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1.
Int J Obes (Lond) ; 38(6): 865-72, 2014 Jun.
Article En | MEDLINE | ID: mdl-24126816

OBJECTIVE: FSP27 KO mice showed enhanced expression of mitochondrial genes, increased mitochondrial activity and smaller lipid droplets. Here, we aimed to investigate lipid droplet protein (CIDEC/FSP27 and perilipinA (PLIN1)) gene expression in human adipose tissue in association with obesity, insulin resistance and mitochondrial gene expression. DESIGN AND SUBJECTS: In cohort 1, CIDEC/FSP27, PLIN1, adipogenic (FASN, ACACA, PPARG, GLUT4) and mitochondrial (PPARGC1A, PPARGC1B, TFAM, MT-CO3) gene expression were analyzed in 171 adipose tissue samples (88 visceral adipose tissue (VAT) and 83 subcutaneous adipose tissue (SAT) depots) and in a time course experiment in human subcutaneous and visceral preadipocytes using real-time PCR. In cohort 2, the effects of bariatric surgery-induced weight loss were also evaluated in six caucasian morbidly obese women. Additionally, in cohort 2 FSP27 and PLIN1 protein levels were measured using western blotting. RESULTS: CIDEC/FSP27 (1.03±0.52 vs 0.49±0.23 relative gene expression unit (R.U.), P<0.0001) and PLIN1 (1.32±0.82 vs 0.63±0.42 R.U., P<0.0001) gene were significantly more expressed in SAT than in VAT. In VAT, CIDEC/FSP27 and PLIN1 gene expression decreased with body mass index, percent fat mass, fasting glucose, fasting insulin, HOMA and were positively associated with adipogenic (PPARG, GLUT4, FASN and ACACA) and mitochondrial biogenesis (PPARGC1A, PPARGC1B, TFAM and MT-CO3)-related genes. Mitochondrial gene expression increased during adipocyte differentiation in parallel to FSP27 and PLIN1 and other adipogenic genes. After bariatric surgery-induced weight loss, PLIN1 and CIDEC/FSP27 gene and protein expression in SAT increased significantly in parallel to adipogenic and mitochondrial genes. CONCLUSION: These findings suggest a positive functional interaction between CIDEC/FSP27, PLIN1 and mitochondrial biogenesis-related genes in human adipose tissue.


Carrier Proteins/metabolism , Genes, Mitochondrial , Insulin Resistance , Obesity, Morbid/metabolism , Proteins/metabolism , Subcutaneous Fat/metabolism , Weight Loss , Animals , Apoptosis Regulatory Proteins , Blotting, Western , Cells, Cultured , Female , Humans , Mice , Mice, Knockout , Obesity, Morbid/genetics , Obesity, Morbid/surgery , Perilipin-1 , Phosphoproteins/metabolism , Weight Loss/genetics
2.
Int J Obes (Lond) ; 38(5): 737-45, 2014 May.
Article En | MEDLINE | ID: mdl-23999197

OBJECTIVE: The purpose of this study was to investigate the expression of human adipose tissue protein 53 (p53) in subjects who varied widely in terms of obesity and insulin resistance. We also analyzed different in vivo and in vitro models to try to comprehend the associations found in humans. METHODS: p53 was analyzed in human adipose and isolated adipocytes, in high fat-fed and GLP-1R KO mice, during in vitro adipogenesis, and in adipocytes after high glucose, rosiglitazone and inflammatory conditions. The effects of surgery-induced weight loss and ex vivo metformin were also evaluated. RESULTS: Omental (OM) p53 gene expression (+27%, P=0.001) and protein (+11%, P=0.04) were increased in obese subjects and high fat diet-induced obese mice (+86%, P=0.018). Although the obesity-associated inflammatory milieu was associated with increased OM p53, this was negatively related to insulin resistance and glycated hemoglobin, and positively with biomarkers for insulin sensitivity. Multiple linear regression analyses revealed that glycated hemoglobin (P<0.0001) and body mass index (P=0.048) contributed independently to explain 13.7% (P<0.0001) of the OM p53 variance. Accordingly, the improvement of insulin sensitivity with surgery-induced weight loss (+51%, P=0.01) and metformin (+42%, P=0.02) led to increased adipose p53. While the glucose-intolerant GLP-1R KO mice showed decreased mesenteric p53 (-45.4%, P=0.017), high glucose led to decreased p53 in pre-adipocytes (-27%, P<0.0001). Inflammatory treatments led to increased p53 (+35%, P<0.0001), while Rs downregulated this expression (-40%, P=0.005) in mature adipocytes. CONCLUSION: Inflammation and insulin resistance exert dual effects on adipose p53, which seems to be the final result of these opposing forces.


