Pulsatile machine perfusion with Vasosol solution improves early graft function after cadaveric renal transplantation

BACKGROUND: Cold storage is the most common method of preservation in renal transplantation, but pulsatile machine perfusion (MP) is increasingly used for purposes of ex vivo assessment and resuscitation of high risk allografts. Vasosol (VSL) MP solution (MPS) (Pike Laboratories Inc, Eagle, PA) is a novel perfusate with enhanced vasodilatory and antioxidant capacity. We report our experience with VSL in machine preservation of renal allografts. METHODS: Locally procured cadaver kidney pairs undergoing MP were randomized to VSL or control solution (Belzer MPS; Trans-Med, Elk River, MN). En bloc perfusion was performed according to standard MP procedures. Transplantation was performed at 1 of 12 local transplant centers. Donor and recipient data were collected prospectively. RESULTS: Data from 162 transplanted kidneys were analyzed. A total of 82 renal grafts were perfused with VSL, and 80 were perfused with control solution. No organs were lost secondary to the technique of MP. There was no difference in donor or recipient age between groups. Kidneys perfused with VSL exhibited significantly higher rates of immediate function and significantly less delayed graft function (12.2% vs. 21.2%). Discharge creatinine and length of stay were also significantly improved in the VSL group. One-year graft and patient survivals were equivalent (95%) in both groups. CONCLUSIONS: VSL improved early graft function and shortened the length of stay compared with Belzer MPS. Further improvement in preservation solutions in conjunction with pulsatile perfusion shows promise in improving early outcomes after renal transplantation, especially for extended criteria donor kidneys.     

Homocysteine effect on protein degradation rates

OBJECTIVES: To show the effect of homocysteine (Hcy) on the degradation rates of proteins. DESIGN AND METHODS: Degradation rates of short-lived proteins in neutrophils were measured in in vivo human model of elevated plasma Hcy and lower vitamin status and in animal model of Hcy added in vitro to rat neutrophils. RESULTS: In the human study, we found significant coefficients of correlation between plasma total homocysteine (tHcy) and the degradation rates of 21 protein fractions. In the animal model, Hcy significantly increased degradation rates of 57 protein fractions. CONCLUSIONS: The increase in protein degradation rates, induced by Hcy, may provide a clue to our understanding of the mechanism of Hcy detrimental effects. Hcy may amplify the specific effect of cellular solutes on protein conformation, thereby monitor protein degradation rates to control enzyme activity. Consequently, the cell may lose its ability to maintain an efficient control of some crucial metabolic pathways, possibly leading to atherogenesis.     

Monitoring genotoxicity during the photocatalytic degradation of p-nitrophenol

p-Nitrophenol is a common structural unit of many pesticides and was chosen as a model compound to monitor genotoxicity during photocatalytic degradation. The genotoxicity of p-nitrophenol (PNP) and its breakdown products was measured using a bioluminescent bacterial bioassay, Vitotox. The genotoxic potential decreased with the concomitant photocatalytic degradation of the parent PNP concentration. The rate of genotoxicity reduction was slower than the rate of removal of the parent PNP, due to the formation of genotoxic by-products. After 6 h of photocatalytic treatment the total genotoxicity was removed. These results indicate that bioassays can be used as a simple and highly sensitive method for monitoring the general toxicity of chemical pollutants before, during and after photocatalytic treatment or other destructive processes.     

CD20-mediated apoptosis: signalling through lipid rafts

CD20 is an effective target for therapeutic B-cell depletion with monoclonal antibodies. One proposed mechanism of action is direct cytotoxicity mediated via tyrosine kinase-dependent signalling pathways activated upon CD20 cross-linking. The association of CD20 with membrane microdomains known as lipid rafts, enriched in src-family tyrosine kinases and other signalling effectors, suggests an indirect mechanism of anti-CD20-induced apoptosis in which activation of src-family kinases occurs as a consequence of lipid raft clustering.     

Hyperhomocysteinemia and vitamin score: correlations with silent brain ischemic lesions and brain atrophy

Elevated fasting plasma total homocysteine concentration (tHcy) and lower vitamin status are associated with atherosclerotic states. Silent brain ischemic lesions and brain atrophy, prevailing in the elderly, are affected by tHcy and vitamin status. The study was performed on 56 outpatients who had undergone brain computed tomography (CT) before the onset of the study. According to brain CT evaluation, three groups were set: minor brain ischemia, brain atrophy and control. Brain CT, tHcy, plasma pyridoxal phosphate (PLP), vitamin B(12), folic acid and cognitive and functional capacities were measured or evaluated in all of the subjects. Plasma vitamin score for three vitamins was calculated. In subjects with minor brain ischemic lesions (n = 21), tHcy was higher by 5.6 microM, whereas vitamin score and cognitive function were lower than in controls (n = 24). In subjects with brain atrophy (n = 11), plasma PLP and cognitive function were lower. Particular attention should be paid to tHcy monitoring, vitamin status assessment and brain impairment evaluation.     

A SAGE (serial analysis of gene expression) view of breast tumor progression

To identify molecular alterations involved in the initiation and progression of breast carcinomas, we analyzed the global gene expression profiles of normal mammary epithelial cells and in situ, invasive, and metastatic breast carcinomas using serial analysis of gene expression (SAGE). We identified sets of genes expressed only or most abundantly in a specific stage of breast tumorigenesis or in a certain subtype of tumors through the pair-wise comparison and by hierarchical clustering analysis of these eight SAGE libraries (two/stage). On the basis of these comparisons, we made the following observations: Normal mammary epithelial cells showed the most distinct and least variable gene expression profiles. Many of the genes highly expressed in normal mammary epithelium and lost in carcinomas encoded secreted proteins, cytokines, and chemokines, implicating abnormal paracrine and autocrine signaling in the initiation of breast tumorigenesis. Very few genes were universally up-regulated in all tumors regardless of their stage and histological grade, indicating a high degree of diversity at the molecular level that likely reflects the clinical heterogeneity characteristic of breast carcinomas. Tumors of different histology type and stage had very distinct gene expression patterns. No genes seemed to be specific for metastatic or for in situ carcinomas. We found that the most dramatic and consistent phenotypic change occurred at the normal-to-in situ carcinoma transition. This observation, combined with the fact that many of the genes involved encode secreted, cell-nonautonomous factors, implies that the normal epithelium-to-in situ carcinoma transition may be the most promising target for cancer prevention and treatment.     

Pneumocystis carinii pneumonia studied by gallium-67 scanning

The validity and reliability of gallium-67 (Ga-67) scanning for diagnosis and follow-up of Pneumocystis carinii pneumonia (PCP) were assessed in 34 patients thought to have pulmonary complications of acquired immunodeficiency syndrome (AIDS). Overall sensitivity was 94% and specificity 74%. Among patients with normal or equivocal chest radiographs at the time of admission, sensitivity was 86% and specificity 85%. The authors consider Ga-67 scanning a valid and reliable adjunct in the diagnosis of PCP in AIDS patients with respiratory symptoms when the chest radiograph is normal or equivocal.