1<font face=\"symbol\">b) and increased the IL-10 in the lung. L-NAME treatment increased the IL-1<font face=\"symbol\">b) and IL-10 in lung of intact duct rats but the obstruction of lymph flow caused an increase release of IL-1<font face=\"symbol\">b levels. Intestinal I/R in intact duct rats, increased whereas the thoracic duct ligation reduced the pulmonary expression of ICAM-1, Mac-1 and E-selectin. In conclusion, our data suggest that intestinal I/R, induces the generation of local inflammatory mediators (intestine) which drained by the mesenteric lymphatic system are carried by the lymph and reach the lung. ln these conditions we observed pulmonary inflammation and additional generation of inflammatory mediators and eventually the development of the systemic inflammation. Our data support the view that lymphatic system play a role a path underlying the spread oflung and gut injury after intestinal I/R.

The lymphatic system is responsible for several vital roles in human body, one of which is maintaining fluid and protein balance. There is no central pump in the lymphatic system and the transport of fluid against gravity and adverse pressure gradient is maintained by the extrinsic and intrinsic pumping mechanisms. Any disruption of the lymphatic system due to trauma or injury can lead to edema. There is no cure for lymphedema partly because the knowledge of the function of the lymphatic system is lacking. Thus, a well-developed model of the lymphatic system is crucial to improve our understanding of its function. Here we used a lumped parameter approach to model a chain of lymphangions in series. Equations of conservation of mass, conservation of momentum, and vessel wall force balance were solved for each lymphangion computationally. Due to the lack of knowledge of the parameters describing the system in the literature, more accurate measurements of these parameters should be pursued to advance the model. Because of the difficulty of the isolated vessel and in-situ experiments, we performed a parameter sensitivity analysis to determine the parameters that affect the system most strongly. Our results showed that more accurate estimations of active contractile force and physiologic features of lymphangions, such as length/diameter ratios, should be pursued in future experiments. Also further experiments are required to refine the valve behavior and valve parameters.

Submitted by PRISCILA SILVA null (priscilasvet@gmail.com) on 2018-04-05T14:21:37Z No. of bitstreams: 1 Dissertação Priscila Silva.pdf: 1846233 bytes, checksum: 95363950f8300b574023fbfe2f7b3eb8 (MD5) / Approved for entry into archive by Alexandra Maria Donadon Lusser Segali null (alexmar@fcav.unesp.br) on 2018-04-06T10:29:16Z (GMT) No. of bitstreams: 1 silva_p_me_jabo.pdf: 1846233 bytes, checksum: 95363950f8300b574023fbfe2f7b3eb8 (MD5) / Made available in DSpace on 2018-04-06T10:29:16Z (GMT). No. of bitstreams: 1 silva_p_me_jabo.pdf: 1846233 bytes, checksum: 95363950f8300b574023fbfe2f7b3eb8 (MD5) Previous issue date: 2018-02-26 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A incidência de neoplasmas mamários em cadelas tem aumentado o seu diagnóstico juntamente com a sobrevida desses animais e a avaliação completa das mamas e anexos é fundamental para o diagnóstico adequado. Uma característica dos neoplasmas mamários é a grande capacidade de desenvolver metástase e os linfonodos regionais por serem responsáveis pela drenagem das mamas, desenvolvem um papel importante na disseminação de células tumorais, sendo um fator prognóstico negativo para os pacientes. O desenvolvimento de novas técnicas para detecção do linfonodo sentinela e identificação prévia de alterações contribuem positivamente na sobrevida do paciente. Todavia, a maioria dos métodos utilizados para o diagnóstico conclusivo são métodos invasivos. Sendo assim, este estudo prospectivo visou avaliar a sensibilidade e especificidade das técnicas ultrassonográficas para avaliação de linfonodos locoreginais em cadelas com tumores