Bariatric surgery modulates plasma levels of antibodies against angiotensin II type 1 and endothelin 1 type A receptor in severe obesity.

PURPOSE: The contribution of endothelial-targeted autoantibodies against the angiotensin II type 1 receptor (anti-AT1R) and the anti-endothelin 1 type A receptor (anti-ETAR1) has been proposed in the development of cardiovascular diseases. However, no data have been reported yet in obesity. In this observational study we evaluated the relationship between anthropometric and metabolic parameters and anti-AT1R and anti-ETAR1 concentrations in a cohort of patients with severe obesity and associated comorbidities undergoing bariatric surgery. METHODS: Clinical evaluation and metabolic assessment were performed in 36 subjects referring to our Center for the Study and Integrated Treatment of Obesity at the University Hospital of Padova. Circulating inflammatory adipocytokines and the endothelial dysfunction marker asymmetric dimethylarginine (ADMA) were evaluated; plasma levels of anti-AT1R and anti-ETAR1 were also determined. 10 normal-weight subjects were considered as a control group. 29 patients out of 36 were re-evaluated after surgery. RESULTS: With respect to normal-weight controls patients showed significantly higher plasma levels of anti-AT1R (28 ± 20.4 vs 13.5 ± 2.8 U/mL, p < 0.005) and ADMA (0.8 ± 0.1 vs 0.54 ± 0.08 uM/L, p < 0.0001) but not anti-ETAR1 (14.2 ± 1.3 vs 13.3 ± 2 U/mL, p = 0.1). Anti-AT1R concentration showed an increasing trend with the worsening of glycemic status, while the presence of arterial hypertension among the patients did not affect autoantibodies levels. One year after surgery, a significant improvement in body weight and metabolic and inflammatory parameters was observed, along with a significant reduction of anti-AT1R (28.1 ± 20.4 U/mL vs 22.6 ± 16 U/mL, p < 0.05) and anti-ETAR1 (14.2 ± 1.3 U/L vs 13 ± 1.6 U/L, p < 0.01). CONCLUSIONS: Subjects with obesity present higher plasma levels of anti-AT1R which are more related to glycemic profile than blood pressure levels, and are reduced by bariatric surgery. Considering the detrimental effects of these autoantibodies on vascular health, they should be assessed as potential biomarkers in obesity and metabolic diseases.

Treatment with dapagliflozin increases FGF-21 gene expression and reduces triglycerides content in myocardial tissue of genetically obese mice.

BACKGROUND: The association between obesity and some cardiovascular complications such as heart failure (HF) is well established, and drugs affecting adiposity are supposed to be promising treatments for these conditions. The sodium-glucose cotransporter-2 inhibitors (SGLT2i) are antidiabetic drugs showing benefits in patients with HF, despite the underlying mechanisms have not been completely understood yet. SGLT2i are supposed to promote systemic effects, such as triglycerides mobilization, through the enhancement of fibroblast growth factor-21 (FGF-21) activity. So, in this study, we evaluated the effects of dapagliflozin treatment on FGF-21 and related receptors (FGF-Rs) gene expression and on lipid content in myocardial tissue in an animal model of genetically induced obesity to unravel possible metabolic mechanisms accounting for the cardioprotection of SGLT2i. METHODS: Six-week-old C57BL/6J wild-type mice and B6.V-LEP (ob/ob) mice were randomly assigned to the control or treatment group (14 animals/group). Treatment was based on the administration of dapagliflozin 0.15 mg/kg/day for 4 weeks. The gene expression of FGF-21 and related receptors (FGF-R1, FGF-R3, FGF-R4, and ß-klotho co-receptor) was assessed at baseline and after treatment by real-time PCR. Similarly, cardiac triglycerides concentration was measured in the control group and treated animals. RESULTS: At baseline, FGF-21 mRNA expression in the heart did not differ between lean and obese ob/ob mice. Dapagliflozin administration significantly increased heart FGF-21 gene expression, but only in ob/ob mice (p < 0.005). Consistently, when measuring the amount of triglycerides in the cardiac tissue, SGLT2i treatment reduced the lipid content in obese ob/ob mice, while no significant effects were observed in treated lean animals (p < 0.001). The overall expression of the FGF-21 receptors was only minimally affected by dapagliflozin treatment both in obese ob/ob mice and in lean controls. CONCLUSIONS: Dapagliflozin administration increases FGF-21gene expression and reduces triglyceride content in myocardial tissue of ob/ob mice, while no significant effect was observed in lean controls. These results might help understand the cardiometabolic effects of SGLT2i inducing increased FGF-21 synthesis while reducing lipid content in cardiomyocytes as a possible expression of the switch to different energy substrates. This mechanism could represent a potential target of SGLT2i in obesity-related heart diseases.

