Oxidative tissue damage following regional intestinal ischemia and reperfusion in the cat

Regional intestinal ischemia in cats resulted in an accumulation of hypoxanthine within 2 h, the concentration of which rose from 0.062 to 1.131 nmol/mg protein. A similar rise in AMP content (from 0.5 to 3.2 nmol/mg protein) was observed, but not in the ADP level. In parallel, ATP content decreased from 7.5 to 2.8 nmol/mg protein. Reperfusion of the ischemic tissue was followed by rapid metabolism of the purine metabolites; after 1 h of reperfusion the tissue level of hypoxanthine was 0.186 nmol/mg protein, of AMP 0.7 nmol/mg protein, and of ATP 4.3 nmol/mg protein. The oxidation of hypoxanthine, mediated by xanthine oxidase, is accompanied by the release of superoxide ions. Consequently, the concentration of oxidized glutathione was doubled upon reperfusion, while marked lipid peroxidation took place, as evidenced by the rise in conjugated diene content from 2.8 mumol/g tissue before reperfusion to 5.6 mumol/g tissue after 10 min of reoxygenation. In line with these findings is the fact that histologically observable damage occurred mainly in the presence of oxygen. These data indicate that, at least in our model, rapid reoxygenation is a major cause of "ischemic" tissue damage.     

Women's angiographic vitamin and estrogen trial: design and methods

The Women's Angiographic Vitamin and Estrogen trial was a randomized, double-blind, placebo-controlled study designed to test the efficacy of estrogen replacement and antioxidant vitamins for preventing angiographic progression of coronary artery disease. Postmenopausal women with one or more angiographically documented coronary stenoses of 15-75% at baseline were assigned in a 2 x 2 factorial randomization to active hormone replacement therapy (conjugated estrogens for women who had had a hysterectomy or conjugated estrogens with medroxyprogesterone for women with intact uteri) or placebo and to active vitamins E and C or their placebos. Seven clinical centers, five in the United States and two in Canada, randomized 423 women between July 1997 and July 1999. Quantitative coronary angiography was performed at baseline and repeated after projected mean follow-up of 3 years.     

Vaccination with outer membrane complexes elicits rapid protective immunity to multidrug-resistant Acinetobacter baumannii