Adipocytes/metabolism , Adipose Tissue/metabolism , Genes, p53 , Inflammation/metabolism , Insulin Resistance , Obesity/metabolism , Omentum/metabolism , Adipogenesis , Analysis of Variance , Animals , Bariatric Surgery , Diet, High-Fat , Enzyme-Linked Immunosorbent Assay , Female , Gene Expression , Humans , Inflammation/genetics , Male , Metformin/pharmacology , Mice , Mice, Knockout , Obesity/genetics , Omentum/surgery , Rosiglitazone , Thiazolidinediones/pharmacology
3.
Int J Obes (Lond) ; 37(12): 1532-8, 2013 Dec.
Article En | MEDLINE | ID: mdl-23478426

BACKGROUND: Surfactant protein-D (SFTPD) is a component of the lung innate immunity that enhances clearance of pathogens and modulates inflammatory responses. An inverse association of putative, lung-derived circulating SFTPD with obesity has been reported but no information is available concerning possible SFTPD gene expression in human adipose tissue. METHODS: SFTPD gene expression was analyzed in human omental (OM; n=156) and subcutaneous (SC; n=106) adipose tissue, and in isolated fat cells (n=12) in association with measures of obesity and glucose tolerance. RESULTS: SFTPD gene was expressed in human adipose tissue and adipocytes. This expression was decreased in OM and SC adipose tissue from obese subjects with (-47%, P<0.0001; and -37%, P=0.048) and without (-34%, P=0.001; and -22%, P=0.08; respectively) type 2 diabetes when compared with the control group. Indeed, OM SFTPD was inversely associated with body mass index (r=-0.33, P<0.0001), percent fat mass (r=-0.36, P<0.0001), waist perimeter (r=-0.26, P=0.002), diastolic blood pressure (r=-0.21, P=0.018) and fasting glucose (r=-0.21, P=0.012); and positively linked to the expression of insulin receptor substrate 1 (IRS1; r=0.25, P=0.004), perilipin A (PLIN; r=0.38, P=0.007) and fatty acid synthase (FASN; r=0.36, P<0.0001). Accordingly, increased SFTPD (4.5-fold, P=0.02) was detected in isolated adipocytes when compared with the stromal-vascular cell fraction, in parallel to IRS1, FASN and PLIN. CONCLUSIONS: Both OM and SC adipose tissue (mainly mature adipocytes) express SFTPD. This expression decreases with obesity and impaired glucose tolerance.


Immunity, Innate , Obesity/immunology , Pulmonary Surfactant-Associated Protein D/metabolism , Subcutaneous Fat/immunology , Body Mass Index , Enzyme-Linked Immunosorbent Assay , Female , Humans , Inflammation/immunology , Male , Middle Aged , Obesity/complications , Obesity/metabolism , Omentum/metabolism , Polymorphism, Single Nucleotide , Pulmonary Surfactant-Associated Protein D/immunology , Subcutaneous Fat/metabolism
4.
Int J Obes (Lond) ; 36(2): 320-4, 2012 Feb.
Article En | MEDLINE | ID: mdl-21610697

Differentiation and metabolism of adipose tissue are modulated by thyroid hormones (THs), but relatively little is known about the metabolism of THs in this tissue. Expression of the genes for type I iodothyronine 5'-deiodinase (D1), leptin (LEP) and stearoyl-CoA desaturase 1 (SCD-1) was evaluated in omental (OM) and subcutaneous (SC) fat using a cohort of 70 humans. Activities of iodothyronine deiodinases (D1, D2 and D3) were assessed in a randomly selected subpopulation of 19 subjects. D1 expression was upregulated in both OM (P=0.011) and SC (P=0.003) fat of obese subjects. Concomitantly, OM (P=0.002) and SC (P=0.028) LEP expression were increased in obesity, associated with both D1 mRNA (r=0.315, P=0.014) and activity (r=0.647, P=0.023) and inversely related to SCD-1 (r=-0.266, P=0.034) expression in SC fat. Also D1 (but not D2 and D3) activity was increased in OM (∼fourfold, P=0.010) and SC (∼eightfold, P=0.004) fat of obese when compared with non-obese subjects and correlated in both OM (r=0.528, P=0.036) and SC (r=0.749, P=0.005) fat with body mass index. Our results document increased D1 gene expression and activity in adipose tissue of obese humans and suggest a role of 3,5,3'-triiodo-L-thyronine formed by D1 in response to leptin in the modulation of adipose tissue metabolism.


