Appendiceal Mucinous Neoplasms: From Clinic to Pathology and Prognosis.

Appendiceal mucinous neoplasms have been classified differently over time causing confusion when comparing results between working groups in this field and establishing a prognosis of the disease. A historical perspective of the different classification systems of these tumors is essential for the understanding of the evolution of concepts and histopathological definitions that have led up to the present moment. We carried out a systematic review of the pathological classifications of appendiceal mucinous tumors and how they have included the new criteria resulting from clinical and pathological research. The latest classifications by PSOGI and AJCC 8th edition Cancer Staging have made a great effort to incorporate the new pathological descriptions and develop prognostic groups. The introduction of these new classification systems has posed the challenge of verifying how they adapt to our casuistry and which one defines best the prognosis of our patients. We reclassified our series of patients treated for mucinous appendiceal tumors with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy following the PSOGI and the AJCC 8th edition criteria and concluded that both classifications correspond well with the OS and DFS of these patients, with some advantage relative to the PSOGI classification due to a better histopathological description of the different groups.

Chemoenzymatic Synthesis of Glycopeptides to Explore the Role of Mucin†1 Glycosylation in Cell Adhesion.

Post-translational modifications affect protein biology under physiological and pathological conditions. Efficient methods for the preparation of peptides and proteins carrying defined, homogeneous modifications are fundamental tools for investigating these functions. In the case of mucin 1 (MUC1), an altered glycosylation pattern is observed in carcinogenesis. To better understand the role of MUC1 glycosylation in the interactions and adhesion of cancer cells, we prepared a panel of homogeneously O-glycosylated MUC1 peptides by using a quantitative chemoenzymatic approach. Cell-adhesion experiments with MCF-7 cancer cells on surfaces carrying up to six differently glycosylated MUC1 peptides demonstrated that different glycans have a significant impact on adhesion. This finding suggests a distinct role for MUC1 glycosylation patterns in cancer cell migration and/or invasion. To decipher the molecular mechanism for the observed adhesion, we investigated the conformation of the glycosylated MUC1 peptides by NMR spectroscopy. These experiments revealed only minor differences in peptide structure, therefore clearly relating the adhesion behaviour to the type and number of glycans linked to MUC1.

Diagnóstico fortuito de neoplasia mucinosa de apéndice establecido durante la cesárea / Incidental diagnosis of mucinous neoplasm of appendix established during caesarean section

Resumen ANTECEDENTES: Los tumores del apéndice son bastante excepcionales y el adenocarcinoma mucinoso es el más frecuente de estos tumores. Esta patología es aún más infrecuente en pacientes embarazadas. CASO CLÍNICO: Paciente de 43 años, en curso de las 38.1 semanas del primer embarazo. Antecedentes: diabetes gestacional y obesidad mórbida. Se hospitalizó para practicarle la cesárea de urgencia, indicada por restricción del crecimiento intrauterino, sin posibilidad de una conducta expectante. En la ecografía de control prenatal del primer trimestre se describió la existencia de una masa quística, tabicada, de aproximadamente 12 x 12 cm. En la resonancia magnética nuclear de abdomen se encontró una lesión quística en el flanco derecho, de probable origen de masa anexial derecha de 12 x 9 cm. El estudio histopatológico reportó el hallazgo de una neoplasia mucinosa de bajo grado, asociada con extravasación extramural de mucina del apéndice cecal y un pseudomixoma peritoneal. CONCLUSIÓN: El hallazgo de una neoplasia mucinosa del apéndice en una paciente embarazada es sumamente raro. Su diagnóstico supone un reto, sobre todo en quienes no tienen síntomas. Aunque hay padecimientos más frecuentes en las mujeres, como los tumores de ovario o la apendicitis, vale la pena tener en cuenta este cuadro clínico en futuras pacientes. Se requiere mayor investigación de esta neoplasia en embarazadas para optimizar los métodos diagnósticos y poder tratarla de manera oportuna y evitar dañar al feto o la madre.

Abstract BACKGROUND: Tumours of the appendix are quite rare, with mucinous adenocarcinoma being the most frequent of these tumours. This pathology is even rarer in pregnant patients. CLINICAL CASE: 43-year-old patient, in the course of 38.1 weeks of her first pregnancy. History: gestational diabetes and morbid obesity. She was hospitalised for emergency caesarean section, indicated for intrauterine growth restriction, with no possibility of expectant management. The first trimester prenatal ultrasound scan showed a cystic mass, septate, measuring approximately 12 x 12 cm. Magnetic resonance imaging of the abdomen revealed a cystic lesion in the right flank, probably caused by a right adnexal mass measuring 12 x 9 cm. Histopathological study reported the finding of a low-grade mucinous neoplasm associated with extramural extravasation of mucin from the cecal appendix and a peritoneal pseudomyxoma. CONCLUSION: The finding of a mucinous neoplasm of the appendix in a pregnant patient is extremely rare. It is challenging to diagnose, especially in those without symptoms. Although there are more common conditions in women, such as ovarian tumours or appendicitis, this condition is worth considering in future patients. Further investigation of this neoplasm in pregnant women is needed to optimise diagnostic methods to treat it in a timely manner and to avoid harm to the foetus or the mother.

Mucina salival en pacientes obesos en relación al tratamiento de la enfermedad periodontal / Salivary mucin in obese patients in relation to the treatment of periodontal disease

Introducción: La mucina salival (Ms) modula otras proteínas salivales que participan en múltiples funciones fisiológicas de la cavidad oral. Los niveles de Ms pueden proporcionar información sobre el estado de inflamación de los tejidos periodontales. Por tanto, el objetivo del presente estudio fue evaluar los niveles Ms en pacientes obesos y no obesos, antes y después del tratamiento periodontal. Material y métodos: Un total de 60 pacientes fueron distribuidos en seis grupos, de acuerdo al índice de masa corporal (IMC) y la gravedad de la enfermedad periodontal (EP). Valores del IMC superiores a 27 correspondían a obesidad. La EP en el momento del diagnóstico se designó como leve, moderada o severa. Se recolectaron muestras de saliva completa, antes (MU-A) y después (MU-D) del tratamiento periodontal. Se evaluaron los niveles de Ms utilizando el método de Azul Alcian. Los resultados se analizaron con el Software InfoStat, mediante estadística descriptiva e inferencial. Resultados: Los valores de MU-A fueron superiores a los contenidos de MU-D (p < 0.0001). Las variaciones entre los pacientes no obesos y obesos fueron mínimas. A medida que aumentó el nivel de la EP, las variables MU-A y MU-D mostraron una disminución progresiva (p = 0.0032). Conclusiones: El nivel de Ms fue mayor en la saliva de los pacientes con EP no tratada. Ms se puede utilizar como marcador inflamatorio para la detección de EP (AU)

