Detection of multiple sclerosis from exhaled breath using bilayers of polycyclic aromatic hydrocarbons and single-wall carbon nanotubes

A cross-reactive array of polycyclic aromatic hydrocarbons and single wall carbon nanotube bilayers was designed for the detection of volatile organic compounds (tentatively, hexanal and 5-methyl-undecane) that identify the presence of disease in the exhaled breath of patients with multiple sclerosis. The sensors showed excellent discrimination between hexanal, 5-methyl-undecane, and other confounding volatile organic compounds. Results obtained from a clinical study consisting of 51 volunteers showed that the sensors could discriminate between multiple sclerosis and healthy states from exhaled breath samples with 85.3% sensitivity, 70.6% specificity, and 80.4% accuracy. These results open new frontiers in the development of a fast, noninvasive, and inexpensive medical diagnostic tool for the detection and identification of multiple sclerosis. The results could serve also as a launching pad for the discrimination between different subphases or stages of multiple sclerosis as well as for the identification of multiple sclerosis patients who would respond well to immunotherapy.     

Photosynthetic electron partitioning between [FeFe]-hydrogenase and ferredoxin:NADP+-oxidoreductase (FNR) enzymes in vitro

Photosynthetic water splitting, coupled to hydrogenase-catalyzed hydrogen production, is considered a promising clean, renewable source of energy. It is widely accepted that the oxygen sensitivity of hydrogen production, combined with competition between hydrogenases and NADPH-dependent carbon dioxide fixation are the main limitations for its commercialization. Here we provide evidence that, under the anaerobic conditions that support hydrogen production, there is a significant loss of photosynthetic electrons toward NADPH production in vitro. To elucidate the basis for competition, we bioengineered a ferredoxin-hydrogenase fusion and characterized hydrogen production kinetics in the presence of Fd, ferredoxin:NADP(+)-oxidoreductase (FNR), and NADP(+). Replacing the hydrogenase with a ferredoxin-hydrogenase fusion switched the bias of electron transfer from FNR to hydrogenase and resulted in an increased rate of hydrogen photoproduction. These results suggest a new direction for improvement of biohydrogen production and a means to further resolve the mechanisms that control partitioning of photosynthetic electron transport.     

Functional MR imaging during hypercapnia and hyperoxia: noninvasive tool for monitoring changes in liver perfusion and hemodynamics in a rat model

PURPOSE: To prospectively assess functional magnetic resonance (MR) imaging during hypercapnia and hyperoxia for monitoring changes in liver perfusion and hemodynamics in rats. MATERIALS AND METHODS: All experiments were performed with approval of an animal care and use committee. Functional T2*-weighted gradient-echo MR images of the rat liver were acquired during hyperoxia and graded hypercapnia (n=24). Additional images were acquired during portal vein ligation (n=4), induced hypovolemia (n=5), and 70% hepatectomy (n=5). Hypercapnic effects were confirmed with Doppler ultrasonography and with gadopentetate dimeglumine. Differences between groups were analyzed by using Wilcoxon rank sum test, except for the graded hypercapnia, for which one-way analysis of variance was used. RESULTS: Liver signal intensity (SI) increased due to hyperoxia; the percentage change in SI was seven times greater than that in muscle tissue; this reflects higher vascularity of the liver. Liver SI decreased due to hypercapnia; the percentage change in SI was negative in the liver but positive in the muscle (P<.001). Induced hypovolemia resulted in considerable decreases in functional MR imaging response; this reflects lower liver perfusion. Clinical applicability of the functional MR imaging method was proved by monitoring changes in liver perfusion that resulted from liver resection. CONCLUSION: In the liver, the magnitude of the percentage change in SI induced by hypercapnia and hyperoxia reflects changes in total blood volume; whereas percentage change in SI values induced by hypercapnia from a negative to a positive value reflects relative changes in portal-to-arterial blood flow ratio.     

