Breath Formate Is a Marker of Airway S-Nitrosothiol Depletion in Severe Asthma

-nitrosothiols (SNOs), a class of endogenous airway smooth muscle relaxants. This deficiency results from increased activity of an enzyme that both reduces SNOs to ammonia and oxidizes formaldehyde to formic acid, a volatile carboxylic acid that is more easily detected in exhaled breath condensate (EBC) than SNOs. We therefore hypothesize that depletion of airway SNOs is related to asthma pathology, and breath formate concentration may be a proxy measure of SNO catabolism. (r = −0.39, p = 0.002, asthmatics only), and positively correlated with the NO-derived ion nitrite (r = 0.46, p<0.0001) as well as with total serum IgE (r = 0.28, p = 0.016, asthmatics only). Furthermore, formate was not significantly correlated with other volatile organic acids nor with inhaled corticosteroid dose.-nitrosothiols

Evaluation of a combined thiourea and hydrogen peroxide regimen to bleach bloodstained teeth

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Background: Current techniques for intra-coronal bleaching of stained root-filled teeth employ oxidative bleaching with hydrogen peroxide. However, concern over the potential for invasive cervical resorption following the use of hydrogen peroxide has been expressed by many researchers, and recommendations have been made to limit the use of this agent. A reductive-oxidative bleaching process using a thiourea and hydrogen peroxide regimen is proposed as an effective and safer bleaching combination. The efficacy of this novel bleaching regimen is evaluated in this study. Methods: The study involved a quantitative and qualitative spectrophotometric assessment of the ability of two amine (bleaching) agents, aqueous thiourea and acidified thiourea, to alter the absorption spectra of haemoglobin and methaemoglobin compared to hydrogen peroxide. In addition, extracted premolar teeth discoloured by blood were subjected to different bleaching regimens using amine reducing agents and hydrogen peroxide. The change in the colour of the bloodstained dentine samples was measured at each stage of the bleaching process with a Photometer and Reflectance Densitometer. Comparisons of different treatments were made using a method of least significant difference and/or analysis of variance. Results: Spectrophotometric studies showed that acidified thiourea solution greatly reduced the colour of the haemoglobin and methaemoglobin in the visible range (330–760nm). Aqueous thiourea had no effect on the presence of haemoglobin and methaemoglobin. Reflection Densitometer and Photometer scores indicate that the greatest bleaching effect was achieved by the combined acidified thiourea and hydrogen peroxide regimen. Conclusion: The recognition that bleaching discoloured teeth is a chemical process, which can be achieved by both reducing and oxidizing agents, offers the possibility of developing new and safer clinical bleaching protocols. It is concluded that the bleaching regimen which employs the sequential use of 0.1M acidified thiourea and 30% w/v hydrogen peroxide is as effective at bleaching bloodstained dentine as 30% w/v hydrogen peroxide alone. However, the addition of thiourea to the bleaching regimen has the potential benefit of reducing the level of damaging hydroxyl radicals and achieving a safer bleaching process.K. Maiolo, PD Marin, TE Bridges and GS Heithersa

Hospital characteristics and patient populations served by physician owned and non physician owned orthopedic specialty hospitals

<p>Abstract</p> <p>Background</p> <p>The emergence of physician owned specialty hospitals focusing on high margin procedures has generated significant controversy. Yet, it is unclear whether physician owned specialty hospitals differ significantly from non physician owned specialty hospitals and thus merit the additional scrutiny that has been proposed. Our objective was to assess whether physician owned specialty orthopedic hospitals and non physician owned specialty orthopedic hospitals differ with respect to hospital characteristics and patient populations served.</p> <p>Methods</p> <p>We conducted a descriptive study using Medicare data of beneficiaries who underwent total hip replacement (THR) (N = 10,478) and total knee replacement (TKR) (N = 15,312) in 29 physician owned and 8 non physician owned specialty orthopedic hospitals during 1999–2003. We compared hospital characteristics of physician owned and non physician owned specialty hospitals including procedural volumes of major joint replacements (THR and TKR), hospital teaching status, and for profit status. We then compared demographics and prevalence of common comorbid conditions for patients treated in physician owned and non physician owned specialty hospitals. Finally, we examined whether the socio-demographic characteristics of the neighborhoods where physician owned and non physician owned specialty hospitals differed, as measured by zip code level data.</p> <p>Results</p> <p>Physician owned specialty hospitals performed fewer major joint replacements on Medicare beneficiaries in 2003 than non physician owed specialty hospitals (64 vs. 678, P < .001), were less likely to be affiliated with a medical school (6% vs. 43%, P = .05), and were more likely to be for profit (94% vs. 28%, P = .001). Patients who underwent major joint replacement in physician owned specialty hospitals were less likely to be black than patients in non physician owned specialty hospitals (2.5% vs. 3.1% for THR, P = .15; 1.8% vs. 6.3% for TKR, P < .001), yet physician owned specialty hospitals were located in neighborhoods with a higher proportion of black residents (8.2% vs. 6.7%, P = .76). Patients in physician owned hospitals had lower rates of most common comorbid conditions including heart failure and obesity (P < .05 for both).</p> <p>Conclusion</p> <p>Physician owned specialty orthopedic hospitals differ significantly from non physician owned specialty orthopedic hospitals and may warrant the additional scrutiny policy makers have proposed.</p