Introduction: Salivary mucin (sM) modulates other salivary proteins that participate in multiple physiological functions of the oral cavity. sM levels can provide information on the state of inflammation of the periodontium. Therefore, the objective of the present study was to evaluate sM levels in obese and non-obese patients, before and after periodontal treatment. Material and methods: A total of 60 patients were distributed into six groups, according to the body mass index (BMI) and the severity of the periodontal disease (PD). BMI values higher than 27 corresponded to obesity. PD at the time of diagnosis was designated as mild, moderate, or severe. Complete saliva samples were collected before (MU-B) and after (MU-A) the periodontal treatment. sM levels were evaluated using the Alcian Blue method. The results were analyzed with the InfoStat Software, using descriptive and inferential statistics. Results: MU-B values were higher than MU-A contents (p < 0.0001). Variations between non-obese and obese patients were minimal. As the level of PD increased, the variables MU-A and MU-D showed a progressive decrease (p = 0.0032). Conclusions: The level of sM was higher in the saliva of patients with untreated PD. sM can be used as an inflammatory marker for the detection of PD (AU)

Scleredema Diabeticorum / Escleredema Diabeticorum Scleredema Diabeticorum

Abstract Scleredema diabeticorum is one of the skin disorders associated with diabetes mellitus, characterized by thickening of the deep layers of the dermis, with excessive mucin and collagen deposition, clinically evidenced in hardening of the skin, especially in the upper half of the body. We describe the clinical case of an adult male diabetic who was seen for an indurated cervical lesion which was subsequently diagnosed histopathologically as scleredema diabeticorum. The interest in this case lies in the low prevalence of the condition and its association with poor metabolic control of diabetes. (Acta Med Colomb 2021; 46. DOI:https://doi.org/10.36104/amc.2021.1888).

Resumen Dentro de los trastornos cutáneos asociados a la diabetes mellitus, se describe el escleredema diabeticorum el cual se caracteriza por un engrosamiento de las capas profundas de la dermis con depósito excesivo de mucina y colágeno, que produce clínicamente endurecimiento de la piel, principalmente en la mitad superior del cuerpo. Se describe un caso clínico correspondiente a un hombre adulto diabético que consultó por la aparición de una lesión indurada en la región cervical con posterior diagnóstico histopatológico de escleroderma diabeticorum. El interés radica en la baja prevalencia de la condición y su asociación al pobre control metabólico de la diabetes. (Acta Med Colomb 2021; 46. DOI:https://doi.org/10.36104/amc.2021.1888).

Role of Soluble T-Cell Immunoglobulin Mucin Domain-3 in Differentiating Nontuberculous Mycobacterial Lung Disease from Pulmonary Colonization.

BACKGROUND: Differentiating between nontuberculous mycobacterial lung disease (NTM-LD) and pulmonary NTM colonization (NTM-Col) is difficult. Compared with healthy controls, patients with NTM-LD generally present immune tolerance along with increased expressions of T-cell immunoglobulin mucin domain-3 (TIM-3) and programmed cell death-1 (PD-1) on T lymphocytes. However, the role of soluble TIM-3 (sTIM-3) and soluble PD-1 (sPD-1) in differentiating NTM-LD from NTM colonization (NTM-Col) remains unclear. METHODS: Patients with NTM-positive respiratory samples and controls were enrolled from 2016 to 2019. Patients were classified into NTM-Col and NTM-LD groups. Levels of sTIM-3, sPD-1, soluble PD-ligand-1 (sPD-L1), and TIM-3 expression were measured. Factors associated with NTM-LD were analyzed by logistical regression. RESULTS: TIM-3 expression on CD4+ and CD8+ T lymphocytes were highest in NTM-LD group, followed by NTM-Col, and control (P=.017 and P=.011 for trend). sTIM-3 elevated in the NTM-Col group compared with the NTM-LD and control groups (856.3±518.7 vs. 595.3±352.6pg/mL, P=.009; vs. 437.0±267.4pg/mL, P<.001). Levels of sPD-1 and sPD-L1 were similar among groups. Among the 79 NTM-positive patients, sTIM-3 was associated with NTM-LD (100-pg/mL increase, adjusted odds ratio (aOR) 0.658 [95% CI, 0.502-0.864], P=.003). Patients with ≥2 risk factors (sTIM-3≤530pg/mL, BMI≤22.5, and radiographic score ≥5) were 13 times more likely to exhibit NTM-LD than those without (aOR 13.234 [2.983-58.709], P=.001). CONCLUSIONS: sTIM-3 was an independent factor for differentiating NTM-LD from NTM-Col, suggesting the immunologic role of sTIM-3 in NTM-LD pathogenesis. By assessing sTIM-3 levels and other risk factors, physicians may be able to identify NTM-LD cases in a simplified manner.

Mucina y Enfermedad Periodontal / Mucin and periodontal disease

La enfermedad periodontal (EP) es una patología que afecta principalmente los tejidos que rodean a la pieza dentaria (PD) y se caracteriza, en la mayoría de los casos, por una exposición bacteriana que favorece una respuesta destructiva e inflamatoria del huésped, que conduce a la pérdida de inserción periodontal de la PD, provocando una marcada reabsorción ósea y la posible pérdida de las PD. El diagnóstico de EP implica evaluaciones clínicas y radiográficas, en la actualidad se están realizando diversas investigaciones para evaluar posibles compuestos en los fluidos orales a través de lo cual puede ser posible evaluar la presencia y gravedad de estas enfermedades, como así también el riesgo en los pacientes. Hay evidencias de la interacción de macromoléculas salivales, como las mucinas, con microorganismos específicos. De esta manera las mucinas, junto con otros productos de la saliva, ayudan a modular tanto el número como el tipo de proliferación de ciertos organismos y provocar la disminución de otros. La revisión de la literatura actual concluye que las mucinas salivales pueden servir como un parámetro bioquímico de la inflamación del periodonto (AU)

Periodontal disease (PD) is a pathology that mainly affects the tissues surrounding the tooth (PD) and is characterized, in most cases, by a bacterial exposure that favors a destructive and inflammatory response of the host, which leads to the loss of periodontal insertion of the PD, causing a marked bone resorption and the possible loss of the PD. The diagnosis of PD involves clinical and radiographic evaluations, at present several investigations are being carried out to evaluate possible compounds in oral fluids through which it may be possible to evaluate the presence and severity of these diseases, as well as the risk in patients. There is evidence of the interaction of salivary macromolecules, such as mucins, with specific microorganisms. In this way, mucins, together with other saliva products, help modulate both the number and type of proliferation of certain organisms and cause the decrease of others. The review of the current literature concludes that salivary mucins can serve as a biochemical parameter of inflammation of the periodontium (AU)

