Cross-sectional studies show that white adipose tissue hypertrophy (few, large adipocytes), in contrast to hyperplasia (many, small adipocytes), associates with insulin resistance and increased risk of developing type 2 diabetes. We investigated if baseline adipose cellularity could predict improvements in insulin sensitivity following weight loss.
Plasma samples and subcutaneous abdominal adipose biopsies were examined in 100 overweight or obese individuals before and 10 weeks after a hypocaloric diet (7±3% weight loss) and in 61 obese subjects before and 2 years after gastric by-pass surgery (33±9% weight loss). The degree of adipose tissue hypertrophy or hyperplasia (termed the morphology value) in each individual was calculated on the basis of the relationship between fat cell volume and total fat mass. Insulin sensitivity was determined by homeostasis model assessment-estimated insulin resistance (HOMAIR).
In both cohorts at baseline, subjects with hypertrophy displayed significantly higher fasting plasma insulin and HOMAIR values than subjects with hyperplasia (P
The mucosa of the small intestine encompasses about 90% of the luminal surface area of the digestive system, but only 2% of the total annual gastrointestinal cancer incidence in the United States.
The remarkable contrast in age-standardized cancer incidence between the small and large intestine has been reviewed with respect to the cell type patterns, demographic features, and molecular characteristics of neoplasms.
Particularly noteworthy is the predominance of adenocarcinoma in the colon, which exceeds 98% of the total incidence by cell type, in contrast to that of 30% to 40% in the small intestine, resulting in an age-standardized ratio of rates exceeding 50-fold. The prevalence of adenomas and carcinomas is most prominent in the duodenum and proximal jejunum. The positive correlation in global incidence rates of small and large intestinal neoplasms and the reciprocal increases in risk of second primary adenocarcinomas suggest that there are common environmental risk factors. The pathophysiology of Crohn inflammatory bowel disease and the elevated risk of adenocarcinoma demonstrate the significance of the impaired integrity of the mucosal barrier and of aberrant immune responses to luminal indigenous and potentially pathogenic microorganisms.
In advancing a putative mechanism for the contrasting mucosal susceptibilities of the small and large intestine, substantial differences are underscored in the diverse taxonomy, concentration and metabolic activity of anaerobic organisms, rate of intestinal transit, changing pH, and the enterohepatic recycling and metabolism of bile acids. Experimental and epidemiologic studies are cited that suggest that the changing microecology, particularly in the colon, is associated with enhanced metabolic activation of ingested and endogenously formed procarcinogenic substrates.
Cites: Gastroenterol Clin North Am. 2007 Dec;36(4):927-46, viii17996798
Cites: Annu Rev Pathol. 2007;2:401-2918039105
Cites: Cancer Epidemiol Biomarkers Prev. 2007 Dec;16(12):2533-4718086756
Neutrophil influx into tissues occurs in many diverse diseases and can be associated with both beneficial and injurious effects. We hypothesize that the stimulus for certain neutrophilic inflammatory responses can be reduced to a series of competing reactions for iron, with either a labile or reactive coordination site available, between host chelators and chelators not indigenous to that specific living system. The iron focuses the transport of host phagocytic cells through a metal catalyzed generation of oxidant sensitive mediators including cytokines and eicosanoids. Many of these products are chemotactic for neutrophils. We also postulate that the iron increases the activity of the phagocyte associated NADPH oxidoreductase in the neutrophil. The function of this enzyme is likely to be the generation of superoxide in the host's attempt to chemically reduce and dislodge the iron from its chelate complex. After the reoxidation of Fe2+ in an aerobic environment, Fe3+ will be coordinated by host lactoferrin released by the neutrophil. When complexed by this glycoprotein, the metal does not readily undergo oxidation/reduction and is safely transported to the macrophages of the reticuloendothelial system where it is stored in ferritin. Finally, we propose that the neutrophil will attempt to destroy the chelator not indigenous to the host by releasing granular contents other than lactoferrin. Inability to eliminate the chelator allows this sequence to repeat itself, which can lead to tissue injury. Such persistence of a metal chelate in the host may be associated with biomineralization, fibrosis, and cancer.
PURPOSE: To study the effect of two incision sizes, 5.2 and 11.0 mm, on the inflammatory response in rabbit eyes after lens extraction with phacoemulsification. SETTING: S:t Erik's Eye Hospital, Stockholm, and Pharmacia, Uppsala, Sweden. METHODS: Bilateral endocapsular phacoemulsification was performed on 32 rabbits. The wound was enlarged to 5.2 mm, and a poly(methyl methacrylate) intraocular lens (IOL) was implanted in the capsular bag. In each rabbit, one eye was selected at random and the wound in that eye enlarged to 11.0 mm. In both eyes the wound was sutured with a 9-0 polypropylene continuous suture. The number of white blood cells (WBCs) and prostaglandin E2 (PGE2) in the aqueous humor were measured at days 1, 3, 7, and 28 postoperatively. Corneal thickness was also measured by pachymetry. RESULTS: The number of WBCs at day 3 and the PGE2 levels at days 1, 3, and 7 were significantly higher in eyes with 11.0 mm incisions than in eyes with 5.2 mm incisions. One week after surgery, the corneas in the eyes with 11.0 mm incisions were significantly thicker than in those with 5.2 mm incisions. CONCLUSION: The results indicate that incision size is an important factor in the inflammatory response following phacoemulsification and IOL implantation in the rabbit eye.