The worldwide epidemic of obesity has brought considerable attention to research aimed at understanding the biology of adipocytes (fat cells) and the events occurring in adipose tissue (fat) and in the bodies of obese individuals. Accumulating evidence indicates that obesity causes chronic low-grade inflammation and that this contributes to systemic metabolic dysfunction that is associated with obesity-linked disorders. Adipose tissue functions as a key endocrine organ by releasing multiple bioactive substances, known as adipose-derived secreted factors or adipokines, that have pro-inflammatory or anti-inflammatory activities. Dysregulated production or secretion of these adipokines owing to adipose tissue dysfunction can contribute to the pathogenesis of obesity-linked complications. In this Review, we focus on the role of adipokines in inflammatory responses and discuss their potential as regulators of metabolic function.

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Adipokines in inflammation and metabolic disease

Gas storage in solids is becoming an ever more important technology, with applications and potential applications ranging from energy and the environment all the way to biology and medicine. Very highly porous materials, such as zeolites, carbon materials, polymers, and metal-organic frameworks, offer a wide variety of chemical composition and structural architectures that are suitable for the adsorption and storage of many different gases, including hydrogen, methane, nitric oxide, and carbon dioxide. However, the challenges associated with designing materials to have sufficient adsorption capacity, controllable delivery rates, suitable lifetimes, and recharging characteristics are not trivial in many instances. The different chemistry associated with the various gases of interest makes it necessary to carefully match the properties of the porous material to the required application.

Gas Storage in Nanoporous Materials

A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease☆

Objective:To summarize the current world position on laparoscopic liver surgery.Summary Background Data:Multiple series have reported on the safety and efficacy of laparoscopic liver surgery. Small and medium sized procedures have become commonplace in many centers, while major laparoscopic liver re

The international position on laparoscopic liver surgery: The Louisville Statement, 2008.

Purpose: The goal of this retrospective analysis was to assess how well predictive models could determine which patients would develop liver chemistry signals during clinical trials based on their pretreatment (baseline) information. Patients and methods: Based on data from 24 late-stage clinical trials, classification models were developed to predict liver chemistry outcomes using baseline information, which included demographics, medical history, concomitant medications, and baseline laboratory results. Results: Predictive models using baseline data predicted which patients would develop liver signals during the trials with average validation accuracy around 80%. Baseline levels of individual liver chemistry tests were most important for predicting their own elevations during the trials. High bilirubin levels at baseline were not uncommon and were associated with a high risk of developing biochemical Hy’s law cases. Baseline γ-glutamyltransferase (GGT) level appeared to have some predictive value, but did not increase predictability beyond using established liver chemistry tests. Conclusion: It is possible to predict which patients are at a higher risk of developing liver chemistry signals using pretreatment (baseline) data. Derived knowledge from such predictions may allow proactive and targeted risk management, and the type of analysis described here could help determine whether new biomarkers offer improved performance over established ones.

/pdf/drug-design-development-and-therapy-15ijgzbk7u.pdf

Drug Design, Development and Therapy

Effect of waiting time on renal transplant outcome

Adipose tissue depots originate from distinct precursor cells, are functionally diverse, and modulate disease processes in a depot-specific manner. However, the functional properties of perivascular adipocytes, and their influence on disease of the blood vessel wall, remain to be determined. We show that human coronary perivascular adipocytes exhibit a reduced state of adipocytic differentiation as compared with adipocytes derived from subcutaneous and visceral (perirenal) adipose depots. Secretion of antiinflammatory adiponectin is markedly reduced, whereas that of proinflammatory cytokines interleukin-6, interleukin-8, and monocyte chemoattractant protein-1, is markedly increased in perivascular adipocytes. These depot-specific differences in adipocyte function are demonstrable in both freshly isolated adipose tissues and in vitro-differentiated adipocytes. Murine aortic arch perivascular adipose tissues likewise express lower levels of adipocyte-associated genes as compared with subcutaneous and visceral adipose tissues. Moreover, 2 weeks of high-fat feeding caused further reductions in adipocyte-associated gene expression, while upregulating proinflammatory gene expression, in perivascular adipose tissues. These changes were observed in the absence of macrophage recruitment to the perivascular adipose depot. We conclude that perivascular adipocytes exhibit reduced differentiation and a heightened proinflammatory state, properties that are intrinsic to the adipocytes residing in this depot. Dysfunction of perivascular adipose tissue induced by fat feeding suggests that this unique adipose depot is capable of linking metabolic signals to inflammation in the blood vessel wall.