Concentración de mucina salival en pacientes con enfermedad periodontal / Concentração de mucina salivar em pacientes com doença periodontal / Salivary mucin concentration in patients with periodontal disease

Resumen El objetivo de este trabajo fue estudiar la relación entre la concentración de mucina salival y la enfermedad periodontal. La muestra se dividió en tres grupos de 20 individuos cada uno: Grupo 1 sin enfermedad periodontal; Grupo 2 con gingivitis; y Grupo 3 con periodontitis. En todas las muestras salivales se confirmó la presencia de mucina, el Grupo 1 presentó un valor promedio de 1,27 mg/ml. En el Grupo 2 se registró un promedio de 1,93 mg/ml. En el Grupo 3 se observó un promedio de 3,01 mg/ml. El Análisis de la Variancia y posterior prueba de F (F = 25,01, p < 0,0001) confirman diferencias significativas en los contenidos de mucina entre grupos. El aumento de la concentración de mucina salival en pacientes periodontales podría representar un marcador químico de utilidad como coadyuvante en el diagnóstico clínico de esta enfermedad.

Resumo O objetivo deste trabalho foi estudar a relação entre a concentração de mucina salivar e a doença periodontal. A amostra foi dividida em três grupos de 20 indivíduos cada: Grupo 1 sem doença periodontal; Grupo 2 com gengivite; e Grupo 3 com periodontite. Em todas as amostras salivares foi confirmada a presença de mucina, o Grupo 1 apresentou valor médio de 1,27 mg / ml. No Grupo 2, foi registrada uma média de 1,93 mg / ml. No Grupo 3 foi observada uma média de 3,01 mg / ml. A Análise de Variância e o teste F subsequente (F = 25,01, p <0,0001) confirmam diferenças significativas nos conteúdos de mucina entre os grupos. O aumento da concentração de mucina salivar em pacientes periodontais pode representar um marcador químico útil como adjuvante no diagnóstico clínico desta doença.

Abstract This work aimed to study the relationship between salivary mucin concentration and periodontal disease. The sample was divided into three groups of 20 individuals each: Group 1 with no periodontal disease, Group 2 with gingivitis, and Group 3 with periodontitis. Mucin was detected in all the saliva samples. Group 1 had an average value of 1.27 mg/ml. Group 2 had an average value of 1.93 mg/ml. Group 3 had an average value of 3.01 mg/ml. The analysis of variance and subsequent F test (F = 25.01, p < 0.0001) confirmed significant differences in mucin content between the groups. Increased salivary mucin concentration in periodontal patients could be a useful chemical marker for the clinical diagnosis of periodontal disease.

Papulonodular mucinosis in the primary onset of juvenile systemic lupus erythematosus: An unusual association / Mucinosis papulonodular en el inicio de lupus eritematoso sistêmico juvenil: asociación inusual

ABSTRACT Cutaneous mucinosis is a group of conditions characterized by the abnormal deposition of mucin in the skin. They can be primary, which in turn can be inflammatory-degenerative, and hamartomatous-neoplastic; or secondary. Papulonodular mucinosis is part of the group of dermal inflammatory-degenerative primary mucinosis. Its association with autoimmune connective tissue diseases has been described, especially with systemic lupus erythematosus, but it is considered an unusual manifestation of this disease. The clinical case is presented of an 11 year-old girl who, at the onset of systemic lupus erythematosus, presented with skin lesions for which the histopathological diagnosis corresponded to mucinosis.

RESUMEN Las mucinosis cutáneas son un grupo de condiciones caracterizadas por el depósito anormal de mucina en la piel. Pueden ser primarias, que a su vez pueden ser inflamatorias-degenerativas (dérmicas o foliculares) y hamartomatosas-neoplásicas; o secundarias. La mucinosis papulonodular forma parte de las mucinosis primarias inflamatorias-degenerativas dérmicas. Se ha descrito su asociación con enfermedades autoinmunes del tejido conectivo, especialmente con el lupus eritematoso sistémico, pero se considera una manifestación inusual de esta enfermedad. Se presenta el caso clínico de una niña de 11 años, quien al inicio del lupus eritematoso sistémico presentaba lesiones en la piel cuyo diagnóstico histopatológico correspondió a mucinosis.

MUC1 expression in colorectal carcinoma: Clinicopathological correlation and prognostic significance.

INTRODUCTION: MUC1 overexpression has been linked to cancer development and has been associated with a higher stage at diagnosis and presence of lymph node or distant metastases. However, its prognostic significance is still unclear. We aimed to evaluate the relationship between MUC1 expression and prognosis of colorectal carcinoma. MATERIALS AND METHODS: Immunohistochemical expression of MUC1 in 96 colorectal carcinomas with analysis of potential prognostic influence. RESULTS: 55.2% of patients were women and the mean age was 65.9 years. Tumors were more frequently located in rectum or sigmoid colon (60.4% and 21.9%). Most tumors were T3 (60.3%). 36.9% of patients showed lymph node metastases and 30.2% showed distant metastasis at the time of diagnosis. MUC1 was intensely positive in 46% and negative in 37.9% of tumors. Overall, 61% of patients recurred and 40.4% died during follow-up. 58.5% of tumors of surviving patients were intensely positive for MUC1 and 29.5% were negative, as compared with 28.5% (intense positivity) and 51.4% (negativity) in the group of patients who died (p=0.022). 65% of tumors of patients without recurrences showed intense positivity for MUC1 and 23% of them were negative as compared with 33.9% (intense positivity) and 47% (negativity) in the group of patients who recurred (p=0.019). CONCLUSIONS: Loss of MUC1 expression was more frequent in cases with disease recurrence or death, as compared with patients with stable disease, in whom intense positivity was more frequently seen. These findings disagree with the majority of previous studies, indicating the need for further investigation.

Evaluation of enemas containing sucralfate in tissue content of muc-2 protein in experimental model of diversion colitis / Avaliação de enemas com sucralfato no conteúdo tecidual da proteina muc-2 em colite de exclusão experimental

ABSTRACT Background: The effects of topical application of sucralfate (SCF) on the tissue content of MUC-2 protein have not yet been evaluated in experimental models of diversion colitis. Aim: To measure the tissue content of MUC-2 protein in the colonic mucosa diverted from fecal stream submitted to the SCF intervention. Methods: Thirty-six rats underwent derivation of intestinal transit through proximal colostomy and distal mucous fistula. The animals were divided into three groups which were submitted application of enemas with saline, SCF 1 g/kg/day and SCF 2 g/kg/day. Each group was divided into two subgroups, according to euthanasia was done after two or four weeks. The colitis diagnosis was established by histopathological study and the inflammatory intensity was evaluated by previously validated scale. The MUC-2 protein was identified by immunohistochemistry and the tissue content was measured computerized morphometry). Results: The application of enemas with SCF in the concentration of 2 g/kg/day reduced inflammatory score of the segments that were diverted from fecal stream. The content of MUC-2 in diverted colon of the animals submitted to the intervention with SCF, independently of intervention period and the used concentration, was significantly greater than animals submitted to the application of enemas containing saline (p< 0.01). The content of MUC-2 after the intervention with SCF in the concentration of 2 g/kg/day was significantly higher when compared to the animals submitted to the application containing SCF at concentration of 1.0 g/kg/day (p<0.01). The tissue content of MUC-2 reached the highest values after intervention with SCF in the concentration of 2 g/kg/day for four weeks (p<0.01). Conclusion: The preventive application of enemas containing SCF reduces the inflammatory score and avoids the reduction of tissue content of MUC-2, suggesting that the substance is a valid therapeutic strategy to preserve the mucus layer that covers the intestinal epithelium.

