Surgical options for lymphedema after gynecological cancer treatment: current trends and advances.

Lower leg lymphedema is an important complication after gynecological treatment that can severely affect the quality of life of long-term survivors of these malignancies. As a chronic and progressive disease, affected patients will require life-long therapy centered on compression. Although conventional compressive treatments can be effective, they are extremely burdensome and time-consuming for most patients and adherence is challenging. With advances in the field of reconstructive microsurgery, new procedures have been developed in the past decades to help these patients in their continuous care and have been offered at many oncological centers around the world as a first line of treatment. We performed a PubMed search using the Mesh terms 'Lymphedema/surgery' and 'Lower extremity' yielding a total of 508 articles. Of these, 35 articles were included for analysis. Articles that failed to provide a comprehensive analysis of outcomes following surgical treatment, studies examining treatment for upper limb lymphedema, primary lymphedema, or lower extremity lymphedema resulting from non-gynecologic etiologies, and studies that failed to have a minimum of 6 months follow-up were excluded. A comprehensive review of these 35 articles including over 1200 patients demonstrated large variability on the outcomes reported; however, an overall benefit from these procedures was found. Surgical options including lymphovenous anastomosis, vascularized lymph node transfers, and excisional procedures can be performed in patients with lower leg lymphedema, depending on staging and findings in indocyanine green lymphography. Surgical treatment of lymphedema is an effective option that can improve symptoms and quality of life of patients suffering from lymphedema following gynecologic cancers.

Hydroxymethylnitrofurazone lymphatic uptake with nanostructured lipid carrier after oral administration in rats.

Background: Leishmaniasis, caused by the protozoan Leishmania sp., infects phagocyte cells present in lymphatic organs. This study demonstrates the influence of nanostructured lipid carrier-loaded hydroxymethylnitrofurazone (NLC-NFOH) on lymphatic uptake using a chylomicron-blocking flow model in rats. Method: Lymphatic uptake of NFOH was assessed 1 h after oral administration of dimethyl sulfoxide with NFOH or NLC-NFOH with and without cycloheximide pretreatment. Result: Dimethyl sulfoxide with NFOH and NLC-NFOH showed NFOH serum concentrations of 0.0316 and 0.0291 µg/ml, respectively. After chylomicron blocking, NFOH was not detected. Conclusion: Despite log P below 5, NFOH was successfully taken up by the lymphatic system. Long-chain fatty acids and particle size might be main factors in these findings. NLC-NFOH is a promising and convenient platform for treating leishmaniasis via oral administration.

Tratamiento quirúrgico para reducción de volumen de linfedema de miembro inferior / Surgical Treatment for Volume Reduction of Lower Limb Lymphedema

Introducción: El linfedema de extremidades inferiores es la acumulación de fluido rico en proteínas en el intersticio como consecuencia del daño de vasos linfáticos. En el ámbito de la angiología se relaciona más frecuentemente con el tratamiento quirúrgico del cáncer. Los objetivos principales en el manejo del linfedema son limitar la morbilidad del paciente y mejorar la funcionalidad y la calidad de vida. Existen procedimientos que buscan prevenir el desarrollo del linfedema de extremidades inferiores. Una vez establecido, el tratamiento puede ser conservador y quirúrgico. El tratamiento quirúrgico incluye procedimientos fisiológicos (reconstructivos) y resectivos. El éxito depende de una buena selección de los pacientes y la realización de un tratamiento individualizado. Objetivo: Presentar el tratamiento quirúrgico utilizado para reducción de volumen de linfedema de miembro inferior izquierdo. Presentación del caso: Paciente masculino de 38 años, blanco, con antecedentes de diabetes mellitus tipo 2 de tres años de evolución, hipertensión arterial de 10 años de evolución y linfedema primario precoz desde hace 10 años en región del muslo del miembro inferior izquierdo. El paciente se ingresó días previos a la cirugía para realizar reposo venoso y fisioterapia (terapia física compleja). Se realizó, desde el punto de vista quirúrgico, una linfangiectomía atípica en la zona afectada. Conclusiones: Se logró la disminución del volumen de la extremidad y se mejoró su funcionabilidad(AU)

Introduction: Lymphedema of the lower limbs is the accumulation of protein-rich fluid in the interstitium as a result of lymphatic vessel damage. In the field of angiology, it is most frequently related to the surgical treatment of cancer. The main goals in the management of lymphedema are to limit the patient's morbidity, and to improve functionality and quality of life. There are procedures that seek to prevent the development of lymphedema of the lower limbs. Once established, treatment can be conservative and surgical. Surgical treatment includes physiological (reconstructive) and resective procedures. Success depends on good patient´s selection and individualized treatment. Objective: To present the surgical treatment used for volume reduction of lymphedema of the left lower limb. Case presentation: A 38-year-old white male patient with a history of type 2 diabetes mellitus for three years, hypertension for 10 years, and early primary lymphedema for 10 years in the thigh region of the left lower limb. The patient was admitted days prior to surgery due to venous rest and physiotherapy (complex physical therapy). From a surgical point of view, an atypical lymphangiectomy was performed in the affected area. Conclusions: A decrease in the volume of the limb was achieved and its functionality was improved(AU)

Outcomes of Chylothorax Nonoperative Management After Cardiothoracic Surgery: A Systematic Review and Meta-Analysis.