Effects of environmental concentrations of the fragrance amyl salicylate on the mediterranean mussel Mytilus galloprovincialis.

Amyl salicylate (AS) is a fragrance massively used as a personal care product and following the discharged in wastewaters may end up in the aquatic environment representing a potential threat for the ecosystem and living organisms. AS was recently detected in water of the Venice Lagoon, a vulnerable area continuously subjected to the income of anthropogenic chemicals. The lagoon is a relevant area for mollusc farming, including the Mediterranean mussels (Mytilus galloprovincialis) having an important economic and ecological role. Despite high levels of AS occurred in water of the Lagoon of Venice, no studies investigated the possible consequences of AS exposures on species inhabiting this ecosystem to date. For the first time, we applied a multidisciplinary approach to investigate the potential effects of the fragrance AS on Mediterranean mussels. To reach such a goal, bioaccumulation, cellular, biochemical, and molecular analyses (RNA-seq and microbiota characterization) were measured in mussels treated for 7 and 14 days with different AS Venice lagoon environmental levels (0.1 and 0.5 µg L-1). Despite chemical investigations suggested low AS bioaccumulation capability, cellular and molecular analyses highlighted the disruption of several key cellular processes after the prolonged exposures to the high AS concentration. Among them, potential immunotoxicity and changes in transcriptional regulation of pathways involved in energy metabolism, stress response, apoptosis and cell death regulations have been observed. Conversely, exposure to the low AS concentration demonstrated weak transcriptional changes and transient increased representation of opportunistic pathogens, as Arcobacter genus and Vibrio aestuarianus. Summarizing, this study provides the first overview on the effects of AS on one of the most widely farmed mollusk species.

Lake sediment fecal and biomass burning biomarkers provide direct evidence for prehistoric human-lit fires in New Zealand.

Deforestation associated with the initial settlement of New Zealand is a dramatic example of how humans can alter landscapes through fire. However, evidence linking early human presence and land-cover change is inferential in most continental sites. We employed a multi-proxy approach to reconstruct anthropogenic land use in New Zealand's South Island over the last millennium using fecal and plant sterols as indicators of human activity and monosaccharide anhydrides, polycyclic aromatic hydrocarbons, charcoal and pollen as tracers of fire and vegetation change in lake-sediment cores. Our data provide a direct record of local human presence in Lake Kirkpatrick and Lake Diamond watersheds at the time of deforestation and a new and stronger case of human agency linked with forest clearance. The first detection of human presence matches charcoal and biomarker evidence for initial burning at c. AD 1350. Sterols decreased shortly after to values suggesting the sporadic presence of people and then rose to unprecedented levels after the European settlement. Our results confirm that initial human arrival in New Zealand was associated with brief and intense burning activities. Testing our approach in a context of well-established fire history provides a new tool for understanding cause-effect relationships in more complex continental reconstructions.

The impact of the 1999 Mw 7.4 event in the Izmit Bay (Turkey) on anthropogenic contaminant (PCBs, PAHs and PBDEs) concentrations recorded in a deep sediment core.