RESUMO Racional: Os efeitos da aplicação tópica de sucralfato (SCF) no conteúdo tecidual da proteína mucina-2 (MUC-2) ainda não foram avaliados em modelos experimentais de colite de exclusão. Objetivo: Mensurar o conteúdo tecidual da proteína MUC-2 na mucosa cólica sem trânsito intestinal submetida à intervenção com SCF. Método: Trinta e seis ratos foram submetidos à derivação intestinal por colostomia proximal terminal e fístula mucosa distal. Foram divididos em três grupos segundo recebessem clisteres contendo solução fisiológica (SF), SCF 1 g/kg/dia e SCF 2 g/kg/dia. Cada grupo foi dividido em dois subgrupos, segundo a eutanásia ser realizada após duas ou quatro semanas. O diagnóstico de colite foi estabelecido por estudo histopatológico e a intensidade inflamatória foi avaliada por escala validada. A expressão tecidual da MUC-2 foi identificada por imunoistoquímica e seu conteúdo mensurado por morfometria computadorizada. Resultados: A aplicação de clisteres com SCF na concentração de 2 g/kg/dia reduziu a intensidade inflamatória no cólon sem trânsito fecal. O conteúdo tecidual de MUC-2 no cólon sem trânsito dos animais submetidos à intervenção com SCF, independente do tempo de intervenção e da concentração utilizada, foi maior quando comparado aos animais tratados com SF (p<0,01). O conteúdo de MUC-2 após a intervenção com SCF na concentração de 2 g/kg/dia foi maior quando comparado aos animais submetidos à intervenção com concentração menor (p<0,01). O conteúdo de MUC-2 foi maior após intervenção com SCF na concentração de 2 g/kg/dia por quatro semanas (p<0,01). Conclusão: A aplicação preventiva de clisteres com SCF reduz o grau de inflamação e preserva o conteúdo tecidual de MUC-2, em segmentos desprovidos de trânsito intestinal, mostrando-se uma estratégia terapêutica válida para preservar a camada de muco que recobre o epitélio intestinal.

[retracted article]: evaluation of enemas containing sucralfate in tissue content of muc-2 protein in experimental model of diversion colitis / [artigo retratado]: avaliação de enemas com sucralfato no conteúdo tecidual da proteina muc-2 em colite de exclusão experimental

ABSTRACT Background: The effects of topical application of sucralfate (SCF) on the tissue content of MUC-2 protein have not yet been evaluated in experimental models of diversion colitis. Aim: To measure the tissue content of MUC-2 protein in the colonic mucosa diverted from fecal stream submitted to the SCF intervention. Methods: Thirty-six rats underwent derivation of intestinal transit through proximal colostomy and distal mucous fistula. The animals were divided into three groups which were submitted application of enemas with saline, SCF 1 g/kg/day and SCF 2 g/kg/day. Each group was divided into two subgroups, according to euthanasia was done after two or four weeks. The colitis diagnosis was established by histopathological study and the inflammatory intensity was evaluated by previously validated scale. The MUC-2 protein was identified by immunohistochemistry and the tissue content was measured computerized morphometry). Results: The application of enemas with SCF in the concentration of 2 g/kg/day reduced inflammatory score of the segments that were diverted from fecal stream. The content of MUC-2 in diverted colon of the animals submitted to the intervention with SCF, independently of intervention period and the used concentration, was significantly greater than animals submitted to the application of enemas containing saline (p< 0.01). The content of MUC-2 after the intervention with SCF in the concentration of 2 g/kg/day was significantly higher when compared to the animals submitted to the application containing SCF at concentration of 1.0 g/kg/day (p<0.01). The tissue content of MUC-2 reached the highest values after intervention with SCF in the concentration of 2 g/kg/day for four weeks (p<0.01). Conclusion: The preventive application of enemas containing SCF reduces the inflammatory score and avoids the reduction of tissue content of MUC-2, suggesting that the substance is a valid therapeutic strategy to preserve the mucus layer that covers the intestinal epithelium.

RESUMO Racional: Os efeitos da aplicação tópica de sucralfato (SCF) no conteúdo tecidual da proteína mucina-2 (MUC-2) ainda não foram avaliados em modelos experimentais de colite de exclusão. Objetivo: Mensurar o conteúdo tecidual da proteína MUC-2 na mucosa cólica sem trânsito intestinal submetida à intervenção com SCF. Método: Trinta e seis ratos foram submetidos à derivação intestinal por colostomia proximal terminal e fístula mucosa distal. Foram divididos em três grupos segundo recebessem clisteres contendo solução fisiológica (SF), SCF 1 g/kg/dia e SCF 2 g/kg/dia. Cada grupo foi dividido em dois subgrupos, segundo a eutanásia ser realizada após duas ou quatro semanas. O diagnóstico de colite foi estabelecido por estudo histopatológico e a intensidade inflamatória foi avaliada por escala validada. A expressão tecidual da MUC-2 foi identificada por imunoistoquímica e seu conteúdo mensurado por morfometria computadorizada. Resultados: A aplicação de clisteres com SCF na concentração de 2 g/kg/dia reduziu a intensidade inflamatória no cólon sem trânsito fecal. O conteúdo tecidual de MUC-2 no cólon sem trânsito dos animais submetidos à intervenção com SCF, independente do tempo de intervenção e da concentração utilizada, foi maior quando comparado aos animais tratados com SF (p<0,01). O conteúdo de MUC-2 após a intervenção com SCF na concentração de 2 g/kg/dia foi maior quando comparado aos animais submetidos à intervenção com concentração menor (p<0,01). O conteúdo de MUC-2 foi maior após intervenção com SCF na concentração de 2 g/kg/dia por quatro semanas (p<0,01). Conclusão: A aplicação preventiva de clisteres com SCF reduz o grau de inflamação e preserva o conteúdo tecidual de MUC-2, em segmentos desprovidos de trânsito intestinal, mostrando-se uma estratégia terapêutica válida para preservar a camada de muco que recobre o epitélio intestinal.