INTRODUCTION: Chylothorax after thoracic surgery is a severe complication with high morbidity and mortality rate of 0.10 (95% confidence interval [CI] 0.06 - 0.02). There is no agreement on whether nonoperative treatment or early reoperation should be the initial intervention. This systematic review and meta-analysis aimed to evaluate the outcomes of the conservative approach to treat chyle leakage after cardiothoracic surgeries. METHODS: A systematic review was conducted in PubMed®, Embase, Cochrane Library Central, and LILACS (Biblioteca Virtual em Saúde) databases; a manual search of references was also done. The inclusion criteria were patients who underwent cardiothoracic surgery, patients who received any nonoperative treatment (e.g., total parenteral nutrition, low-fat diet, medium chain triglycerides), and studies that evaluated chylothorax resolution, length of hospital stay, postoperative complications, infection, morbidity, and mortality. CENTRAL MESSAGE: Nonoperative treatment for chylothorax after cardiothoracic procedures has significant hospital stay, morbidity, mortality, and reoperation rates. RESULTS: Twenty-two articles were selected. Pulmonary complications, infections, and arrhythmia were the most common complications after surgical procedures. The incidence of chylothorax in cardiothoracic surgery was 1.8% (95% CI 1.7 - 2%). The mean time of maintenance of the chest tube was 16.08 days (95% CI 12.54 - 19.63), and the length of hospital stay was 23.74 days (95% CI 16.08 - 31.42) in patients with chylothorax receiving nonoperative treatment. Among patients that received conservative treatment, the morbidity event was 0.40 (95% CI 0.23 - 0.59), and reoperation rate was 0.37 (95% CI 0.27 - 0.49). Mortality rate was 0.10 (95% CI 0.06 - 0.02). CONCLUSION: Nonoperative treatment for chylothorax after cardiothoracic procedures has significant hospital stay, morbidity, mortality, and reoperation rates.

Does sentinel node mapping impact morbidity and quality of life in endometrial cancer?

OBJECTIVES: To evaluate the prevalence of post-operative complications and quality of life (QoL) related to sentinel lymph node (SLN) biopsy vs systematic lymphadenectomy in endometrial cancer. METHODS: A prospective cohort included women with early-stage endometrial carcinoma who underwent lymph node staging, grouped as follows: SLN group (sentinel lymph node only) and SLN+LND group (sentinel lymph node biopsy with addition of systematic lymphadenectomy). The patients had at least 12 months of follow-up, and QoL was assessed by European Organization for Research and Treatment of Cervical Cancer Quality of Life Questionnaire 30 (EORTC-QLQ-C30) and EORTC-QLQ-Cx24. Lymphedema was also assessed by clinical evaluation and perimetry. RESULTS: 152 patients were included: 113 (74.3%) in the SLN group and 39 (25.7%) in the SLN+LND group. Intra-operative surgical complications occurred in 2 (1.3%) cases, and all belonged to SLN+LND group. Patients undergoing SLN+LND had higher overall complication rates than those undergoing SLN alone (33.3% vs 14.2%; p=0.011), even after adjusting for confound factors (OR=3.45, 95% CI 1.40 to 8.47; p=0.007). The SLN+LND group had longer surgical time (p=0.001) and need for admission to the intensive care unit (p=0.001). Moreover, the incidence of lymphocele was found in eight cases in the SLN+LND group (0 vs 20.5%; p<0.001). There were no differences in lymphedema rate after clinical evaluation and perimetry. However, the lymphedema score was highest when lymphedema was reported by clinical examination at 6 months (30.1 vs 7.8; p<0.001) and at 12 months (36.3 vs 6.0; p<0.001). Regarding the overall assessment of QoL, there was no difference between groups at 12 months of follow-up. CONCLUSIONS: There was a higher overall rate of complications for the group undergoing systematic lymphadenectomy, as well as higher rates of lymphocele and lymphedema according to the symptom score. No difference was found in overall QoL between SLN and SLN+LND groups.

Revisiting the neuroinflammation hypothesis in Alzheimer's disease: a focus on the druggability of current targets.