mamários (Modo-B, Doppler em cores e Elastografia Acoustic Radiation Force Impulse - ARFI), pela diferenciação da malignidade (livres, reativos e metastáticos) Linfonodos axilares (n = 96) e inguinais (n = 100) ipsilaterais de cadeias mamárias de 100 cadelas acometidas foram avaliados por meio da ultrassonografia modo-B (comprimento, altura, relação eixo curto/longo, forma, ecotextura e ecogenicidade), Doppler em cores (presença ou ausência de vascularização) e Elastografia ARFI (rigidez, padrão, deformabilidade, velocidade de cisalhamento e profundidade). As variáveis que obtiveram diferença significativa foram valor de corte, sensibilidade, especificidade, área sobre a curva e acurácia. A velocidade de cisalhamento obtida pela elastografia ARFI apresentou sensibilidade de 95%, especificidade de 87% e acurácia de 90% em linfonodos inguinais com metástase, com valor de corte > 2.5 m/s, e sensibilidade 100%, especificidade 94% e acurácia 90%, com valor de corte > 2,4m/s em axilares metastáticos, demonstrando ser um método adequado e não invasivo para detecção de linfonodos com metástase. Ao elastograma, a presença de estruturas neoplásicas mais rígidas (áreas avermelhadas) foram indicativas de malignidade, com as reativas com menor rigidez (áreas esverdeadas) e as normais (áreas azuladas) menos rígidas que as anteriores. Concluiu-se que a avaliação dos linfonodos por meio da elastografia ARFI é um preditor eficaz na detecção de linfonodos com metástase, reativos ou livres. Assim, a inclusão deste exame na clínica veterinária e oncologia é recomendada principalmente por ser uma técnica não invasiva, inócua e que pode melhorar o prognóstico do paciente. / The incidence of mammary neoplasms in bitches has increased their diagnosis along with a survival of the animals and a complete evaluation of the mammarys and appendages is fundamental for the proper diagnosis. A characteristic of mammary neoplasms is a great capacity to develop regional metaphors and lymph nodes because they are responsible for the production of breasts, they play an important role in the dissemination of tumor cells, being a negative prognostic factor for the patients. The development of new techniques for lymph node detection and the preventive identification of positive contributions to patient survival. However, most of the methods used for conclusive diagnosis are invasive methods. (B-mode, Doppler in nuclei and Acoustic Radiation Force Impulse Elastography - ARFI), by the difference in the literature, reactive and metastatic measurements of malignancy (lp, Doppler color and Elastography). Axillary lymph nodes (n = 96) and inguinal lymph nodes (n = 100) ipsilateral mammary chains of 100 bitches were reassessed by means of B-mode ultrasonography (length, height, short / long axis, shape, ecotexture and echogenicity), core Doppler (presence or absence of vascularization) and ARFI Elastography (stiffness, pattern, deformability, shear velocity and depth). The variables that obtained the significant difference have cut-off value, sensitivity, specificity, area over the curve and accuracy. The shear velocity obtained by ARFI elastography showed 95% sensitivity, 87% specificity and 90% accuracy in metastasis inguinal lymph nodes, with cutoff value> 2.5 m / s, and sensitivity 100%, specificity 94% and 90% accuracy, with cutoff value> 2.4 m / s in metastatic axillaries, proving to be an adequate and noninvasive method for the detection of lymph nodes with metastasis. Electrolytes, the presence of more rigid neoplastic structures, such as reactive ones with less stiffness (green areas) and as normal (bluish areas) less rigid than before. It was concluded that the evaluation of lymph nodes through elasticity. ARFI is an effective predictor for the detection of metastatic lymph nodes, either reactive or free. Thus, an inclusion of this examination in the veterinary clinic and oncology is recommended mainly because it is a noninvasive technique, innocuous and that can improve the prognosis of the patient.