A review on autosomal dominant tubulointerstitial kidney disease. / Revisión de la nefropatía tubulointersticial autosómica dominante.

In recent years there has been a reclassification of hereditary tubulointerstitial renal diseases. The old concepts of nephronoptisis or medullary cystic disease have been reordered based on the discovery of new genes. The 2015 KDIGO guidelines proposed a unification of terminology, diagnostic criteria and monitoring. So far 4genes causing autosomal dominant tubulointerstitial kidney disease have been described: MUC1, UMOD, HNF1B and REN. Although the mutation in each of them causes distinctive features in how they present, all have in common the progressive tubulointerstitial damage and renal fibrosis. In this article, we present a review of the guidelines and the literature, and some practical recommendations for dealing with this disease.

Evaluation of enemas containing sucralfate in tissue content of muc-2 protein in experimental model of diversion colitis / Avaliação de enemas com sucralfato no conteúdo tecidual da proteina muc-2 em colite de exclusão experimental

ABSTRACT Background: The effects of topical application of sucralfate (SCF) on the tissue content of MUC-2 protein have not yet been evaluated in experimental models of diversion colitis. Aim: To measure the tissue content of MUC-2 protein in the colonic mucosa diverted from fecal stream submitted to the SCF intervention. Methods: Thirty-six rats underwent derivation of intestinal transit through proximal colostomy and distal mucous fistula. The animals were divided into three groups which were submitted application of enemas with saline, SCF 1 g/kg/day and SCF 2 g/kg/day. Each group was divided into two subgroups, according to euthanasia was done after two or four weeks. The colitis diagnosis was established by histopathological study and the inflammatory intensity was evaluated by previously validated scale. The MUC-2 protein was identified by immunohistochemistry and the tissue content was measured computerized morphometry). Results: The application of enemas with SCF in the concentration of 2 g/kg/day reduced inflammatory score of the segments that were diverted from fecal stream. The content of MUC-2 in diverted colon of the animals submitted to the intervention with SCF, independently of intervention period and the used concentration, was significantly greater than animals submitted to the application of enemas containing saline (p< 0.01). The content of MUC-2 after the intervention with SCF in the concentration of 2 g/kg/day was significantly higher when compared to the animals submitted to the application containing SCF at concentration of 1.0 g/kg/day (p<0.01). The tissue content of MUC-2 reached the highest values after intervention with SCF in the concentration of 2 g/kg/day for four weeks (p<0.01). Conclusion: The preventive application of enemas containing SCF reduces the inflammatory score and avoids the reduction of tissue content of MUC-2, suggesting that the substance is a valid therapeutic strategy to preserve the mucus layer that covers the intestinal epithelium.

RESUMO Racional: Os efeitos da aplicação tópica de sucralfato (SCF) no conteúdo tecidual da proteína mucina-2 (MUC-2) ainda não foram avaliados em modelos experimentais de colite de exclusão. Objetivo: Mensurar o conteúdo tecidual da proteína MUC-2 na mucosa cólica sem trânsito intestinal submetida à intervenção com SCF. Método : Trinta e seis ratos foram submetidos à derivação intestinal por colostomia proximal terminal e fístula mucosa distal. Foram divididos em três grupos segundo recebessem clisteres contendo solução fisiológica (SF), SCF 1 g/kg/dia e SCF 2 g/kg/dia. Cada grupo foi dividido em dois subgrupos, segundo a eutanásia ser realizada após duas ou quatro semanas. O diagnóstico de colite foi estabelecido por estudo histopatológico e a intensidade inflamatória foi avaliada por escala validada. A expressão tecidual da MUC-2 foi identificada por imunoistoquímica e seu conteúdo mensurado por morfometria computadorizada. Resultados: A aplicação de clisteres com SCF na concentração de 2 g/kg/dia reduziu a intensidade inflamatória no cólon sem trânsito fecal. O conteúdo tecidual de MUC-2 no cólon sem trânsito dos animais submetidos à intervenção com SCF, independente do tempo de intervenção e da concentração utilizada, foi maior quando comparado aos animais tratados com SF (p<0,01). O conteúdo de MUC-2 após a intervenção com SCF na concentração de 2 g/kg/dia foi maior quando comparado aos animais submetidos à intervenção com concentração menor (p<0,01). O conteúdo de MUC-2 foi maior após intervenção com SCF na concentração de 2 g/kg/dia por quatro semanas (p<0,01). Conclusão: A aplicação preventiva de clisteres com SCF reduz o grau de inflamação e preserva o conteúdo tecidual de MUC-2, em segmentos desprovidos de trânsito intestinal, mostrando-se uma estratégia terapêutica válida para preservar a camada de muco que recobre o epitélio intestinal.

Polimorfismos de número variable de repeticiones en tándem del intrón 2 de 5-htt y MUC 7 en pacientes venezolanos con asma o EPOC / 5-HTT intron 2 and MUC7 variable number of tandem repeats polymorphisms in a Venezuelan population with asthma or COPD

El asma y la enfermedad pulmonar obstructiva crónica (EPOC) son enfermedades inflamatorias crónicas. En ambas patologías existe broncoconstricción, producción de mediadores inflamatorios, hipersecreción de moco y migración de células inflamatorias. La serotonina tiene propiedades inmunomoduladoras que facilitan la broncoconstricción y su transportador (5-HTT) es el principal determinante de su concentración plasmática. Las mucinas (MUC) son glicoproteínas involucradas en la inmunidad innata local. El objetivo del presente trabajo fue estudiar la asociación entre polimorfismos de número variable de repeticiones en tándem (VNTR) del intrón 2 de 5-HTT (STin2) y MUC7 en pacientes venezolanos con asma o EPOC. El grupo de estudio consistió en 301 individuos (102 asmáticos, 99 EPOC, y 100 controles). No se observaron diferencias en las frecuencias de polimorfismos de MUC7 entre los grupos. Sin embargo, se encontró asociación entre alelos y genotipos de STin2 con presencia de asma o EPOC (p <0,001). El alelo STin2.9 tuvo un odds ratio (OR) de 0,15 (p=0,16) en los pacientes con asma, mientras que en los pacientes con EPOC los genotipos STin2.10/10 y 10/12 presentaron un OR de 0,33 (p=0,002) y 3,64 (p=0,002), respectivamente. Con relación a los haplotipos, el STin2/MUC7 10/10-6/6 se relacionó con riesgo en asma (OR=1,6, p=0,02) y protección en EPOC (OR=0,3, p=0,006) y el 10/12-6/6 (OR=3,7, p=0,002) fue un factor de riesgo para EPOC. En conclusión, en la población venezolana los polimorfismos de STin2 son importantes para definir factor de riesgo de enfermedad y, en consecuencia, el transportador de serotonina es relevante en ambas patologías.

