Esophageal mucosal resection versus esophagectomy: a comparative study of surgical results in patients with advanced megaesophagus / Mucosectomia esofágica versus esofagectomia: estudo comparativo dos resultados cirúrgicos imediatos e tardios em pacientes operados por megaesôfago avançado

BACKGROUND: The surgical treatment of advanced megaesophagus has no consensus, being esophagectomy the more commonly used method. Since it has high morbimortality - inconvenient for benign disease -, in recent years an alternative has been introduced: the esophageal mucosal resection. AIM: To compare early and late results of the two techniques evaluating the operative time, length of ICU stay; postoperative hospitalization; total hospitalization; intra- and postoperative complication rates; mortality; and long-term results. METHODS: Were evaluated retrospectively 40 charts, 23 esophagectomies and 17 mucosectomies. In assessing postoperative results, interviews were conducted by using a specific questionnaire. RESULTS: Comparing the means of esophagectomy and mucosal resection, respectively, the data were: 1) surgical time - 310.2 min and 279.7 min (p> 0.05); 2) length of stay in ICU - 5 days and 2.53 days (p <0.05); 3) total time of hospitalization - 24.25 days and 20.76 days (p> 0.05); 4) length of hospital stay after surgery - 19.05 days and 14.94 days (p> 0.05); 5) presence of intraoperative complications - 65% and 18% (p <0.05); 6) the presence of postoperative complications - 65% and 35% (p> 0.05). In the assessment of late postoperative score (range 0-10) esophagectomy (n = 5) obtained 8.8 points and 8.8 points also got mucosal resection (n = 5). CONCLUSIONS: Esophageal mucosal resection proved to be good alternative for surgical treatment of megaesophagus. It was advantageous in the immediate postoperative period by presenting a lower average time in operation, the total hospitalization, ICU staying and complications rate. In the late postoperative period, the result was excellent and good in both operations. .

RACIONAL: O tratamento cirúrgico do megaesôfago avançado não é consensual sendo mais comumente usada a esofagectomia. Por tratar-se de técnica que apresenta maior morbimortalidade e empregada em doença benigna, foi introduzida nos últimos anos, como alternativa, a mucosectomia esofágica. OBJETIVO: Comparar os resultados imediatos e tardios das duas técnicas avaliando-se os tempos operatório, de internação em UTI, de internação do pós-operatório, de internação total; taxas de complicações intra-operatórias e pós-operatórias; taxa de mortalidade; e resultados a longo prazo. MÉTODOS: Foram avaliados 40 prontuários, retrospectivamente, sendo 23 esofagectomias e 17 mucosectomias. Na avaliação dos resultados pós-operatórios, foram realizadas entrevistas, mediante uso de questionário específico. RESULTADOS: Comparando-se as médias da esofagectomia e mucosectomia, respectivamente, os dados foram: 1) tempo cirúrgico - 310,2 min e 279,7 min (p>0,05); 2) tempo de internação em UTI - 5 dias e 2,53 dias (p<0,05); 3) tempo de internação total - 24,25 dias e 20,76 dias (p>0,05); 4) tempo de internação após a operação - 19,05 dias e 14,94 dias (p>0,05); 5) presença de complicações intra-operatórias - 65% e 18% (p<0,05); 6) presença de complicações pós-operatórias imediatas - 65% e 35% (p>0,05). Na avaliação do escore pós-operatório tardio (escala 0-10) a esofagectomia (n=5) obteve 8,8 pontos e também 8,8 pontos obteve a mucosectomia (n=5). CONCLUSÕES: A mucosectomia esofágica mostrou-se boa alternativa no tratamento cirúrgico do megaesôfago avançado. Foi vantajosa no pós-operatório imediato por apresentar menor média de tempo na operação, na internação total, na UTI e no índice de complicações. No pós-operatório tardio, o resultado foi excelente e bom nas duas operações. .

Fatty acid composition of Drosophila photoreceptor light-sensitive microvilli

Phototransduction, the mechanism underlying the electrical response to light in photoreceptor cells, has been thoroughly investigated in Drosophila melanogaster, an essential model in signal transduction research. These cells present a highly specialized photosensitive membrane consisting of thousands of microvilli forming a prominent structure termed a rhabdomere. These microvilli encompass the phototransduction proteins, most of which are transmembrane and exclusively rhabdomeric. Rhabdomere membrane lipids play a crucial role in the activation of the transient receptor potential ionic channels (TRP and TRPL) responsible for initiating the photoresponse. Despite its importance, rhabdomere lipid composition has not been established. We developed a novel preparation enriched in rhabdomere membranes to perform a thorough characterization of the lipidomics of Drosophila rhabdomeres. Isolated eyes (500) were homogenized and subjected to a differential centrifugation protocol that generates a fraction enriched in rhabdomere membrane. Lipids extracted from this preparation were identified and quantified by gas chromatography coupled to mass spectrometry. We found an abundance of low sterol esters (C16:0, C18:0), highly abundant and diverse triglycerides, free fatty acids, a moderate variety of mono and diacyglycerols (C:16:0, 18:0, C18:1) and abundant phospholipids (principally C18:2). This preparation opens a new avenue for investigating essential aspects of phototransduction.

