Navigating surgical anatomy of the Denonvilliers' fascia and dissection planes of the anterior mesorectum with a cadaveric simulation model.

Anterior dissection of the rectum in the male pelvis represents one of the most complex phases of total meso-rectal excision. However, the possible existence of different anatomical planes is controversial and the exact anatomical topography of Denonvilliers' fascia is still debated. The aim of the study is to accurately define in a cadaveric simulation model the existence and boundaries of Denonvilliers' fascia, identifying the anatomical planes suitable for surgical dissection. The pelvises of 31 formalin-preserved male cadavers were dissected. Careful and detailed dissection was carried out to visualize the anatomical structures and the potential dissection planes, simulating an anterior meso-rectum dissection. Denonvilliers' fascia was identified in 100% of the pelvises, as a single-layer fascia that originates from the peritoneal reflection and descends until its firm adhesion to the prostate capsule. The fascia divides the space providing an anterior and a posterior plane. Anteriorly to the fascia, during the caudal dissection, its firm adhesion to the prostate capsule forces to section it sharply. The cadaveric simulation model allowed an accurate description of Denonvilliers' fascia, defining several planes for anterior dissection of the meso-rectum.

Estudio prospectivo de los valores de hormonas y péptidos relacionados con el metabolismo glucolipídico en pacientes obesos mórbidos sometidos a una gastrectomía vertical / Prospective study of gluco-lipidic hormone and peptide levels in morbidly obese patients after sleeve gastrectomy

INTRODUCCIÓN: Diferentes hormonas y péptidos implicados en el apetito y el metabolismo lipídico e hidrocarbonado se han estudiado en relación con la obesidad mórbida y su variación tras cirugía bariátrica. El objetivo de nuestro trabajo es evaluar las variaciones de diferentes moléculas relacionadas con el metabolismo glucolipídico durante el primer año tras una gastrectomía vertical en pacientes obesos mórbidos. MATERIAL Y MÉTODO: Estudio prospectivo en pacientes operados mediante gastrectomía vertical entre noviembre de 2009 y enero de 2011. Se determinaron y analizaron las variaciones en diferentes parámetros clínicos, antropométricos y analíticos relacionados con el metabolismo glucolipídico en todos los pacientes en el preoperatorio, al primer y quinto días, al mes, a los 6 meses y al año postoperatorio, realizando el estudio estadístico con ayuda del programa SPSS 20.0. RESULTADOS: De los 20 pacientes estudiados, el 60% eran mujeres con una mediana de edad de 45 años. La mediana del índice de masa corporal (IMC) preoperatorio fue de 48,5 kg/m2 y el 70% padecían síndrome de apnea obstructiva del sueño (SAOS), el 65% hipertensión arterial (HTA), el 45% dislipidemia y el 40% diabetes mellitus. Al año de la cirugía, el porcentaje de exceso de IMC perdido fue del 72% y la tasa de curación o mejoría de la dislipidemia fue del 100%, de diabetes el 87,5%, de HTA el 84,6% y de SAOS el 57,1%. En ese período los niveles de glucemia en ayunas disminuyeron de forma significativa (p < 0,001), mostrando los niveles de IGF-1 y colesterol HDL un aumento significativo. Los niveles de adiponectina aumentaron y los de leptina (p = 0,003), insulina (p = 0,004) y triglicéridos (p = 0,016) disminuyeron de forma significativa al año de la intervención. Los valores de ACTH (que disminuyeron durante los 6 primeros meses), hemoglobina glucosilada, colesterol total y LDL no experimentaron cambios significativos al año de la intervención. CONCLUSIÓN: La gastrectomía vertical es una técnica que presenta buenos resultados ponderales y de curación de comorbilidades, produciendo modificaciones significativas durante el primer año postoperatorio en los niveles sanguíneos de diferentes parámetros relacionados con el metabolismo glucolipídico como la glucosa, IGF-1, insulina, leptina, triglicéridos y colesterol HDL