Alzheimer's disease (AD) is the most common form of neurodegenerative disease and disability in the elderly; it is estimated to account for 60%-70% of all cases of dementia worldwide. The most relevant mechanistic hypothesis to explain AD symptoms is neurotoxicity induced by aggregated amyloid-ß peptide (Aß) and misfolded tau protein. These molecular entities are seemingly insufficient to explain AD as a multifactorial disease characterized by synaptic dysfunction, cognitive decline, psychotic symptoms, chronic inflammatory environment within the central nervous system (CNS), activated microglial cells, and dysfunctional gut microbiota. The discovery that AD is a neuroinflammatory disease linked to innate immunity phenomena started in the early nineties by several authors, including the ICC´s group that described, in 2004, the role IL-6 in AD-type phosphorylation of tau protein in deregulating the cdk5/p35 pathway. The "Theory of Neuroimmunomodulation", published in 2008, proposed the onset and progression of degenerative diseases as a multi-component "damage signals" phenomena, suggesting the feasibility of "multitarget" therapies in AD. This theory explains in detail the cascade of molecular events stemming from microglial disorder through the overactivation of the Cdk5/p35 pathway. All these knowledge have led to the rational search for inflammatory druggable targets against AD. The accumulated evidence on increased levels of inflammatory markers in the cerebrospinal fluid (CSF) of AD patients, along with reports describing CNS alterations caused by senescent immune cells in neuro-degenerative diseases, set out a conceptual framework in which the neuroinflammation hypothesis is being challenged from different angles towards developing new therapies against AD. The current evidence points to controversial findings in the search for therapeutic candidates to treat neuroinflammation in AD. In this article, we discuss a neuroimmune-modulatory perspective for pharmacological exploration of molecular targets against AD, as well as potential deleterious effects of modifying neuroinflammation in the brain parenchyma. We specifically focus on the role of B and T cells, immuno-senescence, the brain lymphatic system (BLS), gut-brain axis alterations, and dysfunctional interactions between neurons, microglia and astrocytes. We also outline a rational framework for identifying "druggable" targets for multi-mechanistic small molecules with therapeutic potential against AD.

Linfoma em cão da raça cane corso: relato de caso / Lymphoma in a cane corso dog: case report / Linfoma en un perro cane corso: relato de un caso

Os linfócitos são células de defesa do organismo que funcionam como barreira contra infecções e células cancerígenas, elas circulam pelo sistema linfático e estão presentes por todo o organismo do animal, podem se proliferar de forma maligna, caracterizando o linfoma. Acometem em sua maioria, cães de raças de grande porte, animais de meia idade e idosos. Sendo uma doença de etiologia desconhecida, vários fatores podem contribuir para sua evolução, como deficiências autoimunes, bem como hábitos alimentares ao longo da vida do animal, ou até por predisposição genética. O presente relato de caso, tem o objetivo de mostrar a evolução gradual da doença, quais sinais clínicos o animal poderá apresentar, e como os exames laboratoriais podem nos auxiliar em seu diagnóstico.(AU)

The lymphocytes are defense cells of the body that act as a barrier against infection and cancer cells, they circulate through the lymphatic system and are present throughout the animal's body, and can proliferate in a malignant way, characterizing the lymphoma. They mostly affect large breed dogs, middle-aged and elderly animals. Being a disease of unknown etiology, several factors may contribute to its evolution, such as autoimmune deficiencies, as well as food habits throughout the animal's life, or even genetic predisposition. The present case report has the objective of showing the gradual evolution of the disease, which clinical signs the animal may present, and how laboratory tests can help us in its diagnosis.(AU)

Los linfocitos son células de defensa del organismo que actúan como barrera contra infecciones y células cancerígenas, circulan por el sistema linfático y están presentes en todo el organismo del animal, pudiendo proliferar de forma maligna, caracterizando el linfoma. Afectan sobre todo a perros de razas grandes, animales de mediana edad y ancianos. Siendo una enfermedad de etiología desconocida, varios factores pueden contribuir a su evolución, como deficiencias autoinmunes, así como hábitos alimentarios a lo largo de la vida del animal, o incluso predisposición genética. El presente caso clínico tiene como objetivo mostrar la evolución gradual de la enfermedad, qué signos clínicos puede presentar el animal y cómo las pruebas de laboratorio pueden ayudarnos en su diagnóstico.(AU)

Outcomes of Chylothorax Nonoperative Management After Cardiothoracic Surgery: A Systematic Review and Meta-Analysis

ABSTRACT Introduction: Chylothorax after thoracic surgery is a severe complication with high morbidity and mortality rate of 0.10 (95% confidence interval [CI] 0.06 - 0.02). There is no agreement on whether nonoperative treatment or early reoperation should be the initial intervention. This systematic review and meta-analysis aimed to evaluate the outcomes of the conservative approach to treat chyle leakage after cardiothoracic surgeries. Methods: A systematic review was conducted in PubMed®, Embase, Cochrane Library Central, and LILACS (Biblioteca Virtual em Saúde) databases; a manual search of references was also done. The inclusion criteria were patients who underwent cardiothoracic surgery, patients who received any nonoperative treatment (e.g., total parenteral nutrition, low-fat diet, medium chain triglycerides), and studies that evaluated chylothorax resolution, length of hospital stay, postoperative complications, infection, morbidity, and mortality. Central Message Nonoperative treatment for chylothorax after cardiothoracic procedures has significant hospital stay, morbidity, mortality, and reoperation rates. Results: Twenty-two articles were selected. Pulmonary complications, infections, and arrhythmia were the most common complications after surgical procedures. The incidence of chylothorax in cardiothoracic surgery was 1.8% (95% CI 1.7 - 2%). The mean time of maintenance of the chest tube was 16.08 days (95% CI 12.54 - 19.63), and the length of hospital stay was 23.74 days (95% CI 16.08 - 31.42) in patients with chylothorax receiving nonoperative treatment. Among patients that received conservative treatment, the morbidity event was 0.40 (95% CI 0.23 - 0.59), and reoperation rate was 0.37 (95% CI 0.27 - 0.49). Mortality rate was 0.10 (95% CI 0.06 - 0.02). Conclusion: Nonoperative treatment for chylothorax after cardiothoracic procedures has significant hospital stay, morbidity, mortality, and reoperation rates.

