The effect of pegylated recombinant human leptin (PEG-OB) on weight loss and inflammatory status in obese subjects

The effect of pegylated recombinant human leptin (PEG-OB) on weight loss and inflammatory status in obese subjects. Hukshorn CJ, van Dielen FM, Buurman WA, Westerterp-Plantenga MS, Campfield LA, Saris WH. Nutrition and Toxicology Research Institute Maastricht, Department of Human Biology, Maastricht University, The Netherlands. [email protected] OBJECTIVE: To investigate whether weekly subcutaneous administration of 60 mg of long-acting pegylated human leptin (PEG-OB) for 8 weeks was able to influence weight loss, metabolic profile and inflammatory status of obese subjects on a mildly hypoenergetic diet (deficit: 3.2 MJ/day). DESIGN: A prospective, randomized, double-blind and placebo-controlled single-center trial. SUBJECTS: Twenty-eight healthy, obese subjects (16 women, 12 men; age 22-65 y; body mass index 27.7-38.7 kg/m2). MEASUREMENTS: Bodyweight, metabolic profile (including lipids), C-reactive protein (CRP) and soluble TNF alpha-receptor (sTNF-R) 55 and 75 levels. RESULTS: At the end of the study no significant differences in the delta or percentage weight loss between the placebo (n = 14) and PEG-OB (n = 14) groups was observed. Also the changes in metabolic profile, CRP, sTNF-R55 and R75 concentrations between the two groups after 8 weeks of treatment did not differ. CONCLUSION: Weekly injection of 60 mg PEG-OB did not lead to additional weight loss after 8 weeks of treatment. Furthermore, PEG-OB administration did not affect the changes in metabolic profile and the inflammatory status of obese subjects

Social Change and Betty Friedan's The Feminine Mystique: A Study of the Charismatic Author-Leader

In this thesis I explore the significance of the publication of Betty Friedan's The Feminine Mystique (1963) to the emergence of the second wave Women's Liberation Movement in the US in the late 1960s. To this end, I deploy key concepts provided through social movement theory (eg collective identity, collective action frames, social problem construction). I also incorporate Max Weber and Antonio Gramsci's insights on the indispensable role played by leaders who demonstrate a clear and effective political will. Weber's three part model of pure charisma is used as a general template for understanding the impact of Friedan's text. I critique aspects of Weber's theory of charisma, in particular his failure to appreciate that the written word can mark the initial emergence phase of charisma rather than its routinisation. I augment Weber's insights on charismatic leadership by attending to Gramsci's emphasis on the necessity of winning the 'war of ideas' that must be waged at the level of civil society within advanced capitalist societies. I examine Gramsci's understanding of the power available to the organic intellectual who is aligned with the interests of subaltern groups and who succeeds in revealing the hegemonic commitments of accepted 'common sense'. In the latter part of this thesis, I apply these many useful concepts to my case study analysis of Betty Friedan's The Feminine Mystique. I argue that Friedan's accessible, middlebrow text gave birth to a new discursive politics which was critically important not only for older women, but for a younger generation of more radicalised women. I emphasise how Friedan's text mounted a concerted attack on the discursive construction of femininity under patriarchal capitalism. I question Friedan's diagnostic claim that the problems American women faced were adequately captured by the terminology of the trapped housewife syndrome. I conclude by arguing that social movement researchers have to date failed to appreciate the leadership potential of the charismatic author-leader who succeeds in addressing and offering a solution to a pressing social problem through the medium of a best-selling, middlebrow text

Conversion of Vertical Banded Gastroplasty to Roux-en-Y Gastric Bypass Results in Restoration of the Positive Effect on Weight Loss and Co-morbidities: Evaluation of 101 Patients

