High-throughput detection of prostate cancer in histological sections using probabilistic pairwise Markov models

In this paper we present a high-throughput system for detecting regions of carcinoma of the prostate (CaP) in HSs from radical prostatectomies (RPs) using probabilistic pairwise Markov models (PPMMs), a novel type of Markov random field (MRF). At diagnostic resolution a digitized HS can contain 80 K × 70 K pixels — far too many for current automated Gleason grading algorithms to process. However, grading can be separated into two distinct steps: (1) detecting cancerous regions and (2) then grading these regions. The detection step does not require diagnostic resolution and can be performed much more quickly. Thus, we introduce a CaP detection system capable of analyzing an entire digitized whole-mount HS (2 × 1.75 cm²) in under three minutes (on a desktop computer) while achieving a CaP detection sensitivity and specificity of 0.87 and 0.90, respectively. We obtain this high-throughput by tailoring the system to analyze the HSs at low resolution (8 μm per pixel). This motivates the following algorithm: (Step 1) glands are segmented, (Step 2) the segmented glands are classified as malignant or benign, and (Step 3) the malignant glands are consolidated into continuous regions. The classification of individual glands leverages two features: gland size and the tendency for proximate glands to share the same class. The latter feature describes a spatial dependency which we model using a Markov prior. Typically, Markov priors are expressed as the product of potential functions. Unfortunately, potential functions are mathematical abstractions, and constructing priors through their selection becomes an ad hoc procedure, resulting in simplistic models such as the Potts. Addressing this problem, we introduce PPMMs which formulate priors in terms of probability density functions, allowing the creation of more sophisticated models. To demonstrate the efficacy of our CaP detection system and assess the advantages of using a PPMM prior instead of the Potts, we alternately incorporate both priors into our algorithm and rigorously evaluate system performance, extracting statistics from over 6000 simulations run across 40 RP specimens. Perhaps the most indicative result is as follows: at a CaP sensitivity of 0.87 the accompanying false positive rates of the system when alternately employing the PPMM and Potts priors are 0.10 and 0.20, respectively.     

Role of NF-E2-related factor 2 in neuroprotective effect of l-carnitine against high glucose-induced oxidative stress in the retinal ganglion cells

l-Carnitine (LC) has protective effects on high glucose-induced oxidative stress in the retinal ganglion cells (RGCs). The aim of this study was to investigate the role of NF-E2-related factor 2 (Nrf2), Kelch like-ECH-associated protein 1 (Keap1), haemoxygenase-1 (HO-1) and γ-glutamyl cysteine synthetase (γ-GCS) in the protective effect of LC on RGCs. RGCs were first processed with high concentrations of glucose. LC treatment at three concentrations (50 μM, 100 μM and 200 μM) was applied to high glucose stimulated RGCs. The expression of Nrf2, Keap1, haemoxygenase-1 (HO-1) and γ-glutamyl cysteine synthetase (γ-GCS) was quantified by Western blot in the treatment and control (high glucose stimulation) groups. In the three LC groups (50 μM, 100 μM and 200 μM), Nrf-2 (0.71 ± 0.04, 0.89 ± 0.05, 1.24 ± 0.05 vs 0.56 ± 0.03, p < 0.05), HO-1 (0.58 ± 0.04, 0.76 ± 0.06, 0.89 ± 0.07 vs 0.25 ± 0.03, p < 0.01), and γ-GCS protein expression (0.66 ± 0.03, 0.79 ± 0.05, 0.84 ± 0.08 vs 0.84 ± 0.08, p < 0.01) was higher than in the control group. The levels of Keap1 protein were in the LC groups were lower than in the control group (0.50 ± 0.03, 0.45 ± 0.02, 0.53 ± 0.03 vs 0.86 ± 0.05, p < 0.01). In conclusion, in high glucose stimulated RGCs, LC treatment was associated with an increased level of Nrf2, HO-1and γ-GCS. LC treatment was also associated with a reduced expression of Keap1 protein. These results suggest that the protective effect of LC treatment on RGCs may be related to Nrf2-Keap1 pathway.     

