Acute inflammation in gram-negative infection: endotoxin, interleukin 1, tumor necrosis factor, and neutrophils

Experimental bacterial infection of the dermis induced with gram-negative microorganisms is associated with an acute inflammatory reaction, which represents the principal local defense against spread of the infection. When the inflammatory reaction is quantitated with radiolabeled cells and proteins, the kinetics resemble acute inflammation induced with other agents, such as immune complexes or chemotaxins. There is an interrelationship between the components or events of the inflammatory reaction; inasmuch as vascular injury is neutrophil-dependent, neutrophils must migrate to the site where the bacteria multiply. In neutropenic animals there is no such emigration and bacterial multiplication is not inhibited. The microorganisms shed endotoxin, which in turn induces secretion of interleukin 1 (IL 1) and probably tumor necrosis factor. Endotoxin is the most potent agent (10(-15) mol vs. 10(-12) mol of C5ades Arg) capable of inducing a neutrophil influx. Desensitization or tachyphylaxis of the tissues (probably of postcapillary venular endothelium) to IL 1 seems to control cessation of the neutrophil influx (also in vitro evidence). Phagocytosis of the bacteria by neutrophils is associated with release of oxygen radicals and lysosomal proteases from the neutrophils. These are instrumental in eliciting microvascular injury, which is characterized by enhanced vasopermeability, hemorrhage, and thrombosis.     

Use of activated clotting time for monitoring anticoagulation during cardiopulmonary bypass in infants and children with congenital heart disease

The use of a fixed dosage schedule was compared with the use of activated clotting time (ACT) for determining heparin and protamine dosages during and after cardiopulmonary bypass disease. Use of the ACT resulted in a statistically significant increase in heparin dosage and a statistically significant reduction of postoperative blood loss. With ACT use, chest tubes were retained for a shorter period of time, and the incidence of serious postoperative hemorrhage was reduced from 44% to 18%. These results confirm the superiority of the ACT method for monitoring intraoperative anticoagulation in pediatric patients with congenital heart disease.     

Plant virus infection development as affected by heavy metal stress

The work was focused on the investigation of possible dependencies between the development of viral infection in plants and the presence of high heavy metal concentrations in soil. Field experiments have been conducted in order to study the development of systemic tobacco mosaic virus (TMV) infection in Lycopersicon esculentum L. cv. Miliana plants under effect of separate salts of heavy metals Cu, Zn and Pb deposited in soil. As it is shown, simultaneous effect of viral infection and heavy metals in tenfold maximum permissible concentration leads to decrease of total chlorophyll content in experiment plants mainly due to the degradation of chlorophyll a. The reduction of chlorophyll concentration under the combined influence of both stress factors was more serious comparing to the separate effect of every single factor. Plants' treatment with toxic concentrations of lead and zinc leaded to slight delay in the development of systemic TMV infection together with more than twofold increase of virus content in plants that may be an evidence of synergism between these heavy metal's and virus' effects. Contrary, copper although decreased total chlorophyll content but showed protective properties and significantly reduced amount of virus in plants.     

Proteomic approach: Identification of <Emphasis Type="Italic">Medicago truncatula</Emphasis> proteins induced in roots after infection with the pathogenic oomycete <Emphasis Type="Italic">Aphanomyces euteiches</Emphasis>

The legume root rot disease caused by the oomycete pathogen Aphanomyces euteiches is one major yield reducing factor in legume crop production. A comparative proteomic approach was carried out in order to identify proteins of the model legume Medicago truncatula which are regulated after an infection with A. euteiches. Several proteins were identified by two dimensional gel electrophoresis to be differentially expressed after pathogen challenge. Densitometric evaluation of expression values showed different regulation during the time-course analysed. Proteins regulated during the infection were identified by matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS). Among the differentially expressed proteins, two encoded putative cell wall proteins and two were designated as small heat shock proteins. Furthermore, an isoform of the chalcone-O-methyltransferase was found to be increased in infected roots. The majority of induced proteins belonged to the family of class 10 of pathogenesis related proteins (PR10). Previously, various PR10-like proteins have been shown to be regulated by general stress or abscisic acid (ABA). Therefore, these proteins were further investigated concerning their regulation in response to drought stress and exogenous ABA-application. Complex regulation patterns were identified: three of the A. euteiches-induced PR10-like proteins were also induced by exogenous ABA- but none of them is induced after drought stress. In contrast, three of these proteins are down-regulated by drought stress. Hence, the strong expression of different PR10-family members and their regulation profiles indicates that this set of proteins plays a major role during root adaptations to various stress conditions.     

Effects of dietary protein types on immune responses and levels of infection with Eimeria vermiformis in mice

The present study reports the dietary effects of bovine alpha whey fraction, bovine casein and soy protein isolate on the immune responsiveness of C57BL/6J mice infected with Eimeria vermiformis. During the patent period, mice fed alpha whey fraction had significantly higher blood total white cell, CD4+ and CD8+ lymphocyte counts and higher Con A-stimulated IFN-gamma production by spleen cells than those fed other protein sources, but there was no significant difference in output of faecal oocysts. Casein-fed mice had significantly higher levels of Con A- stimulated IFN-gamma production and a lower output of faecal oocysts than soy-fed mice. The study demonstrated that dietary proteins have different impacts on immune responsiveness and level of parasitic infection in the gut; however, the mechanisms affecting level of infection are not clear. These effects appeared not to be solely related to nutritional properties of the diets. Further research into the underlying immune mechanisms and possible direct interactions between bioactive proteins and the parasite E. vermiformis should be fruitful.     