Asthma and Chronic Obstructive Pulmonary Disease (COPD) are chronic inflammatory diseases. Both entities are characterized by bronchoconstriction, production of inflammatory mediators, mucus hypersecretion and inflammatory cell migration. Serotonin has immunomodulatory properties facilitating bronchoconstriction and its plasma concentration is transporter dependent (5-HTT). Mucins are glycoproteins involved in local innate immunity. The aim of this study was to assess the association between the variable number of tandem repeat polymorphisms (VNTR) of intron 2 of the serotonin ransporter (5-HTT) (STin2) and MUC7 in Venezuelan asthmatic or COPD patients. The group consisted of 301 individuals (102 asthmatics, 99 with COPD and 100 controls). There were no differences in the frequencies of MUC7 polymorphisms among the groups. However, there is a significant association between some alleles and genotypes with the presence of asthma or COPD (p <0.001). The STin2.9 allele had an odds ratio (OR) of 0.15 (p=0.16) in patients with asthma, while in patients with COPD, the STin2.10/10 and 10/12 genotypes had 0.33 (p=0,002) and 3.64 (p=0,002) OR, respectively. Regarding haplotypes, the STin2/ MUC7 10/10-6/6 is related to asthma risk (OR = 1.6, p=0.02) and COPD protection (OR=0.3, p=0.006) and 10/12-6/6 (OR=3.7, p=0.002), is a risk factor for COPD. In conclusion, in the Venezuelan population STin2 polymorphisms are important to define disease risk factor and consequently, the serotonin transporter is relevant to both pathologies.

Efeitos da aguardente de cana em glândulas submandibulares de ratos: avaliação da atividade das fosfatases, níveis de mucina e histomorfometria / Effects of cane brandy on submandibular glands of rats: evaluation of the activity of phosphatases, mucin levels and histomorphometry

O presente estudo teve como objetivo investigar em glândulas submandibulares de ratos tratados com aguardente de cana, a morfologia, atividade funcional das fosfatases e níveis de mucina. 24 ratos machos e adultos foram divididos em 4 grupos (n=6) de acordo com o tipo de bebida fornecida, aguardente de cana (39º GL) ou água, e ao tempo de tratamento de 75 ou 105 dias. Após os períodos de tratamento, os animais foram submetidos à cirurgia para remoção das glândulas submandibulares, seguido da eutanásia. As glândulas submandibulares do lado direito foram processadas para análise histomorfométrica (Image J) dos ductos estriados, ductos granulosos e ácinos. As glândulas do lado esquerdo foram pesadas e armazenadas a -80 °C, para avaliação da atividade funcional da fosfatase ácida total (FAT), fosfatase ácida resistente ao tartarato (FART), fosfatase alcalina (FAL) e determinação dos níveis de mucina. Para isso foram feitos ensaios bioquímicos por métodos espectrofotométricos. Os dados quantitativos foram submetidos à análise estatística (p<0,05). Os pesos absolutos e relativos das glândulas submandibulares apresentam-se reduzidos em relação aos controles (p<0,05). Na análise histomorfométrica, observamos que houve relevante redução da área dos ácinos (p<0,05) e redução não significativa dos ductos estriados (p>0,05). Nos ductos granulosos ocorreu aumento não significativo da área (p>0,05). As atividades de FAT e FART se apresentaram expressivamente diminuídas nos grupos experimentais (p<0,05), enquanto a atividade funcional de FAL diminuiu de forma moderada (p>0,05). Houve redução significativa dos níveis de mucina pelo efeito do alcoolismo crônico (p<0,05). A partir desses dados foi possível concluir que o alcoolismo crônico, por uso de aguardente de cana afeta a funcionalidade bioquímica e a morfologia da glândula submandibular(AU)

The present study aimed to investigate submandibular glands of rats treated with cane brandy, morphology, functional activity of phosphatases and levels of mucin. 24 male and adult rats were divided into 4 groups (n = 6) according to the type of beverage provided, cane brandy (39° GL) or water, and treatment time of 75 or 105 days. After the treatment periods, the animals were submitted to surgery to remove the submandibular glands, followed by euthanasia. The submandibular glands on the right side were processed for histomorphometric analysis (Image J) of the striated ducts, granular ducts and acini. The left glands were weighed and stored at -80 °C for evaluation of the functional activity of total acid phosphatase (TAP), tartrate-resistant acid phosphatase (TRAP), alkaline phosphatase (ALP), and determination of mucin levels. For this, biochemical tests were carried out by spectrophotometric methods. Quantitative data were submitted to statistical analysis (p<0.05). The absolute and relative weights of the submandibular glands are reduced in relation to the controls (p<0.05). In the histomorphometric analysis, we observed that there was a significant reduction of the acini area (p<0.05) and a non-significant reduction of the striated ducts (p>0.05). In the granular ducts a not significant increase of the area occurred (p>0.05). The TAP and TRAP activities were significantly decreased in the experimental groups (p<0.05), while the ALP functional activity decreased moderately (p>0.05). There was a significant reduction of mucin levels by the effect of chronic alcoholism (p<0.05). From these data it was possible to conclude that chronic alcoholism due to the use of cane brandy affects the biochemical functionality and morphology of the submandibular gland(AU)

Expresión de mucinas: MUC1, MUC2, MUC5AC, MUC6, HGM y CD10 en carcinomas gástricos y lesiones pre-neoplasicas adyacentes / MUCIN EXPRESSION: MUC1, MUC2, MUC5AC, MUC6, HGM AND CD10 IN GASTRIC CARCINOMAS AND ADJACENT PRE-NEOPLASTIC LESIONS

Introducción: Las mucinas son glicoproteínas y desempeñan funciones biológicas. Diversas anormalidades genéticas y epgenéticas han sido descritas en el cáncer gástrico. El objetivo de la investigación fue observar la inmuno-expresión de mucinas en cánceres difusos e intestinales y las lesiones pre-neoplásicas limítrofes. Métodos: Se evaluaron 18 cánceres difusos (56.3%) y 14 intestinales (43.7%) y las lesiones precursoras adyacentes al cáncer gástrico. Se realizó inmunohistoquímica para los siguientes marcadores: MUC-1, MUC-2, MUC5-AC, MUC-6, HGM y CD10. Resultados: La inmune-expresiones fue: MUC-1 (54.5%), de los cánceres intestinales y (45.5%) de los cánceres difusos. MUC-2 (50%) de los cánceres difusos y (50%) de los cánceres del tipo intestinal. MUC-5AC (39.3%) del tipo difuso (60.7%) del tipo intestinal. HGM (37.5%) del tipo intestinal y (62.5%) del tipo difuso. MUC-6 (57.9%) del tipo difuso (42.1%) los del tipo intestinal. CD10 (55.6%) del tipo intestinal, y (44.4%) en los difusos.En las lesiones pre- cursoras adyacentes al cáncer gástrico la MUC-1 se inmunoexpresa en metaplasia intestinal (9.7%). MUC-2 (83.9%) en metaplasia intestinal. MUC5-AC (90,6%) en foveolas MUC-6 (100%) positiva en glándulas. CD10 (54.8%) positiva en metaplasia intestinal.HGM (75%) en foveolas y el (64.5%) en metaplasia intestinal. MUC-6 (100%) en glándulas profundas y (64,5%) en metaplasia intestinal. Las dis- plasias expresaron MUC-2 y MUC-5AC, en el 80% y 100% respectivamente. Conclusiones: La inmunotipificación del cáncer gástrico permitirá una clasificación más exacta de los tumores asi como la identificación de posibles dianas terapéuticas y su relación con factores genético y epigeneticos.

