Application of proteomics technology to the field of neurotrauma

Near-completion of the Human Genome Project has stimulated scientists to begin looking for the next step in unraveling normal and abnormal functions within biological systems. Consequently, there is new focus on the role of proteins in these processes. Proteomics is a burgeoning field that may provide a valuable approach to evaluate the post-traumatic central nervous system (CNS). Although we cannot provide a comprehensive assessment of all methods for protein analysis, this report summarizes some of the newer proteomic technologies that have propelled this field into the limelight and that are available to most researchers in neurotrauma. Three technical approaches (two-dimensional gel electrophoresis, direct analysis by mass spectrometry, including two-dimensional chromatography coupled to mass spectrometry and isotope coded affinity tags, and antibody technologies) are reviewed, and their advantages and disadvantages presented. A discussion of proteomic technology in the context of brain and spinal cord trauma follows, addressing current and future challenges. Proteomics will likely be very useful for developing diagnostic predictors after CNS injury and for mapping changes in proteins after injury in order to identify new therapeutic targets. Neurotrauma results in complex alterations to the biological systems within the nervous system, and these changes evolve over time. Exploration of the "new nervous system" that follows injury will require methods that can both fully assess and simplify this complexity.     

Power rolloff during interactive radiofrequency ablation can enhance necrosis when treating hepatocellular carcinoma

OBJECTIVE: The purpose of this study was to compare the efficacy between standard and interactive radiofrequency ablation for treatment of hepatocellular carcinoma. SUBJECTS AND METHODS: Of 97 patients with 112 nodular hepatocellular carcinomas, 59 hepatocellular carcinomas were ablated using a standard algorithm and 53 hepatocellular carcinomas, using an interactive algorithm. For the procedure using the interactive algorithm, the electrode's array was partially retracted or fully deployed depending on the change of impedance. Complete tumor necrosis was defined as the lack of enhancement on single-detector helical CT at least 4 months after the last radiofrequency ablation. RESULTS: Complete necrosis was achieved in 101 (90%) of 112 hepatocellular carcinomas, with complete necrosis being achieved more frequently in hepatocellular carcinomas undergoing interactive ablation (96%) than standard ablation (85%) (p = 0.034). Power rolloff (a clinical end point in which power decreases as impedance increases) occurred in all of the 53 hepatocellular carcinomas that underwent interactive ablation, whereas power rolloff occurred in 48 (81%) of the 59 hepatocellular carcinomas that underwent standard ablation (p = 0.00053). Complete necrosis occurred more frequently when rolloff was achieved (96%) than without rolloff (36%) (p < 0.0001). Multivariate analysis determined that power rolloff was an independent factor in achieving complete necrosis of hepatocellular carcinomas (p < 0.0001). CONCLUSION: The use of interactive radiofrequency ablation increased the frequency of power rolloff and the rate of complete necrosis in the treatment of hepatocellular carcinoma. Power rolloff was a significant determinant of whether complete necrosis was achieved in hepatocellular carcinomas treated with radiofrequency ablation.     

Chemical burn caused by povidone-iodine alcohol solution--a case report

Burns associated with chemical disinfectants for skin preparation are rare. Skin irritation and maceration associated with pressure factors may contribute to its occurrence. We report a 24-year-old female with thyroid tumor who was admitted for subtotal thyroidectomy. After anesthetic induction, the patient was placed in the supine position with the trunk elevated to 20 degree. The skin over the anterior neck was sterilized with 10% Povidone-iodine (PI) alcohol solution. After a 3-hour surgery, the patient complained of burning pain over the back at the recovery room. Physical examination revealed a 9 x 11 cm area of skin lesion partially thickened amid on the middle of the back suggestive of chemical burn. After conservative treatment, she was discharged uneventfully 4 days later. Upon follow-up, the wound was seen to heal with minimal scarring within 3 weeks.     

Reduced Phagocytosis of Colloidal Carriers Using Soluble CD47

Purpose. This study was designed to illustrate the feasibility of using soluble CD47 protein to antagonize phagocytosis of colloidal drug carriers by macrophages. Methods. Expression of CD47-streptavidin (CD47-SA) fusion protein was achieved in B21CodonPlus host cells following IPTG induction. Murine macrophage cell line J774A.1, expressing high levels of SIRP, was selected as the biologic model system for phagocytosis. FITC-labeled perfluorocarbon (PFC) emulsions were used as the colloidal carriers to trigger phagocytosis. Microscopy (inverted light and UV-fluorescence) and flow cytometry were used to qualitatively and quantitatively determine the degree of phagocytosis, respectively. Results. The bacterially expressed, purified CD47-SA had neither cytotoxic nor cytostatic effects when incubated with J774A.1 cells up to a concentration of 400 nM for 24 h. Phagocytosis of FITC-labeled PFC emulsions was significantly diminished when macrophages were pretreated with 100 nM CD47-SA for 1 h. Conclusions. We demonstrated that soluble CD47-SA antagonized phagocytosis of colloidal carriers to a significant degree by interaction with macrophage SIRP.     