Tilting for perfusion: Head-up position during cardiopulmonary resuscitation improves brain flow in a porcine model of cardiac arrest

IntroductionCerebral perfusion is compromised during cardiopulmonary resuscitation (CPR). We hypothesized that beneficial effects of gravity on the venous circulation during CPR performed in the head-up tilt (HUT) position would improve cerebral perfusion compared with supine or head-down tilt (HDT).MethodsTwenty-two pigs were sedated, intubated, anesthetized, paralyzed and placed on a tilt table. After 6 min of untreated ventricular fibrillation (VF) CPR was performed on 14 pigs for 3 min with an automated CPR device called LUCAS (L) plus an impedance threshold device (ITD), followed by 5 min of L-CPR + ITD at 0° supine, 5 min at 30° HUT, and then 5 min at 30° HDT. Microspheres were used to measure organ blood flow in 8 pigs. L-CPR + ITD was performed on 8 additional pigs at 0°, 20°, 30°, 40°, and 50° HUT.ResultsCoronary perfusion pressure was 19 ± 2 mmHg at 0° vs. 30 ± 3 at 30° HUT (p < 0.001) and 10 ± 3 at 30° HDT (p < 0.001). Cerebral perfusion pressure was 19 ± 3 at 0° vs. 35 ± 3 at 30° HUT (p < 0.001) and 4 ± 4 at 30° HDT (p < 0.001). Brain–blood flow was 0.19 ± 0.04 ml min⁻¹ g⁻¹ at 0° vs. 0.27 ± 0.04 at 30° HUT (p = 0.01) and 0.14 ± 0.06 at 30° HDT (p = 0.16). Heart blood flow was not significantly different between interventions. With 0, 10, 20, 30, 40 and 50° HUT, ICP values were 21 ± 2, 16 ± 2, 10 ± 2, 5 ± 2, 0 ± 2, −5 ± 2 respectively, (p < 0.001), CerPP increased linearly (p = 0.001), and CPP remained constant.ConclusionDuring CPR, HDT decreased brain flow whereas HUT significantly lowered ICP and improved cerebral perfusion. Further studies are warranted to explore this new resuscitation concept.     

An optimised framework for reconstructing and processing MR phase images

Phase contrast imaging holds great potential for in vivo biodistribution studies of paramagnetic molecules and materials. However, in vivo quantification of iron storage and other paramagnetic materials requires improvements in reconstruction and processing of MR complex images. To achieve this, we have developed a framework including (i) an optimal coil sensitivity smoothing filter for phase imaging determined at the maximal signal to noise ratio, (ii) a phase optimised and a complex image optimised reconstruction approach, and (iii) a magnitude and phase correlation test criterion to determine the low pass filter parameter for background phase removal. The method has been evaluated using 3T and 7T MRI data containing cortical regions, the basal ganglia including the caudate, and the midbrain including the substantia nigra. The optimised reconstruction improves phase image contrast and noise suppression compared with conventional reconstruction approaches, and the correlation test criterion provides an objective method for separation of the local phase signal from the background phase measurements. Phase values of several brain regions of interest have been calculated, including gray matter (? 1.23 Hz at 7T and ? 0.55 Hz at 3T), caudate (? 3.8 Hz at 7T), and the substantia nigra (? 6.2 Hz at 7T).     

Diagnostic value of contrast-enhanced ultrasonography in the characterization of ovarian tumors