Chronic progressive lymphoedema in a Friesian horse: clinical aspects and diagnostic approach - case report / [Linfedema progressivo crônico em um cavalo Friesian: aspectos clínicos e abordagem diagnóstica - relato de caso]

Chronic Progressive Lymphoedema (CPL) is a disabling disease of draft horses that affects lymphatic system function typically in the distal limbs. Deformities of distal limbs, especially of the pastern, with fibrosis and skin nodular lesions are consequences of disease progression. A 15-year-old Friesian stallion presented for evaluation with history of forelimb enlargement and nodule formations distal to the carpus for four years. Simple radiographs showed soft tissue nodular lesions and venous contrasted radiography showed intense enlargement of II common digital palmar vein of both forelimbs. Tissue culture tests revealed Streptococcus equi and Proteus mirabilis isolation and skin scraping test identified Chorioptes bovis mites. Histological examination revealed perivasculitis and lymph vessels distention. History, clinical and histological findings, and complementary exams suggested CPL diagnosis. We were unable to find previously published cases describing this disease in Brazil, where the increasing number of draft horses requires attention to this problem. The correct and early diagnosis substantially delays disease progression. Therefore, we highlight the need for nationwide propagation of these data to ensure better diagnosis and early treatment of future CPL cases.

O linfedema crônico progressivo (LCP) é uma enfermidade incapacitante de cavalos de tração que afeta o sistema linfático e se manifesta especialmente na região distal dos membros. A progressão da doença resulta em deformações na região distal dos membros, especialmente na quartela, com fibrose e lesões nodulares na pele. Foi atendido um garanhão da raça Friesian, de 15 anos de idade, com histórico de aumento de volume, nodulações e deformações na região distal dos membros torácicos, com início há aproximadamente quatro anos. Ao exame radiográfico simples, foram identificadas nodulações na pele e no subcutâneo e, ao exame venoso contrastado, identificou-se marcante dilatação II veia digital palmar comum em ambos os membros torácicos. Foi isolado Streptococcus equi e Proteus mirabilis ao cultivo tecidual e identificou-se sarna do tipo corióptica ao raspado de pele. No exame histopatológico, foram identificadas perivasculite e dilatação de vasos linfáticos. Os achados clínicos, histórico, de raça do animal e os exames complementares direcionaram o diagnóstico para o LCP. A pesquisa da literatura nacional não revelou descrições clínicas dessa enfermidade, mas, devido ao aumento do número de animais de tração no país nos últimos anos, a descrição dessa enfermidade se torna importante. O diagnóstico correto e precoce é necessário para retardar a progressão da doença. Nesse sentido, ressalta-se a relevância da divulgação nacional desses achados, a fim de contribuir para o diagnóstico precoce e permitir o retardo da evolução da doença.

Malformaciones linfáticas abdominales en una población pediátrica: experiencia en un centro de referencia de Medellín, Colombia / Abdominal lymphatic malformations in a pediatric population: Experience in a referral center in Medellín, Colombia

Introducción. Los linfangiomas son anormalidades benignas del sistema linfático, que corresponden a dilataciones quísticas de estos vasos y se localizan especialmente en el cuello. Solo el 10 % de todas estas malformaciones se encuentran en el abdomen y presentan síntomas variables de acuerdo al tamaño y su ubicación especifica, siendo el dolor abdominal el principal síntoma. Métodos. Se presentan cinco pacientes pediátricos con malformaciones linfáticas abdominales. Se describen su cuadro clínico, localización, tratamiento y la experiencia en el manejo de dicha patología en un hospital de referencia. Resultados. Los métodos más apropiados para hacer una aproximación diagnóstica son la ecografía, la tomografía computarizada y la resonancia nuclear magnética. Dentro de las opciones descritas para el tratamiento están la farmacológica, la escleroterapia y la resección quirúrgica, tanto por vía abierta como por laparoscopia. Conclusión. Existe una variedad de métodos para realizar la resección de los linfangiomas abdominales, pero la cirugía sigue siendo la más efectiva, especialmente cuando se cuenta con la laparoscopia como una herramienta terapéutica.

Introduction. Lymphangiomas are benign abnormalities of the lymphatic system, which correspond to cystic dilations of these vessels and are located especially in the neck. Only 10% of all these malformations are found in the abdomen and present variable symptoms according to size and their specific location, with abdominal pain being the main symptom. Methods. Five pediatric patients with abdominal lymphatic malformations are presented. Their clinical presentation, location, treatment and experience in the management of this pathology in a referral hospital are described. Results. The most appropriate methods to make a diagnostic approach are ultrasound, computed tomography and magnetic resonance imaging. Among the options described for treatment are pharmacological, sclerotherapy and surgical resection, both open and laparoscopic. Conclusion. There are a variety of methods for resecting abdominal lymphangiomas, but surgery remains the most effective, especially when laparoscopy is used as a therapeutic tool.