Neste estudo investigamos os mecanismos reguladores associados à indução da inflamação pulmonar decorrente da /IR intestinal. A hipótese é que mediadores inflamatórios gerados no intestino, drenados pelo sistema linfático medeiam as repercussões pulmonares observadas na SDRA. Grupos de ratos foram submetidos à isquemia intestinal por meio da oclusão da artéria mesentérica superior (45 min) seguida da reperfusão intestinal por 2h. Grupos de ratos foram submetidos à obstrução do fluxo linfático (canulação do dueto torácico linfático, ou sua secção) previamente à indução da I/R intestinal. Os dados indicaram que a secção do dueto linfático torácico reduziu a atividade pulmonar de MPO (índice indireto de presença de neutrófilos), bem como a permeabilidade vascular (extravasamento do corante Azul de Evans) pulmonar e intestinal e aumento da atividade de LDH intestinal (índice de lesão tecidual). Sistemicamente, a ligação do dueto linfático antes da indução de l/R intestinal reduziu os níveis séricos de TNF-<font face=\"symbol\">a, IL- 1<font face=\"symbol\">b e elevou aqueles de IL-10, LTB4e TXB2. Ainda, observamos que a linfa coletada nesses animais é rica em TNF-<font face=\"symbol\">a, IL-1<font face=\"symbol\">b, IL-10, LTB4 e TXB2. O tratamento dos animais previamente à l/R intestinal com o inibidor de síntese de TNF-<font face=\"symbol\">a, pentoxifilina (PTX), reduziu a atividade de MPO pulmonar nos animais submetidos a l/R intestinal com o dueto linfático intaeto e a potencializou naqueles onde o dueto torácico linfático foi seccionado. A PTX reduziu o aumento de permeabilidade vascular pulmonar e intestinal em condições onde dueto linfático torácico foi mantido intacto. Por outro lado em animais l/R intestinal com o dueto linfático seccionado, a PTX não causou redução adicional da permeabilidade vascular, mas reduziu os níveis séricos de IL-1<font face=\"symbol\">b e aumentou os de LTB4, enquanto na linfa, o tratamento com PTX aumentou a concentração de IL-10 e LTB4 e reduziu a de IL-1<font face=\"symbol\">b e TXB2. A inibição não seletiva das NOS com o composto L-NAME causou aumento dos níveis séricos de TNF-<font face=\"symbol\">a, os quais foram reduzidos pela secção do dueto linfático. O bloqueio da geração do NO nos animais com dueto seccionado não alterou o perfil no soro de IL-10, mas elevou a concentração de IL-1<font face=\"symbol\">b. Ainda, na linfa dos animais tratados com L-NAME, houve aumento de IL-1<font face=\"symbol\">b, IL-10, LTB4 e TXB2 e redução de TNF-<font face=\"symbol\">a. Nossos dados ainda revelaram que o pulmão dos animais I/R intestinal gerou IL1<font face=\"symbol\">b e IL-10 quando o dueto linfático estava intacto, e que sua secção reduziu os níveis gerados dessas citocinas. A PTX reduziu a geração de IL-1<font face=\"symbol\">b e aumentou a IL-10 no pulmão.O L-NAME aumentou a IL-1<font face=\"symbol\">b e IL-10 nos animais com o dueto intacto e interrupção do fluxo linfático aumentou os níveis de IL-1<font face=\"symbol\">b. A I/R intestinal, em animais com o dueto intacto, aumentou, enquanto na vigência da obstrução do fluxo linfático, houve redução da expressão de ICAM-1, Mac-1 e E-selectina no pulmão. Finalmente, os dados apresentados neste estudo sugerem que eventos isquêmicos intestinais seguidos de sua reperfusão, induzem a geração de mediadores inflamatórios locais (intestino) os quais uma vez drenados pelo sistema linfático mesentérico são transportados pela linfa e atingem o pulmão. Nessas condições observa-se inflamação pulmonar e geração adicional de mediadores inflamatÓrios os quais são lançadas à circulação e concorrem para o desenvolvimento da inflamação sistêmica e eventualmente para a falência