The 1999 Mw 7.4 earthquake triggered a tremendous human tragedy and had a great social impact over the population of the Izmit Bay, one of the most industrialized area of Turkey. Although the successive environmental disasters were well documented, information on its sedimentary record is lacking. The present research aims at filling this gap, through the analysis of organic contaminants (PCBs, PAHs, and PBDEs) in a dated sediment core collected in the depocenter of the Karamürsel Basin in 2005. Profiles of total PCBs and total PAHs overlap the timing of industrialization in the area (starting in the 1960s) with values increasing as the population and the number of industrial plants grew larger. Profiles for PBDEs are in accordance with increasing urban inputs but are probably affected by processes of natural formation and post-depositional mixing. The continuous sedimentary record is interrupted at a level dating back to 1980 due to the erosion caused by the 1999 earthquake, having removed a 5-7cm thick sediment layer. Contaminant concentrations in the deepest 10-15cm of a 30cm thick seismo-turbidite unit, triggered by the 1999 event, increase with the progressive fining up and evidence massive transport of sediments from coastal, more polluted sites of the north-eastern Karamürsel shelves and shores. Additional inputs of PAHs are also evident, originating from a fire at the oil refinery that followed the shaking. The effects of the earthquake generated tsunami, its backwash fluxes and the following seiches are not uniquely displayed by each class of contaminants, and they could probably reflect successive inputs deriving from different parts of the basin that are subject to anthropogenic impacts of different nature. Concentrations measured at the top of the core are consistent with an unvaried input of pollutants in the period 1980-2005.

Exploring the possibility to detect recent temporal changes in highly disturbed sedimentary records through sampling repetitions and core comparisons of porosity and sand content.

Dating of sediment cores in dynamic environments (such as tropical coastal lagoons) is often impossible to achieve, due to the difficulty to recover continuous and undisturbed records. Detailed temporal definition of environmental changes cannot be assured, but there is the possibility that information retained in such sediments can still provide useful insights on local or large-scale sedimentary dynamics, when a specific strategy is adopted. This latter consists in repeated core samplings at the same location and in the comparison of core profiles for basic and easily measurable parameters (porosity and sand content). This approach was tested on sediment cores, collected repeatedly during the period 2005-2010, at the same site of the Thi Nai Lagoon (central Vietnam). The proposed procedure was able to evidence the impact on lagoon sediments of activities linked to the construction of industrial settlements in the area, with dredging removing a consistent sediment layer from 2005 to 2008 and waste dumping providing additional sediment input in the following period. Simple statistic confirmed this scenario, together with core profiles of PCBs, As, Cd, Pb, and Zn. The procedure represents a simple tool to study coastal dynamics in places where the level of accuracy of traditional sediment radiodating cannot be reached. Several ameliorations are suggested in order to help developing the monitoring of sedimentary processes in poorly studied areas.

Development of a method for simultaneous analysis of PCDDs, PCDFs, PCBs, PBDEs, PCNs and PAHs in Antarctic air.

The development of a unique analytical method for the determination of five classes of persistent organic pollutants (POPs) in atmospheric gas and the particle phase through gas chromatography coupled to high-resolution mass spectrometry is presented. Every step of the pre-analytical and analytical optimization process is described. Great effort was put into simplifying the traditional techniques, with reference to EPA and literature methods. Automated instruments were used for sample extraction and cleanup in order to enhance repeatability and reduce contamination risks. Unlike most common approaches, no separation of the analytes was performed before the GC analysis in order to avoid sample fractionation and to save time and materials. This allowed low instrumental and method detection limits (pg to sub-pg) to be achieved. Accuracy and precision were tested by fortifying the matrix and analysing standard reference materials (NIST SRM 1649b Urban Dust and 2585 Organic Contaminants in House Dust). The method was applied to five samples from Terra Nova Bay, Antarctica. Concentrations of polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs), polychlorinated biphenyls (PCBs), polychlorinated naphthalenes (PCNs), polybrominated diphenyl ethers (PBDEs) and polycyclic aromatic hydrocarbons (PAHs) are presented. Lighter compounds dominate the distribution and are mainly present in the gaseous phase. The observed pattern may be attributable to long-range transport. Results are in general agreement with literature data, where available.

Risk factors for colorectal anastomotic stenoses and their impact on quality of life: what are the lessons to learn?