Terapia complexa descongestiva no tratamento de linfedema pós-mastectomia / Descongestive complex therapy in the treatment of lymphedema after mastectomy

Introdução: O linfedema é a complicação mais frequente no pós-operatório do câncer de mama. Objetivo: Identificar a efetividade do uso da Terapia Complexa Descongestiva (TCD) na redução do volume e no tratamento intensivo do linfedema em pacientes submetidas ao procedimento cirúrgico com esvaziamento axilar devido ao câncer de mama. Métodos: Trata-se de uma revisão sistemática, para o qual foram consultados os bancos de dados Bireme e Pubmed, utilizando artigos científicos em português e inglês de revistas indexadas nas bases de dados Medline, Scielo, Lilacs, Register of Controlled Trials (Cochrane Central) e Physiotherapy Evidence Database (PEDro), publicados entre os anos de 2004 e 2019. Para a construção do trabalho foram incluídos estudos que estivessem disponíveis na íntegra, que a população alvo fosse composta por mulheres submetidas ao procedimento cirúrgico devido ao câncer de mama, com esvaziamento axilar, que apresentassem linfedema e que incluíssem em seus tratamentos, um protocolo fisioterapêutico de TCD. Também de forma independente, foi avaliada a qualidade metodológica dos estudos selecionados com a Escala de Qualidade de JADAD. Resultados: Atualmente, o padrão-ouro dentre as principais técnicas fisioterapêuticas utilizadas para o tratamento do linfedema é a TCD, a qual é composta por drenagem linfática manual, cuidados com a pele e unhas, bandagem de compressão e exercícios terapêuticos. Conclusão: A TCD é considerada o método mais utilizado e eficiente na redução do volume e no tratamento intensivo do linfedema pósmastectomia. (AU)

Introduction: The lymphedema is the most common postoperative complication of breast cancer. Objective: The present study aims to identify the effectiveness of the use of Complex Decongestive Therapy (CDT) in reducing volume and intensive treatment of lymphedema in patients undergoing axillary emptying due to breast cancer. Methods: This was a systematic review, for which Bireme and Pubmed databases were consulted, using scientific articles in Portuguese and English from journals indexed in Medline, Scielo, Lilacs, Register of Controlled Trials (Cochrane Central) databases and Physiotherapy Evidence Database (PEDro), all of them published between the years 2004 to 2019. For the construction of this study, we included articles available in full, with a target population consisting of women undergoing the surgical procedure due to breast cancer, with axillary emptying, who presented lymphedema and who included in their treatments a physical therapy protocol of CDT. Also, independently, the methodological quality of the studies selected was evaluated using the JADAD Quality Scale. Results: Currently, the gold standard among the main physiotherapeutic techniques used for the treatment of lymphedema is CDT, which consists of manual lymphatic drainage, skin and nail care, compression bandaging and therapeutic exercises. Conclusion: The CDT is considered the most used and efficient method for volume reduction and intensive treatment of post-mastectomy lymphedema. (AU)

Nanostructured lipid carrier containing hydroxymethylnitrofurazone: preparation, characterization and in vitro and in vivo evaluation of leishmanicidal activity / Carreador lipídico nanoestruturado contendo hidroximetilnitrofural: preparação, caracterização físico-química e avaliação in vitro e in vivo da atividade leishmanicida

