Blood-derived macrophages infiltrate the retina and activate Muller glial cells under experimental choroidal neovascularization

Inflammation is a major mechanism in the pathogenesis of age-related macular degeneration, the most important cause of blindness in the elderly. Previous studies have focused on the role of macrophages in regulating the growth of pathological new vessels over the retina, called choroidal neovascularization (CNV). However, no research has been done to evaluate the role of inflammation as a mechanism of vision loss and retinal degeneration in the retina underlying CNV. In other neuropathological conditions, hematogenous macrophages and/or resident microglia contribute to neurodegeneration. We have combined laser-induced CNV in mice and bone marrow transplantation with GFP-labeled bone marrow to determine the relative role of recruited blood-derived macrophages versus resident microglia in the retina associated with CNV. Using these chimeric mice, we have found that many GFP-labeled cells infiltrated the retina underlying CNV but not the retina unaffected by CNV. Immunostaining for the cell adhesion molecules VCAM 1, ICAM 1, and PECAM was strongly upregulated in retinal blood vessels under CNV. All GFP-labeled cells were immunoreactive for the macrophage marker F4/80. Most (70%) of the F4/80 immunoreactive cells were GFP-labeled under CNV. The density of resident microglia did not increase. Most GFP-labeled cells were found in close proximity to activated Muller cells. Depleting circulating macrophages with clodronic acid diminished the density of F4/80 immunoreactive cells as well as the density of pERK immunoreactive Muller cells in the retina under CNV. Thus, recruitment of blood-derived macrophages more than resident microglia seems to be associated with CNV.     

Ultrasound measurements of intraabdominal fat estimate the metabolic syndrome better than do measurements of waist circumference

BACKGROUND: We recently developed an ultrasound technique to estimate intraabdominal fat (IAF). This method is more accurate than measurement of waist and hip circumferences and is simpler and less expensive than computed tomography or magnetic resonance imaging. OBJECTIVE: We compared the associations of ultrasound and waist-circumference (WC) measurements of IAF with other components of the metabolic syndrome. DESIGN: IAF was determined in 600 consecutive participants in the Secondary Manifestations of Arterial Disease (SMART) study. The mean (+/- SD) age was 56.1 +/- 12.6 y, 30.0% of participants were women, and the mean body mass index (BMI; in kg/m2) was 26.6+/- 4.1. RESULTS: IAF increased with age (ultrasound: r = 0.28; WC: r = 0.25; P < 0.001 for both). Higher IAF, as measured by ultrasound but not by WC, was independently associated with higher metabolic risk factors. The correlation coefficients between IAF measured by ultrasound and plasma glucose, total cholesterol, HDL cholesterol, and triacylglycerol were 0.13, 0.16, -0.13, and 0.25, respectively (all P < 0.001; adjusted for age, sex, and BMI). The corresponding coefficients for IAF measured by WC were 0.17 (P < 0.001) and 0.01, -0.06, and 0.05 (all NS). CONCLUSIONS: These results confirm the findings of computed tomography and magnetic resonance imaging investigations. When IAF is measured by ultrasound, the associations are more pronounced than when WC measurements are used and are independent of BMI. This suggests that IAF can be more reliably assessed by ultrasound measurements than by WC measurements.     

Increasing hematocrit reduces early posttransplant cardiovascular risk in diabetic transplant recipients

BACKGROUND: Cardiovascular disease remains epidemic in transplant recipients, despite aggressive treatment of cardiovascular risk factors. Thus, novel risk factors could play a role in the genesis of cardiovascular events in this population. METHODS: We evaluated the impact of early posttransplant anemia on cardiovascular events. We examined rolling average hematocrit values at 30-day intervals and determined the effect of increasing hematocrit on the risk for cardiovascular (CV) events in a single-center population of 404 type 1 diabetic end-stage renal disease patients who underwent either cadaveric kidney transplantation alone or simultaneous pancreas-kidney transplantation. RESULTS: Greater than 60% of the individuals in the study cohort had hematocrit less than or equal to 30% at least once during the first 30 days posttransplant. Forty-two individuals (10.4% of the study population) had at least one 30-day rolling hematocrit less than or equal to 30% and a CV event (myocardial infarction, CV death, angina, congestive heart failure) during the first 26 weeks of the posttransplant course. Increasing hematocrit (>30%) led to a reduction in the risk ratio (RR) for a CV event compared with hematocrit less than or equal to 30% (RR, 0.237; P=0.015). The association between anemia and CV events remained statistically significant in a multivariate analysis (RR, 0.65; P=0.022) that also included age and a history of pretransplant ischemic heart disease. CONCLUSIONS: These data suggest that anemia is an important risk factor for early posttransplant CV events in a high-risk population. Prospective studies of anemia management therapy in this setting are warranted to determine whether this will reduce early posttransplant CV risk.     