IntroductionVascularity influences the characteristics of gynecologic tumors observed with direct imaging techniques that reveal the macrovascular component of these lesions (color and power Doppler) and with indirect imaging involving the administration of contrast agents to examine the microcirculation and interstitial perfusion (contrast-enhanced computed tomography [CT] and magnetic resonance [MR] imaging). The purpose of this study was to determine whether contrast-enhanced ultrasonography (CEUS) of ovarian lesions provides useful information that cannot be obtained with conventional US.Materials and methodsWe used CEUS to assess 72 nonspecific adnexal lesions in 61 patients. CEUS was performed with a 4.8-ml bolus of a second-generation ultrasonographic contrast agent and dedicated imaging algorithms. For each lesion, B-mode morphology, CEUS morphology, and time/intensity curves were evaluated.ResultsIn 8/61 cases (13.1%) CEUS offered no additional morphovascular information. In 38/61 cases (62.3%), it provided additional information that did not modify the management of the lesion, and in 15/61 cases (24.6%) it gave additional information that modified the management of the lesion. Malignant lesions were characterized by significantly shorter times to peak enhancement (11.9 ± 3.1 s vs 19.8 ± 4.0 s p < 0.01) and significantly higher peak intensity (24.7 ± 4.2 dB vs 17.8 ± 3.3 dB p < 0.01) compared with benign lesions.ConclusionsCEUS improves diagnostic confidence in the characterization of liquid-corpuscular lesions where conventional US is inconclusive. CEUS can be proposed as a valid alternative to CT and MR. However, information obtained by CEUS influences the therapy in a limited percentage of cases (24.6%).     

A ventilation technique for oxygenation and carbon dioxide elimination in CPR: Continuous insufflation of oxygen at three levels of pressure in a pig model

AimPulmonary ventilation remains an important part of cardiopulmonary resuscitation, affecting gas exchange and haemodynamics. We designed and studied an improved method of ventilation for CPR, constructed specifically to support both gas exchange and haemodynamics. This method uses continuous insufflation of oxygen at three levels of pressure, resulting in tri-level pressure ventilation (TLPV). We hypothesized that TLPV improves gas exchange and haemodynamics compared to manual gold standard ventilation (GSV).MethodsIn 14 pigs, ventricular fibrillation was induced and automated CPR performed for 10 min with either TLPV or GSV. After defibrillation, CPR was repeated with the other ventilation method. Gas exchange and haemodynamics were monitored. Data are presented as mean ± standard error of the mean.ResultsTLPV was superior to GSV for PaO₂ (163 ± 36 mmHg difference; P = 0.001), and peak AWP (−20 ± 2 cmH₂O difference; P = 0.000) and higher for mean AWP (8 ± 0.2 cmH₂O difference; P = 0.000). TLPV was comparable to GSV for CPP (5 ± 3 mmHg difference; P = 0.012), VCO₂ (0.07 ± 0.3 mL/min/kg difference; P = 0.001), SvO₂ (4 ± 3%-point; P = 0.001), mean carotid flow (−0.5 ± 4 mL/min difference; P = 0.016), and pH_a (0.00 ± 0.03 difference; P = 0.002). The PaCO₂ data do not provide a conclusive result (4 ± 4 mmHg difference).ConclusionWe conclude that the ventilation strategy with a tri-level pressure cycle performs comparable to an expert, manual ventilator in an automated-CPR swine model.     

Twenty-four-hour profiles of urinary excretion of calcium,magnesium, phosphorus,urea, and creatinine in healthy prepubertal boys

ObjectivesAvailable data on 24-h urinary solute excretion in healthy children are sparse. We thus documented the daily and overnight variations of urinary electrolytes (calcium, magnesium, and phosphorus), urea, and creatinine in prepubertal (Tanner stage I) boys.Design and methodsNine voluntary healthy prepubertal boys aged 10.8 ± 0.11 years participated in this study. Concentrations of variables were quantified in daytime samples (collected between 07:00 h ± 30 min and 21:00 h ± 30 min) and nighttime samples (collected between 21:00 h ± 30 min and 07:00 h ± 30 min) in spring, during a period of 24-h every 3 h.ResultsSignificant differences were found between daytime and nighttime excretion of calcium (p < 0.05), magnesium (p < 0.001), phosphorus (p < 0.01), and urea (p < 0.05), with high concentrations during the night. The 24-h solute/creatinine ratio was 0.072 ± 0.008 mg/mg for calcium, 0.069 ± 0.008 mg/mg for magnesium, 0.698 ± 0.070 mg/mg for phosphorus, and 0.017 ± 0.001 g/mg for urea. Statistically significant correlation analyses showed that urea and creatinine were positively associated with body mass index (BMI) (R = 0.790, p = 0.0113 for urea; R = 0.889, p = <0.0013 for creatinine) and weight (R = 0.717, p = 0.0297 for urea; R = 0.978, p = < 0.001 for creatinine). The other urinary variables were independent of BMI and body mass.ConclusionThese data are of interest for the diagnosis of certain renal disease in prepubertal children.     