BACKGROUND: Vertical banded gastroplasty (VBG) is a widely used restrictive procedure in bariatric surgery. However, the re-operation rate after this operation is high. In the case of VBG failure, a conversion to Roux-en-Y gastric bypass (RYGBP) is an option. A study was undertaken to evaluate the results of the conversion from VBG to RYGBP. METHODS: 101 patients had conversion from VBG to RYGBP. Patients were separated into 3 groups, based on the indication for conversion: weight regain (group 1), excessive weight loss (group 2) and severe eating difficulties (group 3). Data for the study were collected by retrospective analysis of prospectively recorded data. RESULTS: Weight regain (group 1) was the reason for conversion in 73.3% of patients. Staple-line disruption was the most important cause for the weight regain (74.3%). Excessive weight loss (group 2) affected 14% of patients and was caused by outlet stenosis in 78.6% of patients. The remaining 13% had severe eating difficulties as a result of outlet stenosis (46.1%), pouch dilatation (30.8%) and pouch diverticula (23.1%). Mean BMI before conversion to RYGBP was 40.5, 22.3 and 29.8 kg/m2 in group 1, 2 and 3, respectively. Minor or major direct postoperative complications were observed in 2.0% to 7.0%. Long-term complications were more frequent, and consisted mainly of anastomotic stenosis (22.7%) and incisional hernia (16.8%). Follow-up after conversion was achieved in all patients (100%), with a mean period of 38 +/- 29 months. BMI decreased from 40.5 to 30.1 kg/m2, increased from 22.3 to 25.3 kg/m2. and decreased slightly from 29.8 to 29.0 kg/m2 in group 1, 2 and 3, respectively. All patients in group 3 noticed an improvement in eating difficulties. CONCLUSION: Complications after conversion from failed VBG to RYGBP are substantial and need to be considered. However, the conversion itself is a successful operation in terms of effect on body weight and treating eating difficulties after VBG

Effect of axillary brachial plexus blockade on baroreflex-induced skin vasomotor responses: Assessing the effectiveness of sympathetic blockade

Background: The combination of laser Doppler flowmetry and non-invasive blood pressure monitoring allows the continuous observation of cutaneous vascular resistance (CVR). Continuous recording of unmodulated skin blood flow (SBF) is very sensitive to artefacts, rendering the method unreliable. In contrast, intermittent short lasting challenges of the CVR by cardiovascular autonomic reflexes may provide information about the responsiveness of the sympathetic nervous system in the skin. Methods: Eleven patients with below-wrist hand surgery (six males and five females; aged 35.2 ± 7.1 years) performed Valsalva maneuver following axillary blockade. Skin blood flow was continuously monitored on the forearm of the side axillary blockade, as well as on the contra-lateral forearm, which was used as the control. The responses were expressed as changes compared with the baseline level derived from a resting period of 30s. The maxima

Co-expressed immune and metabolic genes in visceral and subcutaneous adipose tissue from severely obese individuals are associated with plasma HDL and glucose levels: a microarray study

<p>Abstract</p> <p>Background</p> <p>Excessive accumulation of body fat, in particular in the visceral fat depot, is a major risk factor to develop a variety of diseases such as type 2 diabetes. The mechanisms underlying the increased risk of obese individuals to develop co-morbid diseases are largely unclear.</p> <p>We aimed to identify genes expressed in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) that are related to blood parameters involved in obesity co-morbidity, such as plasma lipid and glucose levels, and to compare gene expression between the fat depots.</p> <p>Methods</p> <p>Whole-transcriptome SAT and VAT gene expression levels were determined in 75 individuals with a BMI >35 kg/m². Modules of co-expressed genes likely to be functionally related were identified and correlated with BMI, plasma levels of glucose, insulin, HbA_1c, triglycerides, non-esterified fatty acids, ALAT, ASAT, C-reactive protein, and LDL- and HDL cholesterol.</p> <p>Results</p> <p>Of the approximately 70 modules identified in SAT and VAT, three SAT modules were inversely associated with plasma HDL-cholesterol levels, and a fourth module was inversely associated with both plasma glucose and plasma triglyceride levels (p < 5.33 × 10^-5). These modules were markedly enriched in immune and metabolic genes. In VAT, one module was associated with both BMI and insulin, and another with plasma glucose (p < 4.64 × 10^-5). This module was also enriched in inflammatory genes and showed a marked overlap in gene content with the SAT modules related to HDL. Several genes differentially expressed in SAT and VAT were identified.</p> <p>Conclusions</p> <p>In obese subjects, groups of co-expressed genes were identified that correlated with lipid and glucose metabolism parameters; they were enriched with immune genes. A number of genes were identified of which the expression in SAT correlated with plasma HDL cholesterol, while their expression in VAT correlated with plasma glucose. This underlines both the singular importance of these genes for lipid and glucose metabolism and the specific roles of these two fat depots in this respect.</p