Hepatic preconditioning after prolonged warm ischemia by means of S-adenosyl-L-methionine administration in pig liver transplantation from non-heart-beating donors

BACKGROUND: This study ascertained the effect of S-adenosyl-L-methionine (SAMe) administration on the ischemia-reperfusion injury associated with pig liver transplantation from non-heart-beating donors (NHBDs) after prolonged warm ischemia. METHOD: Twenty-five animals underwent transplantation with an allograft from an NHBD. After donor cardiac arrest, cardiopulmonary bypass and normothermic recirculation (NR) were performed for 30 min. Ten animals were given SAMe during NR. Donors were cooled to 15 degrees C, and liver procurement was performed. RESULTS: SAMe reduced histologic liver damage 5 days after transplantation. The necrotic area affected 15.9%+/-14.5% of the liver biopsies in controls and 7.4%+/-9% in SAMe livers. Six of eight controls and only one of eight survivors in the SAMe group developed ischemic cholangitis. SAMe reduced apoptosis of hepatocytes 5 days after transplantation and apoptosis of sinusoidal endothelial cells at reperfusion and at 5 days. SAMe increased energy charge at the end of NR and favored the balance between adenosine and xanthine. It was also associated with higher portal blood flow (740+/-59.2 vs. 475.2+/-65.0 mL/min-1/m-2), hepatic hyaluronic acid extraction (132+/-72.2 vs. -205.8+/-64.6 microg/L), and lower levels of alpha-glutathione-S-transferase after reperfusion (2,601%+/-581% with respect to baseline vs. 6,488%+/-5,612%). CONCLUSION: SAMe administration during liver procurement from NHBDs prevents liver endothelial, parenchymal, and biliary tract damage. The protective role of SAMe may be partially mediated by the effect of adenosine during liver procurement.     

Gastric heterotopia in the nasopharynx causing airway obstruction in the newborn

We describe a newborn boy with a gastric heterotopia located in the nasopharynx, which caused airway obstruction soon after delivery. Gastric heterotopia is an uncommon lesion generally found throughout the alimentary tract, but nasopharynx is an exceptional location. To our knowledge, this is the second reported case of gastric heterotopia located in the nasopharynx, and the first one presenting in a newborn with symptoms at birth and with an associated central nervous system mass.     

Helicobacter pylori: focus on CagA and VacA major virulence factors

After colonizing the human gastric mucosa, Helicobacter pylori can remain within the host for years and even decades, and is associated with several, highly significant gastric pathologies. In Mexico, the seroprevalence at 1 year of age is 20% and the estimated increment in seropositivity per year is 5% for children aged 1-10 years. More than 80% of adults are infected by the time they are 18-20 years old. Bacterial virulence factors have been proposed for H. pylori, such as urease, flagella, heat-shock protein, lipopolysaccharide, adhesions, vacuolating cytotoxin, cag pathogenicity island and the cytotoxin-associated protein, the latter being the most studied mechanism to date.     

Combined therapy in the treatment of dens invaginatus: case report

Dens invaginatus is an anomaly that has numerous complex forms. Whenever endodontic therapy involving such a tooth becomes necessary, the clinician must be aware of the various treatments available for proper care. We present a case report of a maxillary lateral incisor having the anomaly in which both nonsurgical and surgical treatment was performed.     

The scientific rationale and development of an optimized dentifrice for the treatment of dentin hypersensitivity

PURPOSE: To describe the development of a new dentin hypersensitivity treatment, Colgate Sensitive Maximum Strength dentifrice, containing 5% potassium nitrate as the anti-hypersensitivity active agent. The objective was to develop a home-use hypersensitivity dentifrice that would be superior to the market leader, improving on what is available, which also contains 5% potassium nitrate as the anti-hypersensitivity active agent. METHODS: In vivo (clinicals, taste evaluation and rat caries), in vitro (potassium flux) and analytical (rheology, dispensed volume, scanning electron microscopy, electron scanning chemical analysis and radioactive dentin abrasion) methods were performed. RESULTS: The objective was accomplished with the development of a new activated silica technology that resulted in enhanced potassium ion activity. In vitro documentation, supported by clinical studies, demonstrated that the resulting formula is more effective than the market leader for relief of hypersensitivity pain. Fast pain relief in less than 2 weeks and long-lasting protection against pain with regular use have also been clinically documented. Furthermore, FDA-required in vivo and in vitro studies indicate that this formula, which contains 0.45% stannous fluoride (1100 ppm fluoride) as the anti-caries active agent, is effective against caries. Good taste, acceptable rheology, acceptable abrasivity, and cosmetic and chemical stability have all been engineered into this unique dentin hypersensitivity treatment. In summary, a highly efficacious consumer friendly treatment for dentin hypersensitivity has been developed.