Body Anthropometry and the Risk of Hip and Wrist Fractures in Men: Results from a Prospective Study

Available epidemiological information on the associations between body anthropometry and the incidence of fractures in men is limited. We therefore prospectively investigated the association between body anthropometry and the incidence of hip and wrist fractures from low and moderate trauma among 43,053 men who were 40 years to 75 years of age in 1986 when they first enrolled in the Health Professionals Follow-Up Study. After 8 years of follow-up, 201 wrist fracture cases and 56 hip fracture cases were reported. Greater height was associated with significant elevations in both hip and wrist fractures, whereas nonsignificant inverse associations were observed with weight and body mass index. Men in the highest quintile of waist circumference had a relative risk (RR) of 2.57 (95% confidence interval [CI] 0.64 to 10.3) for hip fracture and 2.05 (95% CI 1.06 to 3.96) for wrist fracture when compared with men in the lowest quintile. Waist-to-hip ratio was also positively related to fracture incidence; comparing highest with lowest quintile, the RRs were 3.92 (95% CI 1.07 to 14.3) for hip fracture and 1.50 (95% CI 0.85 to 2.66) for wrist fracture. These anthropometric indicators, in particular waist-to-hip ratio, may be useful for the prediction of hip fracture in adult men.     

Cytoskeletal anchoring of GLAST determines susceptibility to brain damage: an identified role for GFAP

Glial fibrillary acidic protein (GFAP) is an enigmatic protein; it currently has no unambiguously defined role. It is expressed in the cytoskeleton of astrocytes in the mammalian brain. We have used co-immunoprecipitation to identify in vivo binding partners for GFAP in the rat and pig brain. We demonstrate interactions between GFAP, the glutamate transporter GLAST, the PDZ-binding protein NHERF1, and ezrin. These interactions are physiologically relevant; we demonstrate in vitro that transport of D-aspartate (a glutamate analogue) is significantly increased in the presence of GFAP and NHERF1. Moreover, we demonstrate in vivo that expression of GFAP is essential in retaining GLAST in the plasma membranes of astrocytes after an hypoxic insult. These data indicate that the cytoskeleton of the astrocyte plays an important role in protecting the brain against glutamate-mediated excitotoxicity.     

Alcohol Intake and 8‐Year Weight Gain in Women: A Prospective Study

Objective: To examine prospectively the relationship between alcohol and 8‐year weight gain in women. Research Methods and Procedures: A prospective study of 49, 324 women 27 to 44 years old who did not have a history of cardiovascular disease, cancer, or diabetes, who were not pregnant during the study period, and who reported weights in 1991 and 1999. Results: In cross‐sectional analyses, there was a significant inverse relationship between alcohol and BMI even after adjustment for dietary factors and a wide range of confounders. In multivariate prospective analyses, a nonlinear relationship was seen between alcohol and weight gain (≥5 kg) in all women. Compared with nondrinkers, the adjusted relative odds [95% confidence interval (CI)] of weight gain according to grams per day were 0.94 (0.89, 0.99) for those consuming 0.1 to 4.9 g/d, 0.92 (0.85, 0.99) for 5 to 14.9 g/d, 0.86 (0.76, 0.78) for 15 to 29.9 g/d, and 1.07 (0.89, 1.28) for those consuming 30+ g/d (p < 0.0001 for quadratic trend). Women who continued to drink heavily and those who became heavy drinkers showed similar increased odds of weight gain. The increased odds of weight gain associated with heavy drinking (30+ g/d) were most marked in the younger women (<35 years) (odds ratio 1.64; 5% CI 1.03 to 2.61). In African‐American women, light drinking was associated with increased odds of weight gain compared with nondrinkers (odds ratio = 2.43; 95% CI 1.22 to 4.82) Discussion: Our data suggest that light to moderate drinking (up to 30 g/d) is not associated with weight gain in women except possibly in African‐American women. Heavier drinking may promote weight gain in women.     

Life Years Lost Associated with Obesity-Related Diseases for U.S. Non-Smoking Adults

The objectives of this paper are to predict life years lost associated with obesity-related diseases (ORDs) for U.S. non-smoking adults, and to examine the relationship between those ORDs and mortality. Data from the National Health Interview Survey, 1997–2000, were used. We employed mixed proportional hazard models to estimate the association between those ORDs and mortality and used simulations to project life years lost associated with the ORDs. We found that obesity-attributable comorbidities are associated with large decreases in life years and increases in mortality rates. The life years lost associated with ORDs is more marked for younger adults than older adults, for blacks than whites, for males than females, and for the more obese than the less obese. Using U.S. non-smoking adults aged 40 to 49 years as an example to illustrate percentage of the life years lost associated with ORDs, we found that the mean life years lost associated with ORDs for U.S. non-smoking black males aged 40 to 49 years with a body mass index above 40 kg/m² was 5.43 years, which translates to a 7.5% reduction in total life years. White males of the same age range and same degree of obesity lost 5.23 life years on average – a 6.8% reduction in total life years, followed by black females (5.04 years, a 6.5% reduction in life years), and white females (4.7 years, a 5.8% reduction in life years). Overall, ORDs increased chances of dying and lessened life years by 0.2 to 11.7 years depending on gender, race, BMI classification, and age.