Comparison of the effects of lidocaine pre-administration and local warming of the intravenous access site on propofol injection pain: Randomized,double-blind controlled trial

BackgroundLidocaine reduces pain that occurs upon the intravenous injection of propofol. But, there are few non-pharmacological nursing interventions to reduce propofol injection pain.ObjectiveTo compare the effects of lidocaine pre-administration and local warming of the intravenous access site on propofol injection pain.DesignProspective, double-blind, randomized controlled trial.SettingThe 555 bed, non-teaching National Cancer Center in Kyunggido, South Korea.ParticipantsA total of 96 patients who underwent thyroidectomy under total intravenous general anesthesia with propofol were randomly allocated to the control, lidocaine pre-administration (LA) or local warming (LW) group.MethodsAll three groups received 2% propofol with an effect-site target at 3 μg/mL for induction dose. The control group received 2% propofol with no intervention. The lidocaine pre-administration group received 2% propofol 30 s after 1% lidocaine 30 mg. The local warming group received 2% propofol after warming of the intravenous access site for 1 min using 43 °C forced air. Propofol injection pain was assessed by four-point verbal categorial scoring (VCS), numerical rating scale (NRS) and surgical pleth index (SPI).ResultsPain VCS of the LA group (mean ± SD, 1.11 ± 0.45) was significantly reduced (U = −3.92, p < .001) compared to the control group (mean ± SD, 1.71 ± 0.74). Pain VCS of the LW group (mean ± SD, 0.76 ± 0.44) was significantly reduced (U = −5.17, p < .001) compared to the control group (mean ± SD, 1.71 ± 0.74). Pain VCS of the LW group was significantly reduced compared to the LA group (U = −3.33, p = .001]. Pain NRS of the LA group (mean ± SD, 4.31 ± 2.32) was significantly reduced (mean difference, 1.82; 95% CI, 0.63–3.00; p = .003) compared to the control group (mean ± SD, 6.13 ± 2.39). Pain NRS of the LW group (mean ± SD, 3.06 ± 2.37) was significantly reduced (mean difference, 3.07; 95% CI, 1.63–4.51; p < .009) compared to the control group. There were significant differences in pain NRS between the LA group and the LW group (mean difference, 1.25; 95% CI, 0.09–2.42; p = .035). SPI of the LA group (mean ± SD, 64.1 ± 16.3) was significantly reduced (mean difference control versus LA, 8.36; 95% CI, 1.64–15.1; p = .016) compared to the control group (mean ± SD, 72.5 ± 9.56). SPI of the LW group (mean ± SD, 55.0 ± 16.2) was significantly reduced (mean difference control versus LW, 17.4; 95% CI, 10.8–24.0; p < .001) compared to the control group. There was a significant difference in SPI between the LA group and LW group (mean difference, 9.06; 95% CI, 1.02–17.1; p = .028).ConclusionLocal warming of the intravenous access site by 43 °C forced air for 1 min is slightly more effective in reducing propofol injection pain compared to lidocaine pre-administration.     