Adipose Tissue, White/metabolism , Iodide Peroxidase/metabolism , Leptin/metabolism , Obesity/enzymology , Thyroid Hormone Receptors alpha/metabolism , Body Mass Index , Cell Differentiation/genetics , Cohort Studies , Cross-Sectional Studies , Down-Regulation , Female , Gene Expression Regulation, Enzymologic , Humans , Iodide Peroxidase/genetics , Leptin/genetics , Male , Polymerase Chain Reaction , RNA, Messenger/metabolism , Thyroid Hormone Receptors alpha/genetics , Transcription Factors/genetics , Transcription Factors/metabolism
10.
Hernia ; 12(3): 289-97, 2008 Jun.
Article En | MEDLINE | ID: mdl-18188503

BACKGROUND: Obturator hernia is an uncommon but important cause of intestinal obstruction. METHODS: Retrospective study of 16 patients undergoing surgery for obturator hernia in a 20-year period. RESULTS: All patients were elderly women. Low body mass index and multiparity were predisposing factors. Mean time from onset of symptoms to consultation was 4.1 days. The preoperative diagnosis was intestinal obstruction of unknown etiology in 13 cases and intestinal obstruction due to obturator hernia in three (diagnosis by CT). The rate of strangulated hernias was 75% and the perforation rate was 56.3%. Intestinal resection was required in 12 cases. Hernia repair was performed using polypropylene mesh in 11 cases and by means of simple suture and apposition of the peritoneum in five. Morbidity was 75% and mortality was 18.8%. CONCLUSIONS: Early diagnosis--we recommend CT in thin, elderly, multiparous women with intestinal obstruction--and early treatment can reduce complications and mortality.


Algorithms , Hernia, Obturator/diagnosis , Hernia, Obturator/surgery , Aged , Aged, 80 and over , Chi-Square Distribution , Female , Hernia, Obturator/complications , History, 17th Century , Humans , Intestinal Obstruction/etiology , Retrospective Studies , Risk Factors , Tomography, X-Ray Computed
12.
Colorectal Dis ; 10(7): 701-7, 2008 Sep.
Article En | MEDLINE | ID: mdl-18005196

OBJECTIVE: Intestinal perforation due to foreign body (FB) ingestion is rare (1%). We describe our experience in treating these lesions surgically. METHOD: From 1995 to 2006, data were collected prospectively in 33 patients (18 women and 15 men; mean age 64 years) operated on for intestinal perforation due to an ingested FB. The type of object, preoperative diagnosis, perforation site, treatment, morbidity and mortality were reviewed. RESULTS: Foreign body ingestion was predominantly involuntary (88%). The mean time from ingestion to perforation was 10.4 days. The most frequently ingested objects were dietary FB (n = 21) and toothpicks (n = 6). The most frequent predisposing factors were dentures or an orthodontic appliance (73%). The most common preoperative diagnoses were acute abdomen of uncertain origin (n = 7), acute appendicitis (n = 7) and acute diverticulitis (n = 5). Pneumoperitoneum was observed in 10 cases. The diagnosis was reached during laparotomy in 30 (91%) cases. The most frequent perforation site was the colorectal region (n = 18, 54.5%), followed by the terminal ileum (n = 7, 21.2%); intraperitoneal perforation was the most common (n = 30, 91%). All cases had abdominal contamination and 22 (66.7%) had diffuse peritonitis. Treatment was always by surgery and antibiotics. Thirteen patients required a colostomy. Morbidity was 57.6% (n = 19) and mortality 6.1% (n = 2). CONCLUSION: Intestinal perforation by a foreign body is rare and normally affects the sigmoid colon, rectum or distal ileum. Dentures are a common risk factor. Patients are rarely aware of foreign body ingestion. Dietary FB and toothpicks are the most commonly ingested objects. Treatment consists of surgery and antibiotics. Appendicitis and acute diverticulitis should be considered in the differential diagnosis.