Introduction: Mucins are glycoproteins and has diverse biological roles. Epi-genetic abnormalities have been described in gastric cancer. The aim of the research was evaluate immunoexpression of mucins in diffuse and intestinal cancers and pre-neoplastic lesions. Methods: We evaluated 18 diffuse cancers (56.3%) and 14 intestinal (43.7%) and adjacent precursor lesions to gastric cancer immunohistochemical markers used was MUC-1, MUC-2-AC MUC5, MUC-6, and CD10 HGM. Results: The immuno-expression was: MUC-1 (54.5%), and intestinal cancers (45.5%) diffuse cancers. MUC-2 (50%) and diffuse cancers (50%) of cancers of the intestinal type. MUC-5AC (39.3%) diffuse type (60.7%) of intestinal type.HGM (37.5%) intestinal type (62.5%) in diffuse type. MUC-6 (57.9%) diffuse type (42.1%) in the intestinal type. CD10 (55.6%) in intestinal type, and (44.4%) in the diffuse type In adjacent precursor lesions to gastric cancer we observed MUC-1 in intestinal metaplasia (9.7%). MUC-2 (83.9%) in intestinal metaplasia. MUC5-AC (90.6%) in foveolasMUC-6 (100%) positive glands. CD10 (54.8%) positive in intestinal.HGM metaplasia(75%) and in foveolae (64.5%) in metaplasia intestinal. MUC-6 (100%) deep glands (64.5%) in metaplasia.intestinal. Dys- plasias expressed MUC-2 and MUC-5AC, 80% and 100% respectively. Conclusions: The gastric cancer immunotyping allow more accurate classification of tumors and the identification of potential therapeutic targets and its relationship with genetic and epigenetic factors.

The Stomach of the Adult African Catfish (Clarias gariepinus, Siluriforme s: Clariidae) in Farm Conditions: A Morphological and Mucin Histochem istry Analysis / El Estómago del Bagre Africano Adulto (Clarias gariepinus, Siluriformes: Clariidae) en Condiciones de Granja: Análisis Morforlógico e Histoquímico por Mucina

The stomach of the farmed African catfish (Clarias gariepinus, Siluriformes: clariidae) was investigated in this study to establish its basic anatomy, as there is scanty information available on the literature. It produced to baseline data for further investigative research, help fish clinicians in pathology and aid nutritionists in feed management. After cropping from a commercial aquaculture, apparently healthy fish were immobilized and euthanized by using chloroform. The samples were dissected and slices of cardiac, fundic and pyloric stomach processed through routine histological procedures. Grossly, the stomach was J-shape. Cranial to the stomach was the oesophagus but no sphincter was seen separating them. Caudally, a pyloric sphincter separated the stomach from the proximal intestine. The stomach contained three regions cardiac, fundic and pyloric. The entire stomach surface was lined by a simple columnar epithelium containing mucin at the apical cytoplasm. Only the cardiac and fundic regions contained gastric glands in the lamina propria, but the glands were more developed in the fundic region. The tunica muscularis contained smooth muscle cells in an inner circular and outer longitudinal orientation. Mucin histochemistry revealed the presence of only neutral mucin in the stomach. The results obtained in this study suggest that the absence of gastric glands in the pylorus may be an adaptation of this species to reduce the quantity of acid entering the proximal intestine; hence it might help the alkaline medium to maximize pancreatic enzyme actions in the proximal intestine. The presence of only neutral mucin in the stomach will act as a buffer to neutralize the high acidic stomach content. Neutral mucins are also associated with transport of macromolecules.

Se efectuó un estudio de tipo histológico e histoquímico con mucina, en el estómago del bagre africano (Clarias gariepinus, Siluriformes: clariidae) cultivado en granja acuícola, para establecer su anatomía básica, debido a la escasa información disponible en la literatura. La investigación generó datos para ulteriores investigaciones, que contribuirán con los ictiopatólogos y ayudarán a los nutricionistas en el manejo alimentario. Después de su cultivo en una granja acuícola comercial, los peces aparentemente sanos, fueron inmovilizados y sacrificados, usando cloroformo. Se tomaron muestras de las regiones cardial, fúndica y pilórica, y se procesaron histológicamente. En su conjunto, el estómago presentaba una apariencia de “J”. El esófago estaba situado cranealmente al estómago, pero no se observó un esfínter que los separara. Caudalmente, un esfínter pilórico separaba al estómago del intestino proximal. El estómago contenía tres regiones: cardiaca, fúndica y pilórica. La totalidad de la superficie estomacal se encontraba recubierta por un epitelio cilíndrico, que contenía mucina en el citoplasma apical. Solamente las regiones cardiaca y fúndica tenían glándulas gástricas en la lámina propia, que eran más desarrolladas en la región fúndica. La túnica muscular poseía células musculares lisas con una orientación interna circular y externa longitudinal. La histoquímica mediante la mucina reveló la presencia solo de mucina neutra en el estómago. Los resultados obtenidos en este estudio sugieren que la ausencia de glándulas gástricas en el píloro, pudiera ser el resultado de una adaptación de esta especie para reducir la cantidad de ácido que penetra en el intestino proximal; por tanto, pudiera ayudar al medio alcalino a maximizar las acciones de las enzimas pancreáticas en el intestino proximal. La sola presencia de mucina neutra en el estómago actuaría como amortiguador contra el elevado contenido ácido del estómago. Las mucinas neutras también están asociadas con el transporte de micromoléculas.