AIM: The aim of the study was to analyse the incidence of benign colorectal anastomotic stenoses in consecutive patients operated on in a single institution and to assess risk factors for their development. Their impact on quality of life was also evaluated. METHOD: Patient characteristics, indications for surgery, surgical technique and postoperative complications were prospectively recorded. Stenosis was evaluated by rectoscopy at regular intervals, and patients were treated only if symptomatic. After at least 6 months following surgery, patients were asked to respond to the Short Form 36-item quality-of-life questionnaire during a telephone interview. RESULTS: Of the original 211 patients considered, 195 underwent a follow-up rectoscopy and were included in the study. Benign stenosis were found in 26 (13%), and 19 (73%) symptomatic patients were treated successfully (15 with endoscopic dilatation and four with radial diathermic surgical incisions). Risk factors for anastomotic stenosis according to univariate analysis were female sex, diverticulitis, mechanical anastomosis, and anastomosis located between 8 and 12 cm from the anal verge. The significant risk factors identified by multivariate analysis were diverticulitis (OR 5, P=0.002) and mechanical anastomosis (OR 9, P=0.04). The self-perceived quality of life of patients with stenosis was significantly worse compared with controls. CONCLUSION: Since diverticulitis and mechanical anastomosis are risk factors for anastomotic stenosis, surgeons should take this into account when they are considering what type of anastomotic technique to utilize.

Subclinical myopathy in patients affected with newly diagnosed colorectal cancer at clinical onset of disease: evidence from skeletal muscle biopsies.

OBJECTIVE: To evaluate skeletal muscle biopsy from asymptomatic patients affected with newly diagnosed colorectal cancer and to identify pathological features which may be indicative of tumor-associated muscle disorders, potentially leading to cachexia. METHODS: Patients affected with newly diagnosed colorectal cancer at clinical onset of disease underwent biopsy of the rectus abdominis muscle during elective laparoscopic tumor resection, before chemotherapeutic treatment. Morphometric analyses, ATPase histochemistry and immunohistochemical studies using antibodies directed to N-CAM and to MHC-emb, two sound makers of muscle denervation and injury-induced muscle regeneration, were performed on intraoperative muscle biopsies from ten patients. Muscle biopsies from rectus abdominis of seven subjects affected with non-neoplastic condition, which underwent laparoscopic surgery, were used as controls. RESULTS: In patients' biopsies, we observed a surprisingly high percentage of myofibers with internalized or central nuclei compared to controls (9.15 +/- 8.9 versus 0.6 +/- 0.9, p<0.0003). In addition, in the 30% of patients, small myofibers expressing the MHC-emb have been identified (0.4 +/- 0.5 positive fibers/mm(2)), while in 50% of patients, larger fibers positive for N-CAM have also been detected (0.7 +/- 1.1 positive fibers/mm(2)), suggesting that investigated muscle biopsies exhibit other evidence of muscle fiber injury/regeneration and/or denervation. Among the 10,000 analysed myofibers in control biopsies, no MHC-emb and N-CAM-positive muscle fibers have been detected. Thus, patients affected with newly diagnosed colorectal cancer at clinical onset of disease display early signs of a subclinical myopathy. DISCUSSION: Factors and mechanisms of this cancer-associated myopathy are yet unknown. The facts that the great majority of the abnormally nucleated myofibers are of the fast type and that regenerating myofibers are present, suggest a myogenic response to the colorectal cancer and not to the laparoscopic modalities of the biopsy harvesting. Follow-up of the patients will elucidate the clinical relevance of our observation, and further studies investigating the molecular mechanism underlying this early cancer-associated myopathy will hopefully provide some pathogenetic clues leading to the identification of potential specific targets for therapeutic intervention to prevent tumor cachexia.

Polymyositis, dermatomyositis and malignancy: a further intriguing link.

The association between malignancy and autoimmune myositis has been largely described and confirmed by numerous epidemiological studies. The temporal relationship between the two pathologic conditions can vary: malignancy may occur before, at the same time or following the diagnosis of myositis. Beside these observations, the molecular mechanisms underlying this association are still unknown, even though it has been demonstrated a possible antigenic similarity between regenerating myoblasts and some cancer cell populations. To better identify peculiar histopathologic features common to cancer and myositis, we screened muscle biopsies from patients affected with polymyositis, dermatomyositis, myositis in association to cancer, and from patients affected with newly diagnosed cancer, but without myositis. Similarly to the histopatologic features that were observed in the muscle from myositis patients, especially in those with cancer associated myositis, in patients affected with malignancy at the clinical onset of disease we observed early sign of myopathy, characterized by internally nucleated and regenerating myofibers, most of them expressing the neural cell adhesion molecule. The hypothesis that in a particular subset of individuals genetically predisposed to autoimmunity, an initial subclinical tumor-induced myopathy may result in an autoimmune myositis, represents a further intriguing link behind the association of these two conditions.