Topical application of drugs influencing cytoskeleton and cell contractility affects alveolar bone loss in rats

BACKGROUND: Several studies have shown that sectioning bundles of collagen fibers in the marginal gingiva during surgical procedures in animals is a distinct stimulus for alveolar bone resorption. Normally, gingival and periodontal fibroblasts, which reside on these collagen fibers, create physiological traction forces generated by the cytoskeleton. By splitting the fibers, traction forces are released, inducing changes in the cytoskeleton and cell shape. In this study, four drugs were selected, including cytochalasin D, EDTA, sodium orthovanadate, and H-7, all influencing the cytoskeleton-integrin-extracellular matrix (ECM) pathway, for their ability to reduce alveolar bone loss by local application. METHODS: The drugs were applied locally only once at the site of mucoperiosteal flap surgery in a rat model. Cytochalasin D (1 microl/microl), EDTA (0.24 mg/microl), sodium orthovanadate (0.02 mg/microl), and H-7 (0.10 microl/microl), each separately, were carried by a protective paste and placed immediately after elevating the flap. The analysis of alveolar bone loss was performed 3 weeks after surgery by scanning the microradiographic films of the mandible cross-sections. The percentages of cross sections with no, moderate, or severe bone loss in treated in comparison to non-treated rats are presented. RESULTS: EDTA, sodium orthovanadate, and H-7 were significantly effective in reducing alveolar bone loss. They were effective in reducing the amount of severe bone loss by 53%, 20%, and 58% while increasing the number of sections with no bone loss by 25%, 23%, and 35%, respectively. Cytochalasin D reduced alveolar bone loss insignificantly. CONCLUSION: EDTA, sodium orthovanadate, and H-7 are effective in reducing alveolar bone loss in rats following mucoperiosteum surgery.     

Ocular injuries following sulfur mustard exposure—Pathological mechanism and potential therapy

Sulfur mustard (SM) is a potent vesicant, known for its ability to cause incapacitation and prolonged injuries to the eyes, skin and respiratory system. The toxic ocular events following sulfur mustard exposure are characterized by several stages: photophobia starting a few hours after exposure, an acute injury phase characterized by inflammation of the anterior segment and corneal erosions and a delayed phase appearing following a clinically silent period (years in human). The late injury appeared in part of the exposed eyes, expressed by epithelial defects and corneal neovascularization (NV), that lead to vision deficits and even blindness. During the last years we have characterized the temporal development of ocular lesions following SM vapor exposure in rabbits and have shown the existence of two sub-populations of corneas, those exhibiting delayed ocular lesions (clinically impaired) and those exhibiting only minor injuries if at all (clinically non-impaired). The aim of the present study was to investigate the pathological mechanism underlying the delayed injury by focusing on the unique characteristics of each sub-population and to test the efficacy of potential treatments.     

Clinical relevance of the nutcracker esophagus: suggested revision of criteria for diagnosis

BACKGROUND: Nutcracker esophagus (NE) is a manometric finding defined by peristaltic contractions with a mean distal esophageal amplitude (DEA) >180 mm Hg. This threshold has been selected as it exceeds the average DEA in healthy volunteers by 2 SDs. Since its introduction the clinical significance of this finding has been challenged, as many patients with NE are asymptomatic. AIM: To evaluate whether defining NE based on a different DEA threshold would be clinically more meaningful. METHODS: Retrospective review of prospectively collected manometry data between October 2001 and December 2003. Using previously published normal DEA values (mean and SD) patients with NE were stratified into 3 groups: group A (2 to 3 SD above mean): DEA 180 to 220 mm Hg; group B (3 to 4 SD above mean): DEA 220 to 260 mm Hg; and group C (>4 SD above mean): DEA >260 mm Hg. Symptoms, esophageal acid exposure, bolus transit data, and lower esophageal sphincter data were reviewed. RESULTS: The stratification of 56 NE patients into groups A, B, and C were 31, 16, and 9, respectively. The proportion of patients presenting with chest pain increased from 23% in group A to 69% in group B and 100% in group C. Patients in group C had significantly (P<0.05) higher mean lower esophageal sphincter pressure, shorter bolus transit time, and lower frequency of abnormal reflux. CONCLUSIONS: A revised definition of NE to include patients with a DEA >260 mm Hg, and possibly those with >220 may have greater clinical relevance.