INTRODUCTION: Different hormones and peptides involved in lipid and carbohydrate metabolism have been studied in relation to morbid obesity and its variation after bariatric surgery. The aim of this study is toevaluate variations in different molecules related to glico-lipidic metabolism during the first year after sleeve gastrectomy in morbidly obese patients. MATERIAL AND METHODS: Prospective study in patients undergoing sleeve gastrectomy between November 2009 and January 2011. We analyzed changes in different clinical, anthropometric and analytic parameters related with glico-lipidic metabolism in all patients in the preoperative period, first postoperative day, fifth day, one month, 6 months and one year after surgery. Statistical analysis was performed using SPSS 20.0. RESULTS: We included 20 patients, 60% were women with a median of age of 45 years. Median of body mass index (IMC) was 48,5 kg/m2 and 70% had obstructive sleep apnea syndrome (SAOS), 65% arterial hypertension (HTA), 45% dyslipidemia and 40% diabetes mellitus. One year after surgery, the percentage of excess of BMI loss was 72% and the rate of cure or improvement of dyslipidemia was 100%, diabetes 87,5%, HTA 84,6% and SAOS 57,1%. At this time, glycemia levels decreased significantly (P < .001), and levels of IGF-1 and HDL-cholesterol increased significantly. Levels of adiponectine increased and leptine (P = .003), insulin (P = .004) and triglycerides (P = .016) decreased significantly one year after the surgery. ACTH levels (that decreased during first 6 months after surgery), glycosilated hemoglobin, total cholesterol and LDL-cholesterol had no changes one year after surgery. CONCLUSIONS: Sleeve gastrectomy is a surgical technique with good results of weight loss and cure of comorbidities. This procedure induces significant modifications in blood levels of glico-lipidic metabolism related peptides and hormones, such as glucose, IGF-1, insulin, leptin, triglycerides and HDL-cholesterol

A prospective study on inflammatory parameters in obese patients after sleeve gastrectomy.

Different hormones and peptides involved in inflammation have been studied in and related to obesity. The aim of our work is to assess the variations of different molecules related to inflammation in obese patients during the first year following sleeve gastrectomy. This was a prospective study on patients who underwent sleeve gastrectomy. The variations in different clinical, anthropometric, and analytical parameters related to inflammation were determined and analysed in all patients at the preoperative visit and at the first and fifth days, first and sixth months, and 1 year following surgery. We enrolled 20 patients to the study. The median body mass index (BMI) before intervention was 48.5 kg/m2. With respect to comorbidities, 70% of the patients had obstructive sleep apnoea syndrome (OSA), 65% high blood pressure, 45% dyslipidaemia, and 40% diabetes mellitus (DM). The median percentage of BMI lost (%BMIL) 1 year after the intervention was 71%. The dyslipidaemia healing or improvement rate was 100%, whereas it was 87.5% for diabetes, 84.6% for hypertension, and 57.1% for OSA. During the 1-year postintervention period, the average levels of adiponectin increased, although not significantly, whereas those of leptin significantly decreased. In addition, the blood levels of MCP-1, IL-6, CRP, ferritin, and PAI-1 significantly decreased in that period. Sleeve gastrectomy is a surgical technique that is associated with improvements in body weight and comorbid conditions from the first postoperative months, which lead to significant variations in the levels of different inflammation-related parameters and a decrease in the levels of leptin, IL-6, CRP, MCP-1, ferritin, and serpin (PAI-1).

[Prospective study of gluco-lipidic hormone and peptide levels in morbidly obese patients after sleeve gastrectomy]. / Estudio prospectivo de los valores de hormonas y péptidos relacionados con el metabolismo glucolipídico en pacientes obesos mórbidos sometidos a una gastrectomía vertical.

INTRODUCTION: Different hormones and peptides involved in lipid and carbohydrate metabolism have been studied in relation to morbid obesity and its variation after bariatric surgery. The aim of this study is toevaluate variations in different molecules related to glico-lipidic metabolism during the first year after sleeve gastrectomy in morbidly obese patients. MATERIAL AND METHODS: Prospective study in patients undergoing sleeve gastrectomy between November 2009 and January 2011. We analyzed changes in different clinical, anthropometric and analytic parameters related with glico-lipidic metabolism in all patients in the preoperative period, first postoperative day, fifth day, one month, 6 months and one year after surgery. Statistical analysis was performed using SPSS 20.0. RESULTS: We included 20 patients, 60% were women with a median of age of 45 years. Median of body mass index (IMC) was 48,5 kg/m(2) and 70% had obstructive sleep apnea syndrome (SAOS), 65% arterial hypertension (HTA), 45% dyslipidemia and 40% diabetes mellitus. One year after surgery, the percentage of excess of BMI loss was 72% and the rate of cure or improvement of dyslipidemia was 100%, diabetes 87,5%, HTA 84,6% and SAOS 57,1%. At this time, glycemia levels decreased significantly (P<.001), and levels of IGF-1 and HDL-cholesterol increased significantly. Levels of adiponectine increased and leptine (P=.003), insulin (P=.004) and triglycerides (P=.016) decreased significantly one year after the surgery. ACTH levels (that decreased during first 6 months after surgery), glycosilated hemoglobin, total cholesterol and LDL-cholesterol had no changes one year after surgery. CONCLUSIONS: Sleeve gastrectomy is a surgical technique with good results of weight loss and cure of comorbidities. This procedure induces significant modifications in blood levels of glico-lipidic metabolism related peptides and hormones, such as glucose, IGF-1, insulin, leptin, triglycerides and HDL-cholesterol.