Foreign-Body Migration/complications , Intestinal Perforation/etiology , Intestinal Perforation/surgery , Abdominal Pain/etiology , Adult , Aged , Aged, 80 and over , Cohort Studies , Digestive System Surgical Procedures , Female , Humans , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Male , Middle Aged , Prospective Studies , Risk Factors , Young Adult
13.
Colorectal Dis ; 9(6): 543-8, 2007 Jul.
Article En | MEDLINE | ID: mdl-17573750

OBJECTIVE: The discovery of foreign bodies (FB) in the rectum is an infrequent clinical problem. Most commonly, FB are introduced through the anal passage or reach the rectum after oral ingestion. We describe our experience in the diagnosis and treatment of FB retained in the rectum. METHOD: From 1997 to 2004, data were collected prospectively in 30 patients (20 men and 10 women; median age 42.5 years). Extraction method, size and type of object, and postextraction evolution were reviewed. RESULTS: The FB was introduced anally in 16 cases and by oral ingestion in 14. Principal associated factors were: mental disorder in 11, penitentiary confinement in two, and drug and alcohol intake in two. Recent sexual activity had taken place in 14 cases. The size and nature of the FB were varied. The most frequent symptom was constipation with or without pelvic or anal discomfort (n = 23, 77%). Treatment consisted of spontaneous ejection (n = 2), digital extraction with or without enemas (n = 10), digital extraction under local/regional anaesthesia after fragmentation (n = 11) and regional exploratory laparotomy under general anaesthesia (n = 7). Grade I rectal trauma was the most common (n = 23, 77%). Six patients required colostomy. Four patients (13.5%) suffered complications and none died. Only 17 patients were hospitalized, with a mean stay of 6 days. All patients recovered without sequelae. CONCLUSION: The diagnosis of rectal FB should be suspected when faced with low pelvic or perianal abdominal pain and/or rectal haemorrhage within the context of an unconvincing story in patients without a history of recent instrumental rectal exploration for therapeutic or diagnostic purposes. Because of potential complications, FB in the rectum should be considered a serious condition that must be treated without delay.


Foreign Bodies/diagnosis , Foreign Bodies/surgery , Rectum , Adult , Alcoholism/epidemiology , Comorbidity , Constipation/epidemiology , Foreign Bodies/epidemiology , Foreign Bodies/etiology , Foreign Bodies/psychology , Humans , Mental Disorders/epidemiology , Self-Injurious Behavior/epidemiology
15.
Clin Endocrinol (Oxf) ; 67(1): 29-33, 2007 Jul.
Article En | MEDLINE | ID: mdl-17466010

UNLABELLED: A diagnosis of bilateral pheochromocytoma warrants exclusion of hereditary pheochromocytoma. OBJECTIVE: To describe the first case of a bilateral pheochromocytoma associated with V804M mutation in the RET proto-oncogene. PATIENTS: The index case was a 54-year-old man with bilateral adrenal masses discovered during a CT scan performed for other reasons. MEASUREMENTS: Genetic analysis included exons 8-11 and 13-17 in the RET proto-oncogene, all four exons and flanking intronic regions in the SDHD gene, all eight exons and flanking intronic regions in the SDHB, and all three exons in the VHL gene. RESULTS: Investigations revealed elevated urinary metanephrines (32.3 micromol/day), and laparoscopic bilateral adrenalectomy confirmed bilateral pheochromocytomas. A heterozygous V804M mutation in exon 14 of the RET was found in the index case and in four relatives. Total thyroidectomy, performed in four of five affected members in this kindred, disclosed a medullary thyroid carcinoma in the index case and in a 50-year-old woman, and nodular C-cell hyperplasia in the other two subjects. CONCLUSIONS: This clinical case suggests that individuals carrying the germline V804M mutation should be screened annually for the presence of pheochromocytoma.


Adrenal Gland Neoplasms/genetics , Germ-Line Mutation , Pheochromocytoma/genetics , Proto-Oncogene Proteins c-ret/genetics , Adrenal Gland Neoplasms/diagnosis , Adrenal Gland Neoplasms/urine , Adrenalectomy , Carcinoma, Medullary/genetics , Carcinoma, Medullary/surgery , Carcinoma, Medullary/urine , DNA Mutational Analysis , Exons , Female , Humans , Male , Metanephrine/urine , Middle Aged , Neoplasms, Multiple Primary/genetics , Neoplasms, Multiple Primary/surgery , Neoplasms, Multiple Primary/urine , Pedigree , Pheochromocytoma/diagnosis , Pheochromocytoma/urine , Proto-Oncogene Mas , Thyroid Neoplasms/genetics , Thyroid Neoplasms/surgery , Thyroid Neoplasms/urine , Thyroidectomy , Tomography, X-Ray Computed
19.
Cir. Esp. (Ed. impr.) ; 77(2): 70-74, feb. 2005. ilus, tab
Article Es | IBECS | ID: ibc-037728