Effect of implementation of new resuscitation guidelines on quality of cardiopulmonary resuscitation and survival

BackgroundDuring cardiopulmonary resuscitation (CPR), advanced life support (ALS) providers have been shown to deliver inadequate CPR with long intervals without chest compressions. Several changes made to the 2005 CPR Guidelines were intended to reduce unnecessary interruptions. We have evaluated if quality of CPR performed by the Oslo Emergency Medical System (EMS) improved after implementation of the modified 2005 CPR Guidelines, and if any such improvement would result in increased survival.Materials and methodsRetrospective, observational study of all consecutive adult cardiac arrest patients treated during a 2-year period before (May 2003–April 2005), and after (January 2006–December 2007) implementation of the modified 2005 CPR Guidelines. CPR quality was assessed from continuous electronic recordings from LIFEPACK 12 defibrillators where ventilations and chest compressions were identified from transthoracic impedance changes. Ambulance run sheets, Utstein forms and hospital records were collected and outcome evaluated.ResultsResuscitation was attempted in 435 patients before and 481 patients after implementation of the modified 2005 CPR Guidelines. ECGs usable for CPR quality evaluation were obtained in 64% and 76% of the cases, respectively. Pre-shock pauses decreased from median (interquartile range) 17 s (11, 22) to 5 s (2, 17) (p = 0.000), overall hands-off ratios from 0.23 ± 0.13 to 0.14 ± 0.09 (p = 0.000), compression rates from 120 ± 9 to 115 ± 10 (p = 0.000) and ventilation rates from 12 ± 4 to 10 ± 4 (p = 0.000). Overall survival to hospital discharge was 11% and 13% (p = 0.287), respectively.ConclusionQuality of CPR improved after implementation of the modified 2005 Guidelines with only a weak trend towards improved survival to hospital discharge.     

Enhanced levels of soluble and membrane-bound CD137 levels in patients with acute coronary syndromes

BackgroundIncreasing evidence shows that costimulatory molecules of the tumor necrosis factor superfamily such as CD40/CD40 ligand and OX40/OX40 ligand have been implicated in atherosclerosis. We investigated whether the expression levels of the tumor necrosis factor superfamily members CD137 in serum and membrane-bound were related to acute coronary syndromes (ACS).MethodsThirty normal controls and 210 patients, including 70 with stable angina (SA), 80 with unstable angina (UA), and 60 with acute myocardial infarction (AMI), were enrolled in our study. The expression of CD137 in peripheral monocytes was analyzed by flow cytometry. Serum soluble CD137 (sCD137) and C-reactive protein levels were measured by commercially available ELISA.ResultsThe expression of CD137 in peripheral monocytes in patients with UA [14.2 ± 3.5 mean fluorescence intensity (MFI)] and AMI (15.1 ± 4.4 MFI) was significantly higher than those in patients with SA (6.5±2.4 MFI) and controls (7.1 ± 3.5 MFI). sCD137 in patients with UA (16.7 ± 4.9 ng/ml) and AMI (19.1 ± 4.3 ng/ml) were significantly higher than those in patients with SA (3.4 ± 1.4 ng/ml) and controls (3.9 ± 1.3 ng/ml) (p < 0.001). C-reactive protein level in serum in patients with UA (13.8 ± 3.3 ng/ml) and AMI (15.5 ± 4.7 ng/ml) were also higher than those in patients with SA (1.4 ± 0.4 ng/ml) and controls (1.3 ± 0.3 ng/ml). It was interesting that percutaneous transluminal coronary angioplasty (PTCA) induced a marked rise in sCD137 levels in SA patients, while CD137 expression in peripheral monocytes showed no difference between SA patients with PTCA before and after. A positive correlation was found between sCD137 and serum C-reactive protein levels (r = 0.681; p < 0.0001).ConclusionPatients with ACS showed increased soluble and membrane-bound CD137 expression. sCD137 level showed a significantly positive correlation with CRP level in patients with ACS. The relation between sCD137 and ACS needs further researches.     