A lipoprotein source of cholesteryl esters is essential for proliferation of CEM-CCRF lymphoblastic cell line.

Tumour are characterised by a high content of cholesteryl esters (CEs) stored in lipid droplets purported to be due to a high rate of intracellular esterification of cholesterol. To verify whether and which pathways involved in CE accumulation are essential in tumour proliferation, the effect of CE deprivation, from both exogenous and endogenous sources, on CEM-CCRF cells was investigated. Cholesterol synthesis, esterification and content, low-density lipoprotein (LDL) binding and high-density lipoprotein (HDL)-CE uptake were evaluated in cultured in both conventional and delipidated bovine serum with or without oleic or linoleic acids, cholesteryl oleate, LDL and HDL. High content of CEs in lipid droplets in this cell line was due to esterification of both newly synthesised cholesterol and that obtained from hydrolysis of LDL; moreover, a significant amount of CE was derived from HDL-CE uptake. Cell proliferation was slightly affected by either acute or chronic treatment up to 400 µM with Sz-58035, an acyl-cholesteryl cholesterol esterification inhibitor (ACAT); although when the enzyme activity was continuously inhibited, CE content in lipid droplets was significantly higher than those in control cells. In these cells, analysis of intracellular and medium CEs revealed a profile reflecting the characteristics of bovine serum, suggesting a plasma origin of CE molecules. Cell proliferation arrest in delipidated medium was almost completely prevented in the first 72 h by LDL or HDL, although in subsequent cultures with LDL, it manifested an increasing mortality rate. This study suggests that high content of CEs in CEM-CCRF is mainly derived from plasma lipoproteins and that part of CEs stored in lipid droplets are obtained after being taken up from HDL. This route appears to be up-regulated according to cell requirements and involved in low levels of c-HDL during cancer. Moreover, the dependence of tumour cells on a source of lipoprotein provides a novel impetus in developing therapeutic strategies for use in the treatment of some tumours.

Altered cholesterol ester cycle in skin fibroblasts from patients with Alzheimer's disease.

Intracellular cholesterol metabolism was reported to modulate amyloid-beta (Abeta) generation in Alzheimer's disease (AD). Results presented herein demonstrated that, like brain cells, cultured skin fibroblasts from AD patients contained more cholesterol esters than fibroblasts from healthy subjects. Particularly, Oil Red-O, Nile Red, and filipin staining highlighted higher levels of neutral lipids which responded to inhibitors of acyl-coenzyme A:cholesterol acyl-transferase (ACAT-1), associated with an increase in free cholesterol. ACAT-1 mRNA levels increased significantly in AD fibroblasts, whereas those of sterol regulatory element binding protein-2, neutral cholesterol ester hydrolase, and ATP-binding cassette transporter member 1 were markedly down-regulated. Instead, mRNA levels of low-density lipoprotein receptor, hydroxy-methyl-glutaryl-coenzyme A reductase, caveolin-1, and amyloid-beta protein precursor (AbetaPP) were virtually unchanged. Notably, mRNA levels of both beta-site AbetaPP-cleaving enzyme 1 (BACE1) and neprilysin were significantly down-regulated. An increase in Abeta(40) and Abeta(42) immunostaining and a decrease in BACE1 active form were also found in AD versus control fibroblasts. Altogether, these findings support the hypothesis that the derangement of cholesterol homeostasis is a systemic alteration involving central but also peripheral cells of AD patients, and point to cholesterol ester levels in AD fibroblasts as an additional metabolic hallmark useful in the laboratory and clinical practice.

Antiprion activity of cholesterol esterification modulators: a comparative study using ex vivo sheep fibroblasts and lymphocytes and mouse neuroblastoma cell lines.