Location matters: the endoplasmic reticulum and protein trafficking in dendrites

Neurons are highly polarized, but the trafficking mechanisms that operate in these cells and the topological organization of their secretory organelles are still poorly understood. Particularly incipient is our knowledge of the role of the neuronal endoplasmic reticulum. Here we review the current understanding of the endoplasmic reticulum in neurons, its structure, composition, dendritic distribution and dynamics. We also focus on the trafficking of proteins through the dendritic endoplasmic reticulum, emphasizing the relevance of transport, retention, assembly of multi-subunit protein complexes and export. We additionally discuss the roles of the dendritic endoplasmic reticulum in synaptic plasticity.

The expression and localization of inhibin isotypes in mouse testis during postnatal development

Inhibin, which is important for normal gonadal function, acts on the pituitary gonadotropins to suppress folliclestimulating hormone (FSH) secretion. The level and cellular localization of the inhibin isotypes, alpha, beta(A) and beta(B), in the testis of mice were examined during postnatal development in order to determine if inhibin expression is related to testicular maturation. Mouse testes were sampled on postnatal days (PNDs) 1, 3, 6, 18, 48 and 120, and analyzed by Western blotting and immunofluorescence. Western blot analysis showed very low levels of inhibin alpha, beta(A) and beta(B) expression in the testes at days 1 to 6 after birth. The levels then increased gradually from PND 18 to 48-120, and there were significant peaks at PND 48. Inhibin alpha, beta(A) and beta(B) were detected in testicular cells during postnatal development using immunohistochemistry. The immunoreactivity of inhibin alpha was rarely observed in testicular cells during PND 1 to 6, or in the cytoplasmic process of Sertoli cells surrounding the germ cells and interstitial cells during PND 18 to 120. Inhibin beta(A) and beta(B) immunoreactivity was rarely observed in the testis from PND 1 to 6. On the other hand, it was observed in some spermatogonial cells, as well as in the interstitial space between PND 48 and PND 120. We conclude that the expression of inhibin isotypes increases progressively in the testis of mice with increasing postnatal age, suggesting that inhibin is associated with a negative feedback signal for FSH in testicular maturation.

Involvement of Sox-4 in the cytochrome c-dependent AIF-independent apoptotic pathway in HeLa cells induced by delta12-prostaglandin J2

delta12-Prostaglandin (PG) J2 is known to elicit an anti-neoplastic effects via apoptosis induction. Previous study showed delta12-PGJ2-induced apoptosis utilized caspase cascade through cytochrome c-dependent pathways in HeLa cells. In this study, the cellular mechanism of delta12-PGJ2- induced apoptosis in HeLa cells, specifically, the role of two mitochondrial factors; bcl-2 and apoptosis-inducing factor (AIF) was investigated. Bcl-2 attenuated delta12-PGJ2-induced caspase activation, loss of mitochondrial transmembrane potential (delta psi m), nuclear fragmentation, DNA laddering, and growth curve inhibition for approximately 24 h, but not for longer time. AIF was not released from mitochondria, even if the delta psi m was dissipated. One of the earliest events observed in delta12-PGJ2-induced apoptotic events was dissipation of delta psi m, the process known to be inhibited by bcl-2. Pre-treatment of z-VAD- fmk, the pan-caspase inhibitor, resulted in the attenuation of delta psi m depolarization in delta12-PGJ2- induced apoptosis. Up-regulation of Sox-4 protein by delta12-PGJ2 was observed in HeLa and bcl-2 overexpressing HeLa B4 cell lines. Bcl-2 overexpression did not attenuate the expression of Sox-4 and its expression coincided with other apoptotic events. These results suggest that delta12-PGJ2 induced Sox-4 expression may activate another upstream caspases excluding the caspase 9-caspase 3 cascade of mitochondrial pathway. These and previous findings together suggest that delta12-PGJ2-induced apoptosis in HeLa cells is caspase-dependent, AIF-independent events which may be affected by Sox-4 protein expression up-regulated by delta12-PGJ2.

Lipid rafts are important for the association of RANK and TRAF6

Rafts, cholesterol- and sphingolipid-rich membrane microdomains, have been shown to play an important role in immune cell activation. More recently rafts were implicated in the signal transduction by members of the TNF receptor (TNFR) family. In this study, we provide evidences that the raft microdomain has a crucial role in RANK (receptor activator of NF-kappaB) signaling. We found that the majority of the ectopically expressed RANK and substantial portion of endogenous TRAF2 and TRAF6 were detected in the low-density raft fractions. In addition, TRAF6 association with rafts was increased by RANKL stimulation. The disruption of rafts blocked the TRAF6 translocation by RANK ligand and impeded the interaction between RANK and TRAF6. Our observations demonstrate that proper RANK signaling requires the function of raft membrane microdomains.