Extensive anal condylomatosis: prognosis in relation to viral and host factors.

OBJECTIVE: To evaluate the clinical course of extensive anal condylomatosis in relation to treatment modalities, patient comorbidity and immune function, and associated papillomavirus (HPV) sequences. METHOD: Clinical data, treatment modalities and follow-up were recorded and analysed in relation to host and viral type. Histology, immunohistochemistry and molecular analyses for HPV search and typing were performed on formalin-fixed paraffin-embedded samples. RESULTS: Sixteen patients [14 males, median age 41.8 years (range 19-66)] affected by extensive anal condylomatosis [10 Buschke-Lowenstein Tumors (BLT) and 6 condylomatosis] treated in three different Italian institutions were included. There was associated preoperative anal intraepithelial neoplasia grade 3 (AIN3) in one and invasive carcinoma in three patients. After radical resection (n = 16) recurrence occurred in 4/10 (40%) BLT patients. Malignancy before or after treatment developed in 5/16 (31.25%) patients. HPV sequences were present in all the samples of 15 evaluable patients (types 6 or 11, 9 patients; type 16, 6 patients). A statistically significant association was found between presence of HPV type 16 and both malignancy and recurrence. Viral variant L83V was present in 3/4 HPV 16 positive recurrent cases. CONCLUSION: Radical resection resulted in a favourable clinical course. Typing of HPV sequences in the management of patients affected by extensive anal condylomatosis may be useful.

A new endoscopic technique for suspension of esophageal prosthesis for refractory caustic esophageal strictures.

There is no clear consensus concerning the best endoscopic treatment of benign refractory esophageal strictures due to caustic ingestion. Different procedures are currently used: frequent multiple dilations, retrievable self-expanding stent, nasogastric intubation and surgery. We describe a new technique to fix a suspended esophageal silicone prosthesis to the neck in benign esophageal strictures; this permits us to avoid the frequent risk of migration of the expandable metallic or plastic stents. Under general anesthesia a rigid esophagoscope was placed in the patient's hypopharynx. Using transillumination from the optical device, the patient's neck was pierced with a needle. A n.0 monofilament surgical wire was pushed into the needle, grasped by a standard foreign body forceps through the esophagoscope and pulled out of the mouth (as in percutaneous endoscopic gastrostomy procedure). After tying the proximal end of the silicone prosthesis with the wire, it was placed through the strictures under endoscopic view. This procedure was successfully utilized in four patients suffering from benign refractory esophageal strictures due to caustic ingestion. The prosthesis and its suspension from the neck were well-tolerated until removal (mean duration 4 months). A postoperative transitory myositis was diagnosed in only one patient. One of the most frequent complications of esophageal prostheses in refractory esophageal strictures due to caustic ingestion is distal migration. Different solutions were proposed. For example the suspension of a wire coming from the nose and then fixed behind the ear. This solution is not considered optimal because of patient complaints and moreover the aesthetic aspect is compromised. The procedure we utilized in four patients utilized the setting of a silicone tube hanging from the neck in a way similar to that of endoscopic pharyngostomy. This solution is a valid alternative both for quality of life and for functional results.

Colpocystodefecography in obstructed defecation: is it really useful to the surgeon? Correlating clinical and radiological findings in surgery for obstructed defecation.