The ability of thiourea to scavenge hydrogen peroxide and hydroxyl radicals during the intra-coronal bleaching of bloodstained root-filled teeth

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Background: Hydrogen peroxide, an agent used in the intra-coronal bleaching of root-filled teeth for over a century, has been shown to diffuse from the pulp chamber to the outer root surface. Furthermore, it has been demonstrated that destructive hydroxyl radicals, the by-products of the bleaching process, have been detected on the external root surface. The control of such diffusion may be of importance in minimizing the risk of invasive cervical resorption (ICR) which has been linked to intra-coronal bleaching of discoloured root-filled teeth using hydrogen peroxide. The aims of the present in vitro study are to quantify the diffusion of hydrogen peroxide and hydroxyl radicals to the outer root surface following intra-coronal bleaching, and to evaluate the ability of thiourea incorporated into the bleaching protocol to scavenge residual hydrogen peroxide and hydroxyl radicals. Methods: Thirty-five single rooted premolar teeth with intact cementum at the cemento-enamel junction were used in this project. Thirty teeth were stained with red blood cells and root-filled with gutta-percha and AH26. The five unstained teeth were root-filled and constituted a negative control (Group 1). The stained teeth were divided equally into the following experimental groups and subjected to various intra-coronal bleaching regimes: Group 2 – ‘walking bleach’ with 20μl 30 per cent w/w hydrogen peroxide; Group 3 – 20μl 30 per cent w/w hydrogen peroxide and thermocatalytically activated; Group 4 – 20μl acidified thiourea; Group 5 – 20μl acidified thiourea and 20μl 30 per cent w/w hydrogen peroxide; Group 6 – 20μl acidified thiourea and 20μl one per cent sodium hypochlorite; Group 7 – 20μl acidified thiourea, 20μl one per cent sodium hypochlorite and 20μl 30 per cent w/w hydrogen peroxide. The reaction products of the bleaching process were quantified at the outer root surface using high performance liquid chromatography and electrochemical detection (HPLC-ECD).Results: Results showed that hydrogen peroxide used alone in Groups 2 and 3 was able to be detected at the outer root surface in 100 per cent of the samples, and that the presence of the hydroxyl radical generated in both groups was detected in equal amounts (P<0.05). When thiourea was incorporated into the bleaching protocols in Groups 5–7, it was shown to scavenge both hydrogen peroxide and hydroxyl radicals to a significant degree (P<0.05). Conclusions: Acidulated thiourea is an effective scavenger of residual hydrogen peroxide and hydroxyl radicals generated during the intra-coronal bleaching of bloodstained root-filled teeth.DS Farmer, P Burcham, PD Mari

Cerebrospinal fluid matrix metalloproteinase-9 increases during treatment of recurrent malignant gliomas