Enhanced cortical reperfusion protects coagulation factor XII-deficient mice from ischemic stroke as revealed by high-field MRI

Intrinsic coagulation factor XII deficient (FXII^?/?) mice are protected from ischemic stroke. To elucidate underlying mechanisms we investigated the early ischemic period in vivo by multimodal magnetic resonance imaging (MRI) at 17.6 Tesla.Cerebral ischemia was induced by either transient (60 min) or permanent occlusion of the middle cerebral artery (t/pMCAO). 10 FXII^?/? mice underwent t- , 10 FXII^?/? mice p- and 10 Wildtype (Wt) mice tMCAO. Cerebral blood flow (CBF), diffusion-weighted-imaging (DWI) and T2-relaxometry were measured at 2 h and 24 h after MCAO. Outcome measures were evaluated after motion correction and normalization to atlas space. 2 h after tMCAO CBF reduction was similar in FXII^?/? and Wt mice extending over cortical (CBF (ml/100 g/min) 33.6 ± 6.9 vs. 35.3 ± 4.6, p = 0.42) and subcortical regions (25.7 ± 4.5 vs. 31.6 ± 4.0, p = 0.17). At 24 h, recovery of cortical CBF by +36% was observed only in tMCAO FXII^?/? mice contrasting a further decrease of – 30% in Wt mice after tMCAO (p = 0.02, F_(1,18) = 6.24). In FXII^?/? mice in which patency of the MCA was not restored (pMCAO) a further decrease of ? 75% was observed. Cortical reperfusion in tMCAO FXII^?/? mice was related to a lower risk of infarction of 59% vs. 93% in Wt mice (p = 0.04). Subcortical CBF was similarly decreased in both tMCAO groups (Wt and FXII^?/?) relating to a similar risk of infarction of 89% (Wt) vs. 99% (FXII^?/?, p = 0.17).Deficiency of FXII allows neocortical reperfusion after tMCAO and rescues brain tissue by this mechanism. This study supports the concept of FXII as a promising new target for stroke prevention and therapy.     

Optimal region of the putamen for image-guided convection-enhanced delivery of therapeutics in human and non-human primates

Optimal results in the direct brain delivery of brain therapeutics such as growth factors or viral vector into primate brain depend on reproducible distribution throughout the target region. In the present study, we retrospectively analyzed MRI of 25 convection-enhanced delivery (CED) infusions with MRI contrast into the putamen of non-human primates (NHP). Infused volume (V_i) was compared to total volume of distribution (V_d) versus V_d within the target putamen. Excellent distribution of contrast agent within the putamen was obtained in eight cases that were used to define an optimal target volume or “green” zone. Partial or poor distribution with leakage into adjacent anatomical structures was noted in 17 cases, defining “blue” and “red” zones, respectively. Quantitative containment (99 ± 1%) of infused gadoteridol within the putamen was obtained when the cannula was placed in the green zone, 87 ± 3% in the blue zone and 49 ± 0.05% in the red zone. These results were used to determine a set of 3D stereotactic coordinates that define an optimal site for putaminal infusions in NHP and human putamen. We conclude that cannula placement and definition of optimal (green zone) stereotactic coordinates have important implications in ensuring effective delivery of therapeutics into the putamen utilizing routine stereotactic MRI localization procedures and should be considered when local therapies such as gene transfer or protein administration are being translated into clinical therapy.     

Proatherogenic disturbances in lipoprotein profile,associated enzymes and transfer proteins in women with iron deficiency anaemia

ObjectiveTo characterize the lipid-related atherogenic risk factors in iron deficiency anaemia (IDA) patients.Design and methodsTwenty IDA women were compared to healthy age-matched controls. Lipoprotein profile, cholesteryl ester transfer protein (CETP), paraoxonase (PON) 1 and lipoprotein-associated phospholipase A₂ (LpPLA₂) activities and plasma levels of oxidized-LDL were evaluated.ResultsTriglycerides were higher (median [range]) (1.0 [0.5–1.9] vs. 0.7 [0.5–1.5] mmol/L, p < 0.05) and HDL-C lower (mean ± SD) (1.3 ± 0.3 vs. 1.6 ± 0.4 mmol/L, p < 0.01) in the patients group. CETP (197 ± 29% vs. 151 ± 29% mL^? 1 h^? 1, p < 0.001), PON 1 (122 ± 17 vs. 140 ± 33 μmol mL^? 1 min^? 1, p < 0.05) and LpPLA₂ (9.6 ± 2.0 vs. 8.1 ± 1.7 μmol mL^? 1 h^? 1, p < 0.05) activities were different in IDA women. No difference was observed in oxidized-LDL. Haemoglobin correlated negatively with triglycerides (r = ? 0.35, p < 0.05), CETP (r =  ?  0.62, p < 0.001) and LpPLA₂ (r =  ?  0.34, p < 0.05), while ferritin was positively associated with HDL-C (r =  0.39, p < 0.05) and inversely with CETP (r =  ?  0.49, p < 0.005).ConclusionThe alterations in lipoprotein profile, CETP, PON 1 and LpPLA₂ activities described in the present study indicate that non-treated IDA might represent a proatherogenic state.     