Genetic relationships among populations of Aedes aegypti in Taiwan by using phenotypic and random amplified DNA-polymerase chain reaction markers

An analysis of gene flow was conducted among collections of Aedes aegypti from 7 localities along the southwestern and southeastern coasts in Taiwan. Markers include 7 types of scaling patterns and 23 random amplified polymorphic DNA (RAPD) loci amplified by the polymerase chain reaction. Differences in scaling pattern and in the frequencies of RAPD markers were detected among populations and cluster analyses revealed 2 main groups on each side of the Central Mountain Range. Regression analysis of geographic distances and pairwise F(ST) values estimated from RAPD markers showed that southwestern populations are isolated by distance and that populations within 15 km are panmictic. This is a shorter distance than detected among collections of Ae. aegypti in similar published studies from Mexico and Argentina.     

Acute posterior multifocal placoid pigment epitheliopathy associated with a systemic necrotizing vasculitis

PURPOSE: The authors present a case of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) associated with a systemic necrotizing vasculitis with mixed features of Wegener granulomatosis and polyarteritis nodosa (PAN). METHODS: Case report. RESULTS: A 29-year-old woman developed a severe nosebleed, followed by a low-grade fever, night sweats, and a productive cough. One month later, she began experiencing high fevers, headache, myalgia, neck stiffness, and abdominal pain as well as bilateral blurred vision from APMPPE. Systemic evaluation revealed nasal ulcerations, bilateral pleural effusions, and a bilateral maxillary and ethmoid sinusitis, consistent with Wegener granulomatosis. However, ANCA testing was negative, and a renal and mesenteric angiogram showed aneurysmal dilatations suggestive of PAN. Her ocular and systemic symptoms markedly improved with systemic corticosteroids. CONCLUSIONS: The cause of APMPPE is unknown. This case of APMPPE associated with systemic necrotizing vasculitis provides support for the choroid as being primarily involved by a diffuse vasculitic process that interrupts choroidal perfusion and causes the characteristic fundus findings in APMPPE.     

Pseudomonas corneal ulcer related to overnight orthokeratology

PURPOSE: To report two cases of Pseudomonas aeruginosa corneal ulcers as a complication of overnight orthokeratology lens wear. METHODS: Case report. RESULTS: Two 11-year-old girls with acute central corneal ulcers were referred to our hospital. In both cases, the ulcers were about 2 mm in diameter, located centrally, contained dense cellular infiltration, and discharged purulent material. Intensive topical ceftazidime was applied to treat the ulcers. Cultures of the scraped corneal tissues and the contact lens storage solutions in both cases grew P. aeruginosa, which was sensitive to the antibiotic. The presenting best-corrected visual acuity was hand motion at 20 cm in one patient and 6/20 in the other. Both patients had received several months of overnight orthokeratology treatment with rigid gas permeable contact lenses to correct myopia (-4.25 D and -4.75 D in the two affected eyes). The final best-corrected visual acuity was 6/60 in one patient and 6/7.5 in the other. CONCLUSIONS: Overnight orthokeratology contact lens wear carries a potential risk of corneal ulcer and may cause significant visual impairment in children.     

Possible involvement of nitric oxide in the progression of diabetic retinopathy

Abnormal nitric oxide (NO) synthesis has been implicated in the pathogenesis of diabetes mellitus. The aim of our study was to elucidate the relationship between the stages of diabetic retinopathy (DR) and the NO levels in aqueous humor and plasma. Using the chemiluminescence assay, we measured the concentrations of NO in aqueous humor and plasma samples obtained during intraocular surgery from 45 diabetic patients and 19 nondiabetic cataract patients. The patients with diabetes were classified into 4 groups: proliferative DR (PDR) with active neovascularization (active PDR; 9 cases), PDR with quiescent neovascularization (regressed PDR; 6 cases), background DR (BDR; 16 cases) and no DR (14 cases). We found that the aqueous NO levels (mean +/- SE) of the active PDR group (83.2 +/- 13.9 microM) were significantly higher than those of the BDR group (45.8 +/- 6.0 microM, p = 0.049) and the diabetics without DR (33.3 +/- 5.2 microM, p = 0.011), and, although not statistically significantly, they were also higher than those of the regressed PDR group (52.1 +/- 10.3 microM, p = 0.224). However, no significant differences were observed between any of the diabetic subgroups in the plasma NO levels (p = 0.345). We therefore concluded that NO present in the ocular tissues may play important roles in the progression of DR.     

Association of tumour necrosis factor alpha -308 gene polymorphism with primary open-angle glaucoma in Chinese

PURPOSE: Genetic factors are known to play a role in the aetiology of glaucoma, and in particular the role of the immune system is highly suspected. In this study, we evaluated the association between tumour necrosis factor alpha -308 (TNF alpha -308) and primary open-angle glaucoma (POAG). METHODS: A total of sixty POAG patients and 103 healthy volunteers as control group were enrolled in this case-controlled study. Furthermore, we used polymerase chain reaction based analysis to resolve the TNF alpha -308 polymorphism. Statistical analysis for the relative risk of TNF alpha -308 polymorphism was compared by the chi(2) test. RESULTS: There were significant differences in the distribution of the polymorphism between the POAG patients and the control subjects (P = 0.00016; P < 0.05) and it was found that the A(-308) allele occurred more frequently in POAG patients (odds ratio: 2.72; 95% confidence interval: 1.66-4.45). CONCLUSION: The results of our study concluded that the distribution of TNF alpha -308 was significantly higher in the POAG patients than in the control group. Therefore, the A(-308) allele appears to be associated with POAG and, therefore, could be used as a genetic marker for disease mapping. POAG is a complex disease, and a single gene could not be responsible. Understanding the role of genetic polymorphisms, like TNF alpha, could be a prediction of the disease and useful for developing new treatments for POAG.