<p>Abstract</p> <p>Background</p> <p>Matrix metalloproteinases (MMPs) are enzymes that promote tumor invasion and angiogenesis by enzymatically remodeling the extracellular matrix. MMP-2 and MMP-9 are the most abundant forms of MMPs in malignant gliomas, while a 130 kDa MMP is thought to be MMP-9 complexed to other proteinases. This study determined whether doxycycline can block MMP activity <it>in vitro</it>. We also measured MMP-2 and MMP-9 levels in cerebrospinal fluid (CSF) from patients with recurrent malignant gliomas.</p> <p>Methods</p> <p>To determine whether doxycycline can block MMP activity, we measured the extent of doxycyline-mediated MMP-2 and MMP-9 inhibition <it>in vitro </it>using epidermal growth factor receptor (EGFR) transfected U251 glioma cell lines. MMP activity was measured using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) zymography. In addition, patients underwent lumbar puncture for CSF sampling at baseline, after 6 weeks (1 cycle), and after 12 weeks (2 cycles), while being treated with a novel chemotherapy regimen of irinotecan, thalidomide, and doxycycline designed to block growth/proliferation, angiogenesis, and invasion. Irinotecan was given at 125 mg/m²/week for 4 weeks in 6-week cycles, together with continuous doxycycline at 100 mg twice daily on Day 1 and 50 mg twice daily thereafter. Daily thalidomide dose in our cohort was 400 mg. Tumor progression was monitored by magnetic resonance imaging (MRI).</p> <p>Results</p> <p>Doxycyline <it>in vitro </it>completely abolished MMP-9 activity at 500 μg/ml while there was only 30 to 50% inhibition of MMP-2 activity. Four patients respectively completed 4, 3, 1, and 2 cycles of irinotecan, thalidomide, and doxycycline. Patient enrollment was terminated after one patient developed radiologically defined pulmonary embolism, and another had probable pulmonary embolism. Although CSF MMP-2 and 130 kDa MMP levels were stable, MMP-9 level progressively increased during treatment despite stable MRI.</p> <p>Conclusion</p> <p>Doxycycline can block MMP-2 and MMP-9 activities from glioma cells <it>in vitro</it>. Increased CSF MMP-9 activity could be a biomarker of disease activity in patients with malignant gliomas, before any changes are detectable on MRI.</p

Elevated serum matrix metalloproteinase 9 (MMP-9) concentration predicts the presence of colorectal neoplasia in symptomatic patients

Early detection of polyps or colorectal carcinoma can reduce colorectal carcinoma-associated deaths. Previous studies have demonstrated raised serum levels of matrix metalloproteinase 9 (sMMP-9) in a range of cancers. The aim of this study was to investigate the role of sMMP-9 levels in identifying colorectal neoplasia. Consenting patients donated a blood sample and were assessed by proforma-led history and physical examination. Samples were analysed for sMMP-9 concentration (enzyme-linked immuno-sorbant assay) and compared to final diagnoses. Logistic regression modelling determined independent factors associated with neoplasia. A total of 365 patients were recruited of whom 300 were analysed, including 46 normal controls. A total of 27 significant adenomas and 63 malignancies were identified. The median sMMP-9 concentration was 443ng ml−1 (IQR: 219–782; mean: 546). Patients with neoplasia had significantly elevated sMMP-9 levels (P<0.001). Logistic regression modelling identified elevated log(sMMP-9) as the most significant predictor of neoplasia (χ2=38.33, P<0.001). Other significant factors were age, sex, smoking history, abdominal pain and weight loss. The model accurately predicted neoplasia in 77.3% of cases. Sensitivity and specificity were 77.9 and 77.1%. sMMP-9 estimation can accurately stratify patient to low- or high-risk cohorts. Serum sampling is a potential means of avoiding unnecessary colonoscopy and reducing patient anxiety, iatrogenic morbidity and mortality, and cost

Motor expertise modulates the unconscious processing of human body postures

Little is known about the cognitive background of unconscious visuomotor control of complex sports movements. Therefore, we investigated the extent to which novices and skilled high-jump athletes are able to identify visually presented body postures of the high jump unconsciously. We also asked whether or not the manner of processing differs (qualitatively or quantitatively) between these groups as a function of their motor expertise. A priming experiment with not consciously perceivable stimuli was designed to determine whether subliminal priming of movement phases (same vs. different movement phases) or temporal order (i.e. natural vs. reversed movement order) affects target processing. Participants had to decide which phase of the high jump (approach vs. flight phase) a target photograph was taken from. We found a main effect of temporal order for skilled athletes, that is, faster reaction times for prime-target pairs that reflected the natural movement order as opposed to the reversed movement order. This result indicates that temporal-order information pertaining to the domain of expertise plays a critical role in athletes’ perceptual capacities. For novices, data analyses revealed an interaction between temporal order and movement phases. That is, only the reversed movement order of flight-approach pictures increased processing time. Taken together, the results suggest that the structure of cognitive movement representation modulates unconscious processing of movement pictures and points to a functional role of motor representations in visual perception