Our studies on the role of cholesterol homeostasis in the pathogenesis of scrapie revealed abnormal accumulation of cholesterol esters in ex vivo peripheral blood mononuclear cells (PBMCs) and skin fibroblasts from healthy and scrapie-affected sheep carrying a scrapie-susceptible genotype compared to sheep with a resistant genotype. Similar alterations were observed in mouse neuroblastoma N2a cell lines persistently infected with mouse-adapted 22L and RML strains of scrapie that showed up to threefold-higher cholesterol ester levels than parental N2a cells. We now report that proteinase K-resistant prion protein (PrPres)-producing cell populations of subclones from scrapie-infected cell lines were characterized by higher cholesterol ester levels than clone populations not producing PrPres. Treatments with a number of drugs known to interfere with different steps of cholesterol metabolism strongly reduced the accumulation of cholesterol esters in ex vivo PBMCs and skin fibroblasts from scrapie-affected sheep but had significantly less or no effect in their respective scrapie-resistant or uninfected counterparts. In scrapie-infected N2a cells, inhibition of cholesterol esters was associated with selective antiprion activity. Effective antiprion concentrations of cholesterol modulators (50% effective concentration [EC(50)] range, 1.4 to 40 microM) were comparable to those of antiprion reference compounds (EC(50) range, 0.6 to 10 microM). These data confirm our hypothesis that abnormal accumulation of cholesterol esters may represent a biological marker of susceptibility to prion infection/replication and a novel molecular target of potential clinical importance.

Modulation of cholesterol homeostasis by antiproliferative drugs in human pterygium fibroblasts.

PURPOSE: The authors have previously shown that the growth of cultured fibroblasts obtained from primary pterygia was associated with an increase in cholesterol esterification, suggesting that alterations of cholesterol homeostasis may be involved in the development and progression of this disorder. This investigation was conducted to determine whether antiproliferative agents such as pioglitazone (PIO) and everolimus (EVE) may inhibit proteins involved in the cholesterol ester cycle and the proliferation of pterygium fibroblasts (PF). METHODS: Quiescent normal conjunctival fibroblasts and PFs were treated with or without inhibitors of cell proliferation (PIO and EVE) or with inhibitors of cholesterol esterification-progesterone (Pg) and Sandoz compound (SaH)-and then were stimulated to growth by 10% fetal calf serum (FCS). Cell proliferation was assessed by counting cells. Trypan blue uptake was used to determine cell viability. mRNA and protein levels were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. RESULTS: PIO and EVE significantly abolished the increase in cholesterol esters, acyl-coenzyme A cholesterol acyltransferase (ACAT1), and multidrug resistance protein (MDR1) mRNA observed in growing cells. Each inhibitor upregulated ATP-binding cassette-A1 (ABCA1), neutral cholesterol ester hydrolase (NCEH) mRNA, and caveolin-1 expression in a manner similar to that of specific inhibitors of cholesterol esterification such as Pg and SaH. CONCLUSIONS: Intracellular modifications of cholesterol homeostasis may be relevant to pterygium development. Moreover, antiproliferative agents such as PIO and EVE may represent a potential topical medication in the prevention and inhibition of pterygium growth at an early stage, probably by modulation of cholesterol ester metabolism.

Critical role of stearoyl-CoA desaturase-1 (SCD1) in the onset of diet-induced hepatic insulin resistance.

Stearoyl-CoA desaturase-1 (SCD1) catalyzes the synthesis of monounsaturated fatty acids from saturated fatty acids. Mice with a targeted disruption of Scd1 gene locus are lean and display increased insulin sensitivity. To examine whether Scd1 activity is required for the development of diet-induced hepatic insulin resistance, we used a sequence-specific antisense oligodeoxynucleotide (ASO) to lower hepatic Scd1 expression in rats and mice with diet-induced insulin resistance. Treatment of rats with Scd1 ASO markedly decreased liver Scd1 expression (approximately 80%) and total Scd activity (approximately 50%) compared with that in rats treated with scrambled ASO (control). Insulin clamp studies revealed severe hepatic insulin resistance in high-fat-fed rats and mice that was completely reversed by 5 days of treatment with Scd1 ASO. The latter treatment decreased glucose production (by approximately 75%), gluconeogenesis, and glycogenolysis. Downregulation of Scd1 also led to increased Akt phosphorylation and marked decreases in the expression of glucose-6-phosphatase (Glc-6-Pase) and phosphoenolpyruvate carboxykinase (PEPCK). Thus, Scd1 is required for the onset of diet-induced hepatic insulin resistance.