Acinetobacter baumannii causes pneumonias, bacteremias, and skin and soft tissue infections, primarily in the hospitalized setting. The incidence of infections caused by A. baumannii has increased dramatically over the last 30 years, while at the same time the treatment of these infections has been complicated by the emergence of antibiotic-resistant strains. Despite these trends, no vaccines or antibody-based therapies have been developed for the prevention of A. baumannii infection. In this study, an outer membrane complex vaccine consisting of multiple surface antigens from the bacterial membrane of A. baumannii was developed and tested in a murine sepsis model. Immunization elicited humoral and cellular responses that were able to reduce postinfection bacterial loads, reduce postinfection proinflammatory cytokine levels in serum, and protect mice from infection with human clinical isolates of A. baumannii. A single administration of the vaccine was able to elicit protective immunity in as few as 6 days postimmunization. In addition, vaccine antiserum was used successfully to therapeutically rescue naïve mice with established infection. These results indicate that prophylactic vaccination and antibody-based therapies based on an outer membrane complex vaccine may be viable approaches to preventing the morbidity and mortality caused by this pathogen.Acinetobacter baumannii causes different types of infections, including, among others, pneumonia, bacteremia, meningitis, and skin and soft tissue infections (24).Over the last 3 decades, A. baumannii has emerged as a pathogen of increasing clinical importance due to the global increase in the incidence of infections caused by this organism. A. baumannii was shown to be the causative agent in 6.9% of nosocomial pneumonias in 2003 in a national surveillance study performed in the United States, which represents a 72% increase compared to data collected in 1986 (14). In addition, A. baumannii was the causative agent in 2.4% of bacteremias and 6.2% of bacteremias in intensive care units (14, 39). Infections caused by this pathogen have been especially problematic in patients receiving mechanical ventilation, in burn patients, and in military personnel sustaining war-related trauma in Iraq and Afghanistan. A. baumannii can cause outbreaks in intensive care units and trauma/burn units, which are presumably caused by passage of the organism from infected or colonized individuals and contaminated hospital equipment to uninfected patients. Although A. baumannii causes primarily nosocomial infections, recent reports have described community-acquired pneumonias caused by this pathogen (16, 25). Mortality rates associated with A. baumannii infection have been reported to be between 35 and 70% for nosocomial pneumonias (37) and between 20 and 60% for bacteremic infections (14, 39).The treatment of infections caused by A. baumannii has become difficult due to the emergence of multidrug-resistant strains. A. baumannii has demonstrated the ability to acquire resistance to diverse classes of antibiotics via multiple resistance mechanisms (40). Carbapenems have been the standard treatment for A. baumannii infections; however, increasing resistance rates have limited their efficacy. Surveillance studies performed in 2007 showed that resistance rates to imipenem were between 38 and 71%, whereas 20 years ago resistance to imipenem was exceedingly rare (37). Due to increasing resistance to commonly used antibiotics, clinicians have relied increasingly upon the use of the polymyxin antibiotic colistin (15). However, the emergence of strains resistant to colistin has now been reported (1, 5). Of particular concern are recent reports describing outbreaks of panresistant strains, which are resistant to all standard antimicrobials (33, 34). Given these trends, the development of new strategies for preventing and treating infections caused by this pathogen is necessary.Immunization represents a potentially effective strategy for preventing infections caused by A. baumannii; however, to date, there have been no vaccines developed for this pathogen. Vaccines that elicit antibodies against bacterial outer membrane proteins are attractive candidates due to the role of these proteins in interacting with the host and their availability for antibody neutralization due to their localization on the cell surface.Vaccines based on inactivated whole cells and attenuated strains are able to elicit antibodies against multiple surface proteins; however, the administration of whole organisms raises potential safety concerns. One approach that has been used to elicit antibodies against multiple bacterial surface proteins without the administration of whole organisms is the development of vaccines based on proteins extracted from the bacterial outer membrane, termed outer membrane complex (OMC) vaccines (4, 10, 17). OMC vaccines have been shown to elicit antibodies against multiple proteins of the bacterial outer membrane and to induce protective immunity against infection and have given promising results in early human clinical trials (4, 10, 17-19). The objective of the present study was to develop an OMC vaccine against A. baumannii and to characterize its efficacy in a murine sepsis model. In addition, the ability of antisera from vaccinated mice to passively protect and treat naïve mice was tested.     

Asymmetric Dimethylarginine (ADMA) and Progression of Nephropathy in Patients with Type 2 Diabetes

Diabetic nephropathy is the leading cause of kidney failure all over the world. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide (NO) synthase. ADMA is in part eliminated via urinary excretion. It is found to be elevated in end stage renal disease. Identification of the plasma concentrations of ADMA in patients with different stages of diabetic nephropathy compared with healthy age-matched control subjects for estimation of the role of ADMA as a marker of progression of kidney disease in diabetic patients. Seventy-five diabetic patients were divided into five groups: Group I: patients with normoalbuminuria (urinary albumin excretion UAE < 30 mg/d), Group II: patients with microalbuminuria (UAE: 30–300 mg/d), Group III: patients with macroalbuminuria (UAE > 300 mg/d), Group IV: patients one month after renal transplantation and Group V: patients on haemodialysis. Patients were compared to 15 healthy control subjects matched for age and sex. All subjects subjected to thorough clinical examination and laboratory investigations including: serum albumin, urea, creatinine, fasting and postprandial blood glucose, UAE, urinary albumin/creatinine ratio and serum ADMA level. All patients groups had significantly higher levels of ADMA when compared to control group P < 0.01. The levels of ADMA were positively correlated with disease progression and degree of proteinuria. ADMA can be used as a marker of progression of kidney disease among diabetic patients.     

The radial forearm free flap: a review of microsurgical options

The radial forearm free flap, highly regarded in head and neck reconstructive surgery, is known to be one of the most reliable and versatile flaps. The microsurgery is usually easy to perform due to large vessels and a long pedicle; the double superficial and deep venous networks allow many microsurgical options. The sensory nerve coaptation, still debated for weight-bearing foot reconstruction and its sensory restoration, has recently undergone technical refinements. The authors review the microsurgical options for microvascular anastomosis and for sensory restoration.