Leishmaniasis, a neglected tropical disease (NTD), is a set of diseases caused by obligatory parasitic protozoa of the genus Leishmania. And it has cutaneous and visceral eishmaniasis as its main forms. Treatment includes pentavalent antimonials. These drugs have several disadvantages, such as the need for parenteral administration, use of high dosages, long duration of treatment, severe toxicity, resistance and variable efficacy. The candidate for hydroxymethylnitrofural drug (NFOH), a prodrug derived from nitrofural, showed high activity in cell cultures infected with Trypanosoma cruzi and less toxicity when compared to nitrofural. Due to its low solubility in water and reduced bioavailability, NFOH has failed the in vivo efficacy tests. Nanostructured drug delivery systems have the potential to overcome these challenges due to their evident advantages: greater therapeutic efficacy, less toxicity, modified drug release and increased gastrointestinal absorption of drugs with low water solubility. The objective of this project will be the preparation and evaluation of the physicochemical characteristics of a nanostructured lipid carrier containing hydroxymethylnitrofural (NLC-NFOH). The NFOH showed the highest solubility in Miglyol® 840 among the tested liquid lipids. For solid lipids, Gelucire® 50/13 and Precirol® ATO5 proved to be more suitable for the solubilization of NFOH. The optimized NLC-NFOH consisted of these three lipids. These lipids were selected using a quick Technobis Crystal 16TM methodology, microscopy and DSC. Different lipid selection tools provided scientific knowledge relevant to the development of NLC. The NLC-NFOH had an average z of 198.6 ± 5.4 nm, a PDI of 0.11 ± 0.01 and a zeta potential of -13.7 ± 0.7 mV. This study allowed a design space development approach of the first NLC-NFOH with the potential to treat leishmaniasis orally. The development of a sensitive bioanalytical method using HPLC and evaluation of some analytical figures of merit for the validation allowed the quantification of NFOH and NF. The bioanalytical method for analysis of NFOH and NF use Zorbax SB-C18, 5µm, (4.6x250mm) HPLC column. The mobile phase was consisted of acetonitrile:water (20:80 v/v) with flow rate of 1.2 ml/min, at UV detection of 370 nm. The linearity of NFOH and NF was found in the range 0.0253.0 µg/ml with a correlation coefficient of r > 0.98. The precision was 2.44 to 13.77% for NFOH and 2.61 to 18.42%; the accuracy was 2.66 to 14.28% for NFOH and 2.09 to 19.06% for NF. The method showed to be suitable for effectively evaluation of NFOH is serum. NLC-NFOH (2.8 mg/kg) was administered to animals by gavage, and the blocking flow of the chylomicrons model was performed with an intraperitoneal injection of cycloheximide. The presence of NFOH in serum was evaluated with and without cycloheximide. The cytotoxicity assay of NLC-NFOH and blank-NLC showed more than 90% viable cells at the maximum concentration used (2560 µM). NFOH and NF were detected at 1h after the gavage of DMSO-NFOH or NLC-NFOH, without the pretreatment with cycloheximide. The concentration found for DMSO-NFOH and NLC-NFOH were 0.0316 and 0.0291 µg/mL, respectively. The NLC presented the NFOH absorption by the lymphatic system, demonstrated by blocking chylomicrons flow

A leishmaniose, uma doença tropical negligenciada (DTN), é um conjunto de doenças causadas por protozoários parasitas obrigatórios do gênero Leishmania. E tem como formas principais a leishmaniose cutânea e visceral. O tratamento inclui antimoniais pentavalentes. Esses fármacos apresentam várias desvantagens, como necessidade de administração parenteral, uso de altas dosagens, longa duração do tratamento, toxicidade grave, resistência e eficácia variável. O candidato ao fármaco hidroximetilnitrofural (NFOH), um pró-fármaco derivado do nitrofural, apresentou alta atividade em culturas de células infectadas pelo Trypanosoma cruzi e menor toxicidade quando comparado ao nitrofural. Devido à sua baixa solubilidade em água e biodisponibilidade reduzida, o NFOH falhou nos testes de eficácia in vivo. Os sistemas nanoestruturados de liberação de fármacos têm potencial para superar esses desafios devido às suas vantagens evidentes: maior eficácia terapêutica, menor toxicidade, liberação modificada do fármaco e aumento da absorção gastrointestinal de fármacos com baixa solubilidade em água. O objetivo deste projeto será a preparação e avaliação das características físico-químicas de um carreador lipídico nanoestruturado contendo hidroximetilnitrofural (NLC-NFOH). O NFOH apresentou a maior solubilidade no Miglyol® 840 entre os lipídios líquidos testados. Para lipídios sólidos, Gelucire® 50/13 e Precirol® ATO5 se mostraram mais adequados para a solubilização de NFOH. O NLC-NFOH otimizado consistiu desses três lipídios. Esses lipídios foram selecionados usando Technobis Crystal 16TM, microscopia e DSC. Diferentes ferramentas de seleção de lipídios forneceram conhecimento científico relevante para o desenvolvimento de NLC. O NLC-NFOH teve z-average de 198,6 ± 5,4 nm, PDI de 0,11 ± 0,01 e potencial zeta de -13,7 ± 0,7 mV. Este estudo permitiu o desenvolvimento por abordagem de Design Space do primeiro NLC-NFOH com potencial para tratar a leishmaniose por via oral. O desenvolvimento de um VIII método bioanalítico sensível utilizando HPLC e a avaliação de algumas figuras analíticas de mérito para a validação permitiram a quantificação de NFOH e NF em soro. O método bioanalítico para análise de NFOH e NF usou coluna de HPLC Zorbax SB-C18, 5 µm, (4,6 x 250 mm). A fase móvel foi constituída por acetonitrila: água (20:80 v / v) com vazão de 1,2 ml / min, com detecção no UV de 370 nm. A linearidade de NFOH e NF foi encontrada na faixa de 0,0253,0 µg / ml com um coeficiente de correlação de r> 0,98. A precisão foi de 2,44 a 13,77% para NFOH e 2,61 a 18,42%; a precisão foi de 2,66 a 14,28% para NFOH e 2,09 a 19,06% para NF. O método mostrou-se adequado para avaliação efetiva do NFOH no soro. NLC-NFOH (2,8 mg / kg) foi administrado aos animais por gavagem, e o modelo de bloqueio do fluxo de quilomícrons foi realizado com injeção intraperitoneal de cicloheximida. A presença de NFOH no soro foi avaliada com e sem cicloheximida. O ensaio de citotoxicidade de NLC-NFOH e brancoNLC mostrou mais de 90% de células viáveis na concentração máxima utilizada (2560 µM). NFOH e NF foram detectados 1h após a gavagem de DMSO-NFOH ou NLC-NFOH, sem o pré-tratamento com cicloheximida. As concentrações encontradas para DMSO-NFOH e NLC-NFOH foram 0,0316 e 0,0291 µg / mL, respectivamente. O NLC apresentou a absorção do NFOH pelo sistema linfático, demonstrada pelo bloqueio do fluxo dos quilomícrons