Comparison of changes in abdominal muscle thickness between standing and crook lying during active abdominal hollowing using ultrasound imaging

To determine if transversus abdominis (TrA) demonstrates a greater increase in thickness on lower abdominal hollowing (LAH) in standing compared to crook lying.Muscle thickness measurements of TrA, addition of internal obliques (IO) and external obliques (EO) were measured using ultrasound imaging at rest and during LAH on 28 healthy controls (14 female, 14 male) in crook lying and standing.TrA demonstrated greater thickness changes on LAH in standing (+0.88 mm ± 0.12 mm). IO and EO demonstrated greater thickness changes on LAH in crook lying (+0.59 mm ± 0.08 mm and ?0.87 mm ± 0.12 mm, respectively). These differences were all significant (p < 0.001). Increased resting thickness was noted in standing in TrA (20.7%), IO (10.3%) and EO (1.2%). This increase was only significantly different between TrA and EO (P = 0.004).TrA showed significantly greater increases in thickness on LAH in standing compared to crook lying, and with greater specificity in relation to IO and maybe EO. If muscle thickness can be an indicator of muscle function or activity, then this suggests that TrA rehabilitation should be facilitated in positions of greater function, such as standing.     

Amelioratory effect of flavonoids rich Pergularia daemia extract against CFA induced arthritic rats

PurposePergularia daemia Forsk. (Asclepiadaceae) is a traditionally reported medicinal herb used to treat joint pain and arthritis. However, there are no scientific reports about anti-arthritic activity of P. daemia methanolic extract on rats as animal model. This study identifies bioactive compounds present in the P. daemia methanolic extract and evaluates its anti-arthritic potential in CFA induced arthritic rats.Methods and resultsPhytoconstituents of P. daemia extract were examined using LC-ESI/MS method. Anti-arthritic activity of P. daemia extract was determined by various biochemical experiments (RF, ESR and CRP), ultrasonography and histological analysis. LC-ESI/MS analysis resulted in the identification of major flavonoids compounds such as formononetin, qurecetin, chrysoeriol, taxifolin and naringenin. Serum biomarker analysis, after the treatment with PDME (500 mg/kg b.w.) revealed that the hemoglobin (11.84 ± 0.42 g/dL) and RBC (8.38 ± 0.67 million/mm³) levels were significantly increased whereas WBC (8.91 ± 0.38 thousands/mm³), RF (17.94 ± 0.45 IU/mL), ESR (7.91 ± 0.12 mm/h) and CRP (22.56 ± 0.26 mg/L) levels were decreased when compared with the CFA induced arthritic control group. Histology results revealed that treatment with PDME has resulted in significant prevention against bony destruction by decreasing soft tissue swelling and narrowing of joint spaces (250 and 500 mg/kg b.w.).ConclusionAnti-arthritic effect of P. daemia might be due to the presence of these bioactive flavonoids. These findings lend pharmacological support to the reported folkloric use of P. daemia in the treatment and management of painful, arthritic inflammatory conditions.     