Proinflammatory Phenotype of Perivascular Adipocytes: Influence of High-Fat Feeding

Objective:To evaluate our experience with more than 500 minimally invasive hepatic procedures.Summary Background Data:Recent data have confirmed the safety and efficacy of minimally invasive liver surgery. Despite these reports, no programmatic approach to minimally invasive liver surgery has been p

Experience With More Than 500 Minimally Invasive Hepatic Procedures

How to represent a graph in memory is a fundamental data structuring question. In the usual representations of an n-vertex graph, the names of the vertices (i.e., integers from 1 to n) betray nothing about the graph itself. Indeed, the names (or labels) on the n vertices are just $\log n$ bit place holders to allow data on the edges to encode the structure of the graph. In this scenario, there is no such waste. By assigning $O(\log n)$ bit labels to the vertices, the structure of the graph is completely encoded, so that, given the labels of two vertices, one can test if they are adjacent in time linear in the size of the labels. Furthermore, given an arbitrary original labeling of the vertices, structure coding labels are found (as above) that are no more than a small constant factor larger than the original labels. These notions are intimately related to vertex-induced universal graphs of polynomial size. For example, planar graphs can be labeled with structure coding labels of size $ < 4\log n$, which i...

Implicit representation of graphs

Living donor renal transplantation has achieved a high level of acceptance from the general public and is the ideal renal replacement therapy for those with end-stage renal disease. Living donor nephrectomy has been proven safe and is associated with minimal complications and a negligible death rate. 1 The recipient benefits of living donor renal transplantation are multiple: superior patient and graft survival, no prolonged waiting time, decreased incidence of delayed allograft function, and a shorter hospital stay. 2 These superior results and the current shortage of cadaver kidneys provide an incentive to increase the frequency of living donor transplantation. However, a significant disincentive is the invasive nature of the donor nephrectomy and its relatively long postoperative recovery period. Recent reports of laparoscopically assisted living donor nephrectomy have shown that this less invasive approach results in reduced postoperative pain, a shorter hospital stay, and a more rapid return to the work for the donor. 3–6 In addition, decreased donor discomfort and a shorter convalescence have resulted in a substantially increased rate of consent to living donation and may help to alleviate the ongoing transplant organ shortage.

A critical analysis with regard to the rate of donor complications and death and the status of the procured kidney is needed before laparoscopic living donor nephrectomy can be fully accepted by the transplant community. In particular, the excellent immediate renal allograft function usually obtained with standard open donor nephrectomy must be reproduced with the laparoscopic technique. A major concern regarding laparoscopic living donor nephrectomy is compelling evidence demonstrating that the prolonged CO2 pneumoperitoneum during laparoscopy decreases renal blood flow and contributes to postoperative renal dysfunction in the recipient. 7,8 The combination of prolonged CO2 pneumoperitoneum and an ischemic period during organ procurement may expose these grafts to an increased risk of early posttransplant renal dysfunction. The purported adverse effects of pneumoperitoneum on renal function have been supported by the initial reports of laparoscopic donor nephrectomy, which suggest either a decrease in urine output during the donor operation or early renal allograft dysfunction. 3,5,6

Gaseous pneumoperitoneum has been found to induce significant systemic hemodynamic alterations that appear to depend on the type of gas, the magnitude of intraabdominal pressure, the baseline hemodynamic function, and intravascular volume status. The cardiovascular effects most frequently associated with CO2 pneumoperitoneum are tachycardia, increased total peripheral resistance, and decreased stroke volume. 8–10 Some investigators have also reported a decrease in cardiac output, but previous studies from our laboratory showed that cardiac output decreased only in hypovolemic animals. 11,12 The effects of intravascular volume expansion on renal blood flow and function during prolonged CO2 pneumoperitoneum remain unknown. Hypertonic saline volume expansion has been shown to improve renal blood flow in other animal models of hypovolemia. 13,14 The use of hypertonic saline solution for volume expansion may provide protection to the kidneys without significant fluid overload to the donor.

The objectives of this study were to test the hypothesis that intravascular volume expansion would improve renal blood flow and function during prolonged CO2 pneumoperitoneum, and to compare the beneficial effects of volume expansion on renal hemodynamics using isotonic (normal saline) and hypertonic (2400 mOsm NaCl) solutions.

Steven M. Rudich

Papers

Effect of waiting time on renal transplant outcome

Proinflammatory Phenotype of Perivascular Adipocytes: Influence of High-Fat Feeding

Experience With More Than 500 Minimally Invasive Hepatic Procedures

Implicit representation of graphs

Effect of Intravascular Volume Expansion on Renal Function During Prolonged CO2 Pneumoperitoneum