Contribution of an instructional module for lymph node evaluation: An experiment / Contribuição de um módulo instrucional para avaliação de linfonodos: um experimento / Contribución de un módulo instruccional para la evaluación de ganglios linfáticos: experimento

Objective: to evaluate the contribution of an instructional module identifying the number and characteristics of lymph nodes by undergraduate nursing students. Method: an experimental, randomized, controlled and masked study using an instructional module for intervention. The 68 students who made up the control group or the experimental group performed the prototype lymph node palpation in the initial and final phases, following the free registration of the characteristics and number of these structures. Between the phases, the instructional module (palpation prototype and a registration guide instrument) was applied to the experimental group. Descriptive statistics and mixed linear regression were used for analysis. Results: the experimental group showed greater accuracy (p<0.05) in the evaluation of the size, consistency, mobility and coalescence of the lymph nodes in the final phase when compared to the control; it also showed more chances to correctly evaluate the consistency ( OR 45,26; 95% CI<7,74>‡<264.54> p<0.0001), mobility (OR 55.95; CI 95% 12.45 - 251.60; p<0.0001) and size (OR 25.64; CI 95% 3.92 - 160.2; p=0.0002) of the lymph nodes. Conclusion: the results reinforce the contribution of the instructional module to increase the knowledge of nursing students about the evaluation of lymph nodes.

Objetivo: avaliar a contribuição de um módulo instrucional para a identificação do número e das características de linfonodos por estudantes de graduação em enfermagem. Método: estudo experimental, aleatorizado, controlado e mascarado utilizando para intervenção um módulo instrucional. Os 68 estudantes que compuseram o grupo controle ou o grupo experimento realizaram nas fases inicial e final a palpação dos linfonodos em protótipo, seguindo-se o registro livre das características e número dessas estruturas. Ao grupo experimento foi aplicado, entre as fases, o módulo instrucional (protótipo de palpação e um instrumento-guia de registro). Para análise empregou-se estatística descritiva e regressão linear mista. Resultados: o grupo experimento apresentou maior acerto (p<0,05) na avaliação do tamanho, consistência, mobilidade e coalescência dos linfonodos na fase final quando comparado ao controle; ainda, apresentou mais chances de avaliar corretamente a consistência (OR 45,26; IC 95% 7,74 - 264,54; p<0,0001), mobilidade (OR 55,95; IC 95% 12,45 - 251,60; p<0,0001) e tamanho (OR 25,64; IC 95% 3,92 - 160,62; p=0,0002) dos linfonodos. Conclusão: os resultados reforçam a contribuição do módulo instrucional para o aumento do conhecimento de estudantes de enfermagem sobre a avaliação de linfonodos.

Objetivo: evaluar la contribución de un módulo instruccional a la identificación del número y características de ganglios linfáticos por estudiantes de pregrado de enfermería. Método: estudio experimental, aleatorizado, controlado y enmascarado mediante intervención de un módulo instruccional. Los 68 estudiantes que integraron el grupo control o el grupo experimental realizaron en las fases inicial y final la palpación de los ganglios linfáticos en prototipo, tras el registro libre de las características y número de estas estructuras. El módulo instruccional (prototipo de palpación y un instrumento-guía de registro) se aplicó al grupo de Experimental. Para el análisis, se utilizó estadística descriptiva y regresión lineal mixta. Resultados: el grupo Experimental mostró mayor acierto (p<0,05) en la evaluación del tamaño, consistencia, movilidad y coalescencia de los ganglios linfáticos en la fase final en comparación con el control; aun así, presentó más probabilidad de evaluar correctamente la consistencia (OR 45,26; IC del 95% 7,74 - 264,54; p<0,0001), la movilidad (OR 55,95; IC del 95% 12,45 - 251, 60; p<0,0001) y tamaño (OR 25,64; IC 95% 3,92 - 160,62; p=0,0002) de los ganglios linfáticos. Conclusión: los resultados refuerzan el aporte del módulo instruccional para el incremento del conocimiento de los estudiantes de enfermería sobre la evaluación de ganglios linfáticos.

Treatment of male genital lymphedema with non-elastic fabric.