múltipla dos órgãos. / In this study we investigated the role of lymphatic system on the mechanisms associated to the induction of lung inflammation afier intestinal I/R in rats. The hypothesis ofthe study was that upon intestinal I/R, inflammatory mediators are generated in the intestine and once drained by mesenteric lyrnphatic system interfere with the lung homeostasis contributing to lung dysfunction observed in ARDS. To these purposes groups of rats were submitted to occlusion of superior mesenteric artery (45 min) followed by intestinal reperfusion during 2h when the rats were killed. Groups of rats were subjected to thoracic lymphatic duct ligation previously to induction of the intestinal I/R. The data showed that the thoracic duct ligation significantly reduced the increased pulmonary MPO activity and the augrnented vascular perrneability (extravasation of the Evans blue dye) in lung and intestine. In addition, thoracic duct ligation increased the intestinal activity of LDH. Systemically, the obstruction of lymph flow, leaded to reduction of TNF in serum of rats upon intestinal I/R and increased the levels of IL-1O, LTB4 and TXB2. Elevated levels of TNF-<font face=\"symbol\">a, IL-l<font face=\"symbol\">b), IL-1O, LTB4 and TXB2 were also found in lymph ofrats upon intestinal I/R. The treatment of the animals previously to the intestinal I/R induction with inhibitor of TNF-<font face=\"symbol\">a synthesis, pentoxyfilline (PTX), reduced the lung MPO activity upon lymphatic duct intact that was exacerbated by thoracic duct ligation. PTX treatment reduced the increased vascular permeability of the lung and intestine conditions in rats with lymphatic duct intact. On the other hand, when the thoracic duct was ligated, the PTX did not cause additional reduction of vascular permeability in both tissues , but reduced the serum levels of IL-1<font face=\"symbol\">b) and increased those of LTB4. Lymph of rats treated with PTX revealed an increased leveI of IL-10 and LTB4 and a reduced leveI of IL-<font face=\"symbol\">b) and TXB2. L-NAME treatment increased the serum levels of TNF-<font face=\"symbol\">a, which were reduced by the thoracic lymphatic duct ligation. The blockade of NO synthesis in rats with lymphatic duct ligation did not modify the IL-10 serum levels, but increased those of IL-1<font face=\"symbol\">b). Lymph of rats upon L-NAME treatment, an increased level of IL-1<font face=\"symbol\">b), IL-1O, LTB4 and TXB2 and a reduction of TNF-<font face=\"symbol\">a levels were detected. Pulmonary tissue of Iymphatic duct intact rats after intestinal I/R were increased the release of IL-1<font face=\"symbol\">b) and IL-10 whereas the thoracic duct ligation reduced the release of these cytokines. PTX treatment reduced the levels of IL-1<font face=\"symbol\">b) and increased the IL-10 in the lung. L-NAME treatment increased the IL-1<font face=\"symbol\">b) and IL-10 in lung of intact duct rats but the obstruction of lymph flow caused an increase release of IL-1<font face=\"symbol\">b levels. Intestinal I/R in intact duct rats, increased whereas the thoracic duct ligation reduced the pulmonary expression of ICAM-1, Mac-1 and E-selectin. In conclusion, our data suggest that intestinal I/R, induces the generation of local inflammatory mediators (intestine) which drained by the mesenteric lymphatic system are carried by the lymph and reach the lung. ln these conditions we observed pulmonary inflammation and additional generation of inflammatory mediators and eventually the development of the systemic inflammation. Our data support the view that lymphatic system play a role a path underlying the spread oflung and gut injury after intestinal I/R.