The effect of sodium bicarbonate on cytokine secretion in CKD patients with metabolic acidosis

The incidence of acidosis increases with the progression of chronic kidney disease (CKD). Correction of acidosis by sodium bicarbonate may slow CKD deterioration. Inflammation, which is common in CKD, may be related to acidosis. Whether the slower rate of GFR decline following the correction of acidosis is related to changes in inflammatory markers is unknown. The current study examined whether correcting CKD-acidosis affected inflammatory cytokines secretion. Thirteen patients with CKD 4–5 and acidosis were tested for cytokines secretion from peripheral-blood mononuclear cells at baseline and after one month of oral sodium bicarbonate. Following treatment with sodium bicarbonate there was no change in weight, blood pressure, serum creatinine, albumin, sodium, calcium, phosphate, PTH, hemoglobin and CRP. Serum urea decreased (134 ± 10–116 ± 8 mg/dl, P = 0.002), potassium decreased (5.1 ± 0.4–4.8 ± 0.1 mequiv./l, P = 0.064), pH increased (7.29 ± 0.01–7.33 ± 0.01, P = 0.008), and serum bicarbonate increased (18.6 ± 0.4 mequiv./l to 21.3 ± 0.3 mequiv./l, P = 0.001). The secretion of the anti-inflammatory cytokine IL-10 decreased (2.75 ± 0.25 ng/ml to 2.29 ± 0.21 ng/ml, P = 0.041). There was no significant change in the secretion of the other pro-inflammatory and anti-inflammatory cytokines, including IL-1β, IL-2, IL-6, TNFα, IFNγ, IL-1ra. Thus, correcting acidosis in CKD with bicarbonate decreases IL-10 secretion. Its significance needs to be further investigated.     

Resting thickness of transversus abdominis is decreased in athletes with longstanding adduction-related groin pain

The purpose of the study was to compare thickness of the transversus abdominis (TA) and obliquus internus (OI) muscles between athletes with and without longstanding adduction-related groin pain (LAGP).Forty two athletes with LAGP and 23 controls were included. Thickness of TA and OI were measured with ultrasound imaging on the right side of the body during rest. Relative muscle thickness (compared to rest) was measured during the active straight leg raise (ASLR) left and right, and during isometric hip adduction.TA resting thickness was significantly smaller in injured subjects with left-sided (4.0 ± 0.82 mm; P < 0.001) or right-sided (4.3 ± 0.64 mm; P = 0.015) groin complaints compared with controls (4.9 ± 0.90 mm). No significant differences between patients and controls in TA or OI relative thickness during the ASLR and isometric hip adduction were found (all cases P ≥ 0.15).In conclusion, TA resting thickness is smaller in athletes with LAGP and may thus be a risk factor for (recurrent) groin injury. This may have implications for therapy and prevention of LAGP.     

Variability of the glycemic response to single food products in healthy subjects

BackgroundMany studies on the health effects of the glycemic index (GI) are confounded by differences in the intakes of other macronutrients and fibre. Little data exist about the within- and between-subject variability of the GI.ObjectiveOur objectives were therefore (i) to calculate the GI of eight commonly used food products with similar macronutrient and fibre composition, but with different sources of carbohydrates, (ii) to examine the inter- and intra-individual variability of the incremental area under the curve (iAUC) after consuming the reference solution, and (iii) to compare the effect of three different methods on 2-h postprandial blood glucose responses.DesignFour groups of 10 healthy subjects consumed in random order the increased (iGI) and decreased GI (dGI) variants and twice a glucose solution. All products consisted of 25 g available carbohydrates (CHO). For the fruit drink, glucose values were simultaneously analyzed using venous and capillary blood samples, and by using a continuous glucose monitoring system (CGMS).ResultsThe GIs for increased and decreased variants were (mean ± standard error of the mean (SEM)) 69 ± 15 and 40 ± 4 for bread, 86 ± 14 and 48 ± 8 for a fruit drink, 51 ± 12 and 20 ± 4 for cake, and 63 ± 17 and 37 ± 10 for a cookie. The inter- and intra-individual coefficient of variation (CV) of the iAUCs of the reference solution was large and varied respectively between 13 and 38%, and between 33 and 80%.ConclusionsThese data suggest that the GI is difficult to use at the individual level.