Gender Dimorphism in Skeletal Muscle Leptin Receptors, Serum Leptin and Insulin Sensitivity

To determine if there is a gender dimorphism in the expression of leptin receptors (OB-R170, OB-R128 and OB-R98) and the protein suppressor of cytokine signaling 3 (SOCS3) in human skeletal muscle, the protein expression of OB-R, perilipin A, SOCS3 and alpha-tubulin was assessed by Western blot in muscle biopsies obtained from the m. vastus lateralis in thirty-four men (age = 27.1±6.8 yr) and thirty-three women (age = 26.7±6.7 yr). Basal serum insulin concentration and HOMA were similar in both genders. Serum leptin concentration was 3.4 times higher in women compared to men (P<0.05) and this difference remained significant after accounting for the differences in percentage of body fat or soluble leptin receptor. OB-R protein was 41% (OB-R170, P<0.05) and 163% (OB-R128, P<0.05) greater in women than men. There was no relationship between OB-R expression and the serum concentrations of leptin or 17β-estradiol. In men, muscle OB-R128 protein was inversely related to serum free testosterone. In women, OB-R98 and OB-R128 were inversely related to total serum testosterone concentration, and OB-R128 to serum free testosterone concentration. SOCS3 protein expression was similar in men and women and was not related to OB-R. In women, there was an inverse relationship between the logarithm of free testosterone and SCOS3 protein content in skeletal muscle (r = −0.46, P<0.05). In summary, there is a gender dimorphism in skeletal muscle leptin receptors expression, which can be partly explained by the influence of testosterone. SOCS3 expression in skeletal muscle is not up-regulated in women, despite very high serum leptin concentrations compared to men. The circulating form of the leptin receptor can not be used as a surrogate measure of the amount of leptin receptors expressed in skeletal muscles

Re-operation after laparoscopic adjustable gastric banding leads to a further decrease in BMI and obesity-related co-morbidities: results in 33 patients

BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) is a safe technique with few direct postoperative complications. However, long-term complications such as slippage and pouch dilatation are a well-known problem and re-operations are necessary in a substantial number of patients. In this study, the results of laparoscopic re-operations after LAGB are evaluated. METHODS: 33 patients had a re-operation because of failed LAGB. 29 patients had major re-operation and 4 patients minor re-operation under local anesthesia. The charts of these patients were retrospectively studied. RESULTS: Mean time between the first band placement and re-operation was 28.1 +/- 17.6 months. The cause of band dysfunction was anterior slippage (n=17), band erosion (n=5), band intolerance (n=3), posterior slippage (n=2) and band leakage (n=2). Symptoms of band dysfunction were vomiting (n=16), pyrosis (n=13), nausea (n=8), retrosternal pain (n=11) and regurgitation (n=5). Laparoscopic refixation of the band was performed in 19 patients: the band was replaced in 4 patients while in 1 patient the band was removed; in 3 patients, the laparoscopic procedure was converted to open surgery; 5 patients underwent conversion to a bypass procedure (biliopancreatic diversion in 3 and gastric bypass in 2). There were no direct postoperative complications except for wound infections (n=2). Postoperative follow-up was 100% with a mean period of 34 +/- 19 months. BMI decreased further from 37.5 +/- 6.4 kg/m(2) before re-operation to 33 +/- 7 kg/m(2). Obesity-related co-morbidity also decreased further or completely dissolved. 3 patients (9%) again developed anterior slippage and a second laparoscopic re-operation was necessary. CONCLUSIONS: A laparoscopic re-operation for band-related complications after LAGB is safe and feasible. With band slippage, a laparoscopic refixation was possible in 89%. Re-operation leads to further decrease in BMI and obesity-related co-morbidities