Lymphedema is a specific type of edema stemming from a failure in the formation or drainage of lymph. This condition can be congenital or acquired. The clinical treatment of genital lymphedema involves compression mechanisms of the penis. In acquired cases, the individual is born with the lymphatic system intact, but this system is damaged at some point in life, which can lead to lymphatic insufficiency and the development of edema. The non-elastic material for the penis is grosgrain that enable the adjustment to the proper pressure. This report describes a case series of penile lymphedema treated with compression mechanism. Thirteen consecutive patients with penoscrotal lymphedema aged 22 to 56 years (mean: 42.3 years) were treated. Inclusion criteria were patients with primary and secondary penoscrotal lymphedema. Volume larger than three times the normal size of the scrotum was excluded. Reductions in edema occurred in the penis in all patients. Such reductions varied in accordance with the adherence of the patients to the use and duration of compression. The patients used the compression device at times that best fit their schedules. An interesting aspect was the fact that the patients reported the possibility of leaving the penis the size they wished-neither very small nor very large-for sexual activity. All were able to control the size of the edema within the standards they considered acceptable.

Cancer treatment in the lymphatic system: A prospective targeting employing nanostructured systems.

Cancer related to lymphangiogenesis has gained a great deal of attention in recent decades ever since specific markers of this intriguing system were discovered. Unlike the blood system, the lymphatic system has unique features that can advance cancer in future metastasis, or, conversely, can provide an opportunity to prevent or treat this disease that affects people worldwide. The aim of this review is to show the recent research of cancer treatment associated with the lymphatic system, considered one of the main gateways for disseminating metastatic cells to distant organs. Nanostructured systems based on theranostics and immunotherapies can offer several options for this complex disease. Precision targeting and accumulation of nanomaterials into the tumor sites and their elimination, or targeting the specific immune defense cells to promote optimal regression of cancer cells are highlighted in this paper. Moreover, therapies based on nanostructured systems through lymphatic systems may reduce the side effects and toxicity, avoid first pass hepatic metabolism, and improve patient recovery. We emphasize the general understanding of the association between the immune and lymphatic systems, their interaction with tumor cells, the mechanisms involved and the recent developments in several nanotechnology treatments related to this disease.

Neotropical Rattlesnake (Crotalus simus) Venom Pharmacokinetics in Lymph and Blood Using an Ovine Model.

The most abundant protein families in viper venoms are Snake Venom Metalloproteases (SVMPs), Snake Venom Serine Proteases (SVSPs) and Phospholipases (PLA2s). These are primarily responsible for the pathophysiology caused by the bite of pit-vipers; however, there are few studies that analyze the pharmacokinetics (PK) of whole venom (WV) and its protein families. We studied the pathophysiology, PK profile and differential absorption of representative toxins from venom of Neotropical Rattlesnake (Crotalus simus) in a large animal model (ovine). Toxins studied included crotoxin (the main lethal component), which causes moderate to severe neurotoxicity; SVSPs, which deplete fibrinogen; and SVMPs, which cause local tissue damage and local and systemic hemorrhage. We found that Whole Venom (WV) was highly bioavailable (86%) 60 h following intramuscular (IM) injection, and extrapolation suggests that bioavailability may be as high as 92%. PK profiles of individual toxins were consistent with their physicochemical properties and expected clinical effects. Lymph cannulated animals absorbed 1.9% of WV through lymph during the first 12 h. Crotoxin was minimally detectable in serum after intravenous (IV) injection; however, following IM injection it was detected in lymph but not in blood. This suggests that crotoxin is quickly released from the blood toward its tissue targets.

Morphological aspects of the superficial lymph nodes of Myrmecophaga tridactyla

Background: The giant anteater is a Xenarthra of the Myrmecophagidae family. It is classified in Brazil as vulnerablespecie, however, in Rio de Janeiro and Rio Grande do Sul it is probably extinct. In an attempt to contribute to the preservation of the species, many injured animals are referred for treatment and rehabilitation, but the lack of information aboutmorphology may hinder a more efficient clinical-surgical approach. The knowledge on the topography, dimensions andmorphology of lymph nodes of a given species is essential for medical practice. The aim of this study was to identify anddescribe the general morphology of the superficial lymph nodes of Myrmecophaga tridactyla.Materials, Methods & Results: Ten cadavers of adult Myrmecophaga tridactyla were used in this study. They were fixedand preserved with 10% formaldehyde solution and dissected throughout their length to locate their superficial lymphnodes. Lymph nodes of each center were removed for mesoscopic analysis. Measurements of width, length and thicknesswere obtained by a digital caliper. The superficial lymph nodes observed in the head were the mandibular and the intermandibular, while in the neck were identified superficial cervical and deep cervical lymph nodes. In the thoracic limbs,the axillary and the axillary accessory lymph nodes were present. In the pelvic limbs just one lymph node, the femoral,was observed, located in the thick subcutaneous fascia of the medial surface of the thigh. The main anatomical differencesfound in the lymph nodes of M. tridactyla are the absence of parotid, popliteal and subiliac lymph nodes and the presenceof intermandibular lymph nodes and the developed femoral lymph nodes, which are unique in the pelvic limbs of this species. Moreover, some superficial lymph nodes were formed by several small lymph nodes, forming clusters, as observedin the proper and accessory axillary and femoral...(AU)