CIDEC/FSP27 and PLIN1 gene expression run in parallel to mitochondrial genes in human adipose tissue, both increasing after weight loss.

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.

Inflammation and insulin resistance exert dual effects on adipose tissue tumor protein 53 expression.

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.

The lung innate immune gene surfactant protein-D is expressed in adipose tissue and linked to obesity status.

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.

Type I iodothyronine 5'-deiodinase mRNA and activity is increased in adipose tissue of obese subjects.

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.

Surgically treated perforations of the gastrointestinal tract caused by ingested foreign bodies.

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.

Obturator hernia: clinical analysis of 16 cases and algorithm for its diagnosis and treatment.

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.

Seat belt-induced intestinal perforation.

OBJECTIVE: To determine whether a relationship exists between bowel perforation and seat belt use in patients presenting abdominal trauma after traffic accidents. EXPERIMENTAL DESIGN: We prospectively studied every patient admitted to the emergency room with abdominal trauma after a traffic accident. PATIENTS AND METHODS: We included every patient diagnosed (clinically, by ultrasound or computerized tomography or at laparotomy) as suffering intraabdominal injury. The degree of trauma was classified according to the Injury Severity Score, taking into account the number of abdominal injuries associated with mortality and seat belt use. RESULTS: A total of 146 patients were studied. The spleen was the most frequently injured organ (n = 56). The mean Injury Severity Score was 19. Head injuries were more common among patients not wearing the seat belt. Thirteen cases of bowel perforation in patients who had been using the seat belt (p < 0.0001) were observed. CONCLUSION: Seat belt use can decrease the mortality rate associated with traffic accidents. However, a significant increase exists in the incidence of bowel perforations among seat belt wearers, probably as a result of improper use.

Thoracic esophageal perforations: surgical management with mechanical bipolar exclusion.

We report 12 cases of thoracic esophageal perforation diagnosed during the last seven years. Management was nonsurgical in 2 patients and the rest were treated surgically. Primary repair and drainage were performed in 2 patients, and 7 patients underwent suture of the perforation and bipolar exclusion using nonresorbable staples. The remaining patient was treated with proximal unipolar exclusion. The approach was always through a posterolateral thoracotomy. The result was optimal in 8 patients; the most important postsurgical complications were 2 esophageal fistulas that required surgery, and only one of the patients died of fulminating sepsis. Bipolar exclusion is a procedure that needs only one operation and provides excellent morbidity-mortality rates compared with other exclusion techniques with later reconstruction. We consider suturing with nonresorbable staples to be a simple and safe procedure, with spontaneous recanalization of the esophageal lumen in 2 weeks.

[Diaphragmatic hernia of Morgagni-Larrey in adults: analysis of 10 cases]. / Hernia diafragmática de Morgagni-Larrey en el adulto: análisis de 10 casos.

Congenital diaphragmatic hernia of Morgagni-Larrey is a rare entity that usually presents on the right side. These hernias, occurring in the anterior midline through the sternocostal hiatus of the diaphragm, are usually discovered incidentally when the patient has reached adulthood, or when they become symptomatic due to intestinal involvement (occlusive symptoms) or when respiratory dysfunction occurs. We present 10 patients (mean age: 69 years) with symptomatic sternocostal hernia and intestinal occlusion. In 7 patients, the hernia was located on the right (Morgagni's hernia) and in three it was located on the left (Larrey's hernia). Most of the patients presented important associated comorbidity, mainly cardiovascular and neoplastic. Surgical treatment consisted of reduction of the contents of the herniated sac and hernia repair through simple suture with or without mesh for reinforcement, mainly through the abdominal approach. Mortality in this series was nil. The infrequency of this entity and its diagnosis mainly in adults, with a high prevalence of circumstances favoring abdominal hernias, suggest that an embryological defect of the sternocostal foramina of Morgagni or Larrey are an essential element in the physiopathology of these processes.

[Gallstone Ileus: results of analysis of a series of 40 patients]. / Ileo biliar: resultados del análisis de una serie de 40 casos.

Gallstone ileus is an infrequent surgical emergency that nevertheless represents a not insignificant percentage of occlusions of the small intestine without strangulation. We present a retrospective study of 21 years (1980-2000) in 40 patients. Mean age was 76 years and most of the patients (85%) were women. Mean age and associated disease increased throughout the study period. Cases of gallstone ileus decreased in the second and third 5-year periods and clearly increased in the fourth (1996-2000). Localization of gallstones was ileum in 25 patients, jejunum in 9, duodenum in 3, colon in 1 and feces in 2. Only 12 patients (30%) received a correct preoperative diagnosis. Treatment was surgical in 38 patients with 7.5% mortality and 57.5% morbidity. Enterolithotomy was the technique of choice. A high degree of suspicion for gallstone ileus and early treatment may be the factors required to improve prognosis. The increase in life expectancy and associated comorbidity, which contraindicate elective surgery for cholelithiasis, may be contributing towards an increase in the population prone to developing gallstone ileus.

[Recurrent ingestion of foreign bodies and abdominal self-injury as a form of attempted suicide]. / Ingestión reiterada de cuerpos extraños y autoagresiones abdominales como intento de suicidio.

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.

Management of foreign bodies in the rectum.

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.