Mantle cell lymphoma (MCL) represents a heterogenous subtype of non-Hodgkin lymphoma (NHL), which can present in three distinct clinicopathologic variants: indolent type MCL, classic type MCL and blastoid type MCL. Despite the different variations, MCL, in general, is almost always associated with advanced-stage disease at diagnosis, with a strong predilection for significant extranodal involvement, usually to the bone marrow, CNS, peripheral blood and the gastrointestinal tract. However, the literature review reveals ocular involvement is a more rarely described extranodal site of involvement by MCL. Among the reported cases, the orbit was most commonly involved, followed by the eyelid and the lacrimal gland. We report a 63-year-old male who presented with a nine-month history of progressive symptoms of periorbital swelling and eyelid apraxia, causing bilateral visual disturbances. The patient was initially treated for presumed blepharospasm by his ophthalmologist with botulinum toxin injections; however, his periorbital edema continued to worsen, and he developed a discrete nodule in his right lower eyelid. Biopsy of the right eyelid nodule revealed classic type MCL with immunohistochemical testing positive for CD20, CD5, cyclin D1, SOX11 and Ki67 proliferative index of 40%. Fluorescence in situ hybridization (FISH) analysis detected (11;14) translocation. Mantle Cell Lymphoma International Prognostic Index Combined Biologic Index (MIPIb) score was calculated to be 6.5 points based on his age, ECOG performance status of 0-1, normal serum LDH, normal white blood cell count and elevated Ki67 proliferative index, stratifying patient into the high-risk group, with an estimated median overall survival of 37 months. Due to the bulky MCL involvement in the palpebral conjunctiva affecting his vision and eyelid function, he was immediately treated with radiation therapy to the bilateral orbits. PET-CT revealed adenopathy above and below the diaphragm. Bone marrow biopsy revealed focal involvement (5-10%) by MCL. Brain MRI revealed MCL infiltration in the bilateral orbits and lacrimal glands. Upper and lower endoscopy revealed multiple polyps positive for MCL. Given the advanced stage of the disease and his high-risk stratification, he was started on intensive induction chemotherapy with rituximab, dexamethasone, cytarabine, and carboplatin and received prophylactic intrathecal methotrexate. Systemic imaging after completion of four cycles of treatment revealed near resolution of the majority of the lymphadenopathy and all of the lymph nodes no longer demonstrated any significant metabolic activity. He completed two additional cycles of systemic chemotherapy and is currently being evaluated for autologous hematopoietic stem cell transplantation in complete remission-1 given his excellent response to treatment, his young age, high-risk disease at diagnosis, and good performance status. Despite the diffuse and extensive systemic disease, interestingly, our patient did not exhibit any constitutional or metastasis-associated symptoms and only presented with isolated periorbital swelling. Our case emphasizes the rare extranodal site of involvement by MCL and encourages all medical providers to remain cognizant of the varying ways in which MCL can present clinically.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive, rare malignancy. Exact incidence is unknown due to lack of diagnostic criteria. Typically, it involves skin and bone marrow and less likely, lymph nodes and visceral organs. We present a 76 year old male who started having a lesion on the left side of his back that was progressively enlarging. He initially started on antibiotic and topical medications for more than a month which did not help. Punch biopsy of the lesion was consistent with blastic plasmacytoid dendritic cell neoplasm, positive for CD2, CD5, CD7, CD43, weak CD58,Tdt, bcl-6. Patient denies fever, chills, night sweats, weight loss, change in appetite. Physical exam revealed a purplish lesion raised in the left upper back with multiple satellite-like purple lesions throughout the back. Laboratory showed white cell count 3.2 K/uL, hemoglobin 13 g/dL, platelet 135 K/uL. Bone marrow biopsy shows immature blastic neoplasm involving 15% of the bone marrow. Cytogenetics showed normal karyotype. Flow cytometry shows an immature lymphoid population with expression of CD4, CD56, and CD 123, negative for FLT3, IDH1, IDH2, NPM1 mutations. Positron emission tomography (PET) scan showed skin thickening with minimal FDG uptake in left posterior skin soft tissue of the chest near the shoulder with no other abnormal focal uptake and splenomegaly. BPDCN is a rare aggressive malignancy that is more common in older populations. The origin is from type 2 dendritic cells. Typical presentations are skin lesions, cytopenia, lymphadenopathy, and splenomegaly. Some of the cytological features of BPDCN include cloudy sky (blue cytoplasm with clearer areas), pseudopods, and microvacuoles. Confirmation of diagnosis is with immunophenotyping. Workup after diagnosis include complete blood count, liver and renal function, hepatitis panel, peripheral blood smear, bone marrow evaluation, systemic imaging, cerebrospinal fluid cytology. Treatment of BPDCN is challenging in this era. Most patients respond to chemotherapy, although they relapse. Tegraxofusp is suggested for remission induction therapy following allogeneic hematopoietic cell transplantation. Median overall survival is about one year. Only patients who underwent hematopoietic stem cell transplant had prolonged survival. Myelemia, old age and altered general state have worse prognosis.