Evaluation of glucosamine and snail mucin on the progression of experimental knee osteoarthritis in dogs / Evaluación de la glucosamina y mucina de caracol en la progresión de la osteoartritis experimental de rodilla en perros

This study evaluated the effect of oral glucosamine and intramuscular injection (IM) of snail mucin on the progression of experimental osteoarthritis (OA) in dogs. Twenty adult mongrels with mean body weight (12.4±1.8 kg) were used. Experimental OA was induced surgically using the groove model. The dogs were randomly divided into three groups following radiographic evidence of OA. Group one (control) comprised of ten dogs treated with normal saline twice weekly for four weeks following OA. Group two comprised of five dogs treated with 10mg/kg of oral glucosamine daily for four weeks. Group three comprised of five dogs treated with 5mg/kg intramuscular injection of 5% solution of snail mucin twice weekly for four weeks. Blood was obtained from the cephalic vein before surgical arthrotomy, after surgical arthrotomy, immediately after radiographic confirmation of OA (Week 0) and at two weeks interval up to 4 weeks of treatment. Efficacy of the drugs was assessed by changes in plasma IL-6 and MMP-3, while safety was determined using the changes in packed cell volume (PCV), total white blood cell counts (WBC) and observable adverse reactions associated with the administration of the drugs. In this study, the PCV and WBC did not differ significantly (P> 0.05) from the control group. Plasma IL-6 and MMP-3 were significantly (P< 0.05) lower both in glucosamine-treated and snail mucin-treated dogs up to week 4 of treatment when compared with the control group. However, there were no significant (P > 0.05) differences in IL-6 and MMP-3 between the two treatment groups. In addition, painful swelling at the site of injection was observed in dogs treated with snail mucin, while no adverse reaction was observed in dogs treated with oral glucosamine. It was therefore concluded that both oral glucosamine and IM injection of snail mucin comparably modified the progression of OA. However, owing to the adverse reaction noted with IM injection of snail mucin, further study is required to determine the most appropriate route of administration.

Se evaluaron los efectos de la glucosamina oral y la inyección intramuscular (IM) de mucina de caracol en la progresión de la osteoartritis (OA) experimental en perros. Fueron utilizados 20 perros mestizos adultos con un peso medio de 12,4±1,8 kg. La OA experimental se indujo quirúrgicamente mediante el modelo de ranura. Los animales se dividieron aleatoriamente en tres grupos después de la evidencia radiográfica de OA. El grupo 1 (control, 10 perros) fue tratado con una solución salina normal dos veces por semana durante cuatro semanas. El grupo 2 (5 perros) fue tratado con 10 mg/kg de glucosamina oral al día por cuatro semanas, y el grupo 3 (5 perros) fue tratado con 5 mg/kg IM de una solución de mucina de caracol al 5% dos veces por semana durante cuatro semanas. Se obtuvieron muestras de sangre desde la vena cefálica previo a la artrotomía quirúrgica, después de la artrotomía e inmediatamente después de la confirmación radiográfica de OA (semana 0), y en el intervalo de dos semanas hasta cuatro semanas de tratamiento. La eficacia de los fármacos se evaluó por los cambios plasmáticos de IL-6 y MMP-3, mientras que la seguridad, se determinó por los cambios en el volumen del hematocrito (VH), el recuento total de glóbulos blancos (RGB), y la observación de reacciones adversas asociadas a la administración de fármacos. El VH y RGB no difirieron significativamente (P>0,05) en el grupo control. Los niveles de IL-6 y MMP-3 plasmática fueron significativamente más bajas (P<0,05) en los perros tratados con glucosamina y mucina de caracol hasta 4 semanas, en comparación con el grupo control. Sin embargo, no hubo diferencias significativas (P>0,05) en la IL-6 y MMP-3 entre los dos grupos de tratamiento. Además, se observó un edema doloroso en el sitio de inyección de los perros tratados con mucina de caracol. En los perros tratados con glucosamina oral no se observó reacción adversa. Se concluye que tanto la glucosamina oral y la inyección IM de mucina de caracol modifican comparablemente la progresión de OA. Sin embargo, debido a la reacción adversa observada con la inyección IM de mucina caracol, se necesitan estudios adicionales para determinar la vía de administración más adecuada.

In vitro fluoride release and tensile bond Strength of a polymeric intra-buccal bioadhesive / Liberación in vitro de flúor y fuerza de tracción de un bioadhesivo polimérico intra-bucal

The intra-buccal polymeric bioadhesive systems that can stay adhered to the oral soft tissues for drug programmed release, with the preventive and/or therapeutic purpose has been employed for large clinical situations. A system based on hydroxypropyl methyl cellulose/Carbopol 934'/magnesium stearate (HPMC/Cp/StMg) was developed having the sodium fluoride as active principle. This kind of system was evaluated according to its resistance to the removal by means of physical test of tensile strength. Swine buccal mucosa extracted immediately after animals' sacrifice was employed as substrate for the physical trials, to obtain 16 test bodies. Artificial saliva with or without mucin was used to involve the substrate/bioadhesive system sets during the trials. Artificial salivas viscosity was determined by means of Brookfield viscometer, showing the artificial saliva with mucin 10.0 cP, and the artificial saliva without mucin 7.5 cP. The tensile strength assays showed the following averages: for the group "artificial saliva with mucin" - 12.89 Pa, and for the group "without mucin" - 12.35 Pa. Statistical analysis showed no significant difference between the assays for both artificial salivas, and it was possible to conclude that the variable mucin did not interfered with the bioadhesion process for the polymeric devices. The device was able to release fluoride in a safe, efficient and constant way up to 8 hours.

Los sistemas bioadhesivos poliméricos intra-bucales pueden permanecer adheridos a los tejidos blandos orales para una liberación programada de fármacos, con finalidad preventiva y/o propósito terapéutico han sido empleados en diversas situaciones clínicas. Un sistema basado en Hidroxipropilmetilcelulosa/Carbopol934Ô/ estearato de magnesio (HPMC/Cp/StMg) fue desarrollado con fluorato de sodio como principio activo. Este tipo de sistema fue evaluado de acuerdo a su resistencia a la eliminación física por medio de pruebas de resistencia a la tracción. Mucosas bucales de cerdos fueron tomadas inmediatamente después del sacrificio de los animales y se utilizaron como sustrato para las pruebas físicas, obteniendo 16 cuerpos de prueba. Saliva artificial con o sin mucina fue utilizada para participar como parte del sistema sustrato/bioadesivo durante los ensayos. La viscosidad de la saliva artificial, se determinó mediante un viscosímetro Brookfield, mostrando la saliva artificial con mucina 10,0 cP y saliva artificial sin mucina 7,5 cP. Las pruebas de resistencia a la tracción mostraron los siguientes promedios: para la "saliva artificial con mucina" - 12,89 Pa, y para el grupo "sin mucina" - 12,35 Pa. El análisis estadístico no mostró diferencias significativas entre las pruebas de saliva artificial, y es posible concluir que la variable de mucina no interfiere con el proceso de bioadhesión del dispositivo polimérico. El dispositivo fue capaz de liberar fluor de forma segura, eficiente y constante durante un máximo de hasta 8 horas.