OBJECTIVE: Colpocystodefecography images the pelvic floor with the dynamics of defecation, but various authors claim that it overestimates clinical findings. The aim of this study was to evaluate the pre- and postoperative consistency between clinical and colpocystodefecographic findings in patients undergoing surgery for obstructed defecation. METHOD Between June 2001 and September 2003, 20 patients underwent transvaginal posterior colpoperineorrhaphy and rectal mucosal prolapsectomy with one circular stapler for symptomatic rectocele and concomitant anorectal prolapse. They were prospectively evaluated both before surgery by designed questionnaire on constipation and incontinence, proctological, gynaecological and urological examinations, colpocystodefecography and anorectal manometry, and after operation at 6 months by questionnaire and a proctological check-up. The mean follow-up was 30 months (24-48 months). RESULTS: At 6 months the questionnaire revealed a major response in terms of symptoms. The proctological visit confirmed the absence of rectocele in 19 (95%) patients, while the anorectal prolapse had completely disappeared in 17 (85%) patients. Postoperative colpocystodefecography demonstrated a general reduction in the dimensions of the rectocele, which had completely disappeared in five (25%) patients; 40% of the patients had a persistent anorectal prolapse. CONCLUSION: Preoperative data analysis showed a statistically significant correlation between clinical and radiological findings. Postoperatively the global clinical assessment correlated well with patient satisfaction, while there was evidence of a statistically significant difference between the radiological and clinical findings. Routine postoperative use of colpocystodefecography is unjustified unless there is clinical evidence of surgical failure.

Prospective randomized study on perioperative enteral immunonutrition in laparoscopic colorectal surgery.

BACKGROUND: Perioperative nutrition for patients undergoing colon surgery seems to be effective in reducing catabolism and improving immunologic parameters. A relatively low-fiber and highly absorbable diet may facilitate the intestinal cleansing and loop relaxation fundamental for laparoscopic surgery with a lower dose of iso-osmotic laxative. METHODS: From 1 February 2004 to 30 July 2005, 28 patients referred to our unit with colon disease (neoplasms and diverticular disease) amenable to laparoscopic surgery were prospectively randomized into two groups of 14 patients each. For 6 days preoperatively, the patients in group 1 were given 750 ml/day of a diet enriched with arginine, omega-3 fatty acids, and ribonucleic acid (RNA) associated with low-fiber foods. They had 1 day of intestinal preparation with 3 l of iso-osmotic laxative. On postoperative day 2, they were fed orally with the same diet. The patients in group 2 preoperatively received a low-fiber diet. They had 2 days of preparation with iso-osmotic laxative (3 l/day). On postoperative day 3, oral nutrition was restored. Intraoperatively, we evaluated loop relaxation and intestinal cleanliness. Clinical trends were monitored in both groups, as well as adverse reactions to early nutrition. The nutritional (albumin, prealbumin) and immunologic (lymphocyte subpopulations, immunoglobulins) biohumoral parameters were evaluated at the first visit, on the day before surgery, on postoperative day 7, and 1 month after surgery. RESULTS: The two groups did not differ in terms of age, gender, distribution of disease, or baseline anthropometric, biohumoral, or immunologic parameters. There was a significant increase in CD4 lymphocytes on the day before surgery as compared with baseline parameters (p < 0.05) in group 1, but not in group 2. There was no statistically significant difference between the two groups in intestinal loop relaxation or cleanliness or in postoperative infectious complications. CONCLUSIONS: Perioperative immunonutrition proved to be safe and useful in increasing the perioperative immunologic cell response. It may contribute toward improving the preparation and relaxation of the intestinal loops despite the shorter intestinal preparation.

Early rupture of subclavian vein catheter: a case report and literature review.

Prolonged venous access devices (PVADs) have become indispensable in antiblastic protocols for the treatment of cancer patients, in anti-infection protocols for acquired immunodeficiency syndrome (AIDS) patients and in the management of chronic malabsorption syndromes. Using these catheters carries the risk of several complications, and some are potentially lethal, for example, cardiac embolization of catheter fragments. Rupture is a complication almost exclusive to catheters positioned percutaneously: after using this technique, device malfunction can occur due to catheter kinking after its excessively medial introduction in the subclavian vein. The early recognition of any pinch-off sign (POS) is fundamental in preventing catheter rupture that frequently follows this complication. Other factors can be involved in early rupture, for example, excessive force on a syringe used to clear a catheter that shows early signs of malfunction, or a strength defect in the materials used in the catheter construction. This report describes an early rupture case of an initially correctly positioned catheter and reviews 20 such cases in the recent literature.