Introducción. Desde hace un año hemos sustituido la laparotomía por la laparoscopia para realizar la fase abdominal de la cirugía del cáncer de esófago. Presentamos nuestra experiencia con la introducción de la cirugía videoasistida en el tratamiento quirúrgico del cáncer de esófago. Pacientes y método. Aportamos nuestra experiencia con 9 pacientes diagnosticados de cáncer de esófago. En 7 la laparoscopia estuvo precedida de una toracotomía derecha y una disección esofágica. Mediante una cervicotomía lateral izquierda se extrajo la pieza y se elaboró la anastomosis. En otros 2 pacientes, la laparoscopia fue previa y la técnica de Ibor Lewis se completó mediante toracotomía derecha. Resultados. Los resultados son aún poco valorables, dado el reducido número de pacientes operados. La morbilidad se sitúa en el 38,3%. La duración media de la intervención efectuada por laparoscopia se fija en 4 h y 50 min. Constatamos unos valores reducidos en requerimientos de sangre perioperatoria, complicaciones postoperatorias, analgesia y estancia hospitalaria. Conclusiones. La esofagectomía mínimamente invasiva puede ser realizada de una manera tan segura como la convencional y tiene grandes ventajas perioperatorias. La introducción de la laparoscopia representa para nosotros un primer paso para llegar a un procedimiento videoasistido en todas sus fases (AU)


Introduction. For the last year we have substituted laparotomy with laparoscopy for the abdominal stage of esophageal cancer surgery. We report our experience of the introduction of video-assisted surgery in the treatment of esophageal cancer. Patients and method. We report our experience of nine patients diagnosed with esophageal cancer. In seven patients laparoscopy was preceded by right thoracotomy and esophageal dissection. Then, a left anterolateral cervicotomy was performed to remove the specimen and to construct the esophagogastroanastomosis. In two patients the laparoscopic technique was performed first and the Ivor Lewis procedure was completed by right thoracotomy. Results. Due to the reduced number of operated patients, the results are of little significance. Morbidity was 38.3%. The mean duration of the surgical procedure in laparoscopic patients was 4h 50min. However, perioperative blood loss, postoperative complications, analgesic requirements and mean length of hospital stay were reduced. Conclusions. Video-assisted esophagectomy can be performed as safely as conventional esophagectomy and has considerable perioperative advantages. The introduction of the laparoscopic procedure is the first step in using video-assisted surgery at all stages of esophageal cancer surgery (AU)


Male , Female , Adult , Middle Aged , Humans , Video-Assisted Surgery/methods , Thoracotomy/methods , Laparoscopy , Esophagectomy/methods , Minimally Invasive Surgical Procedures/methods , Carcinoma, Squamous Cell/complications , Carcinoma, Squamous Cell/diagnosis , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/surgery , Anastomosis, Surgical/methods , Carcinoma/complications , Carcinoma/diagnosis , Carcinoma/surgery , Adenocarcinoma/diagnosis , Adenocarcinoma/surgery , Neoplasm Metastasis/diagnosis
20.
Gastroenterol Hepatol ; 27(9): 529-34, 2004 Nov.
Article Es | MEDLINE | ID: mdl-15544739

Accidental ingestion of foreign bodies is fairly common in the general population. However, recurrent, deliberate ingestion of foreign bodies associated with continual abdominal self-mutilation with blunt objects is extremely unusual. We present the case of a young woman with an underlying psychiatric disorder who repeatedly presented to the emergency department of our hospital for attempted suicide. The most frequent reason for presenting to the emergency department was ingestion of multiple objects, usually sharp metal objects, frequently associated with abdominal self-mutilation using a sharp instrument. Treatment consisted of extraction of the foreign bodies through upper gastrointestinal endoscopy or abdominal surgery. The patient has survived all these attempts with minimal morbidity.


Abdominal Injuries/etiology , Foreign Bodies/complications , Mental Disorders/complications , Suicide, Attempted , Abdominal Injuries/diagnostic imaging , Abdominal Injuries/surgery , Adult , Female , Foreign Bodies/diagnostic imaging , Gastroscopy , Humans , Laparotomy , Radiography, Abdominal , Self Mutilation/complications , Self Mutilation/diagnostic imaging , Treatment Outcome
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