Properties In Healthy Subjects Research Articles

Left atrial volumes changes are associated with changes in mitral annular dimensions and functional properties in healthy adults – a three-dimensional speckle-tracking echocardiographic study

Abstract Introduction Three-dimensional (3D) speckle-tracking echocardiography (3DSTE) is a novel echocardiographic method with capability of 3D assessment of heart chambers and valvular annuli making an opportunity to compare cyclic changes of left atrial (LA) volumes and mitral annular (MA) dimensions in physiological healthy circumstances. The present study was designed to examine correlations between LA volume changes and MA dimensions and functional properties in healthy adult subjects by 3DSTE. Methods The study population consisted of 199 healthy adults (mean age: 33.5±12.7 years, 104 males), who had no symptoms, conditions or diseases, which could affect results. None of subjects received any medication. The group of subjects was divided according to their maximum LA volume (Vmax) into three groups using 30 ml and 50 ml as cut-off values. All subjects underwent complete two-dimensional Doppler echocardiography extended with 3DSTE. Results All LA volumes and stroke volumes increased with end-systolic Vmax. Early diastolic passive atrial emptying fraction (PAEF) was significantly reduced in patients with Vmax>50 ml. End-systolic total atrial emptying fraction (TAEF) and late diastolic active atrial emptying fraction (AAEF) was not accompanied with increased end-systolic Vmax. Both end-diastolic and end-systolic MA dimensions were dilated in subjects with increased Vmax, which was accompanied with reduction of MA function. Only end-systolic MA dimensions showed further increase, when end-systolic Vmax was larger than 50 ml compared to cases with Vmax between 30 ml and 50 ml. When prognostic value of MA dimensions and functional properties were analyzed, several MA dimensions and MA fractional area change (MAFAC) were found to have prognostic value to predict Vmax>50 ml. The cut-off values for end-diastolic MA diameter (MAD-D), end-systolic MA diameter (MAD-S) and area, end-diastolic and end-systolic MA perimeter and MAFAC to predict Vmax>50 ml proved to be 2.3 cm, 1.5 cm, 3.4 cm2, 10.2 cm, 7.4 cm and 50.93%, respectively. While increased LA volumes were associated with both dilated MAD-D and MAD-S, only increased diastolic LA volumes were associated with reduced MAFAC. While dilated MAD-D was associated with increased total and active atrial stroke volumes, similar relationship with MAD-S could not be detected. Increased passive atrial stroke volume was associated with augmented MAFAC. While dilated MAD-D was associated with increased AAEF, dilated MAD-S was found to be related to reduced TAEF and PAEF. Increased MAFAC was associated with increased values regarding all emptying fractions. End-diastolic MA dimensions increased with dilation of end-systolic MA dimensions and vice versa. Increased MAFAC was associated with dilated MAD-D and reduced MAD-S. Conclusions Strong relationship exists between LA volumes and MA dimensions and functional properties in healthy subjects. Funding Acknowledgement Type of funding sources: None.

Connectivity Patterns in the Core Resting-State Networks and Their Influence on Cognition.

Introduction: Three prominent resting-state networks (rsNW) (default mode network [DMN], salience network [SN], and central executive network [CEN]) are recognized for their important role in several neuropsychiatric conditions. However, our understanding of their relevance in terms of cognition remains insufficient. Materials and Methods: In response, this study aims at investigating the patterns of different network properties (resting-state activity [RSA] and short- and long-range functional connectivity [FC]) in these three core rsNWs, as well as the dynamics of age-associated changes and their relation to cognitive performance in a sample of healthy controls (N = 74) covering a large age span (20-79 years). Using a whole-network based approach, three measures were calculated from the functional magnetic resonance imaging (fMRI) data: amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), and degree of network centrality (DC). The cognitive test battery covered the following domains: memory, executive functioning, processing speed, attention, and visual perception. Results: For all three fMRI measures (ALFF, ReHo, and DC), the highest values of spontaneous brain activity (ALFF), short- and long-range connectivity (ReHo, DC) were observed in the DMN and the lowest in the SN. Significant age-associated decrease was observed in the DMN for ALFF and DC, and in the SN for ALFF and ReHo. Significant negative partial correlations were observed for working memory and ALFF in all three networks, as well as for additional cognitive parameters and ALFF in CEN. Discussion: Our results show that higher RSA in the three core rsNWs may have an unfavorable effect on cognition. Conversely, the pattern of network properties in healthy subjects included low RSA and FC in the SN. This complements previous research related to the three core rsNW and shows that the chosen approach can provide additional insight into their function. Impact statement Using a whole network-based approach, our study characterizes the normal patterns (including resting-state activity [RSA], short- and long-range functional connectivity [FC]) of three prominent resting-state networks (rsNW) within the context of age-dependent changes and explores their relevance for different cognitive domains. Our results revealed a pattern with low RSA and FC in the salience network in healthy volunteers, whereas higher RSA, particularly in the central executive network, seemed to have a negative effect on cognition. These results increase the knowledge about the three core rsNWs and the understanding about their relevance for cognition.

S0501 Is Endoflip Useful and Reproducible for Assessment of Anorectal Sensation in Healthy Subjects?

INTRODUCTION: Abnormal anorectal sensation is commonly associated with anorectal disorders. Endoflip® is a novel technology that can measure anal canal sensation and distensibility. Aim: To determine anorectal sensory properties in healthy subjects using Endoflip and examine its reproducibility and validity. METHODS: Healthy subjects completed two studies of anal Endoflip, two weeks apart. An EndoFLIP probe (3-mm diameter, 8-cm long, highly compliant bag with 16 impedance sensors) was placed in the anus with center of balloon located in mid anal canal. Stool sensations (1 = no, 2 = First, 3 = Constant, 4 = Desire, 5 = Urgency to defecate) and discomfort/pain sensation (Likert 0-4) were assessed at each distending volume 10, 20, 30, 40, and 50 ml. Ramp and intermittent balloon distensions were performed in random sequence and during rest and squeeze. Test re-test reliability were assessed using intra-class correlation coefficient (ICC). RESULTS: Twelve healthy subjects (M/F = 5/7, 28.2 ± 9.5 years) participated. Mean scores for stool-like sensation increased stepwise, with both ramp and intermittent distensions, during rest and squeeze (Tables 1 and 2). Mean scores for discomfort/pain increased slightly and were below 0.8 (Table 1). For ramp distention, stool sensation during test showed high reproducibility for 10, 30, and 50 ml (ICC >0.686, P < 0.03, Table 1), and during squeeze for all balloon distension volumes (Table 1). For intermittent distention, the stool sensation at rest and with 10 ml and 20 mL were significantly reproducible, as well as for all distensions during squeeze manuever, and these were also highly reproducible (ICC > 0.681, P < 0.035, Table 2). Discomfort/pain during rest and squeeze for most balloon volumes high reproducibility (ICC > 0.764, P < 0.013, Tables 1 and 2). CONCLUSION: Endoflip is a reliable, noninvasive and useful tool for assessing anorectal stool sensation and discomfort. Data from ramp and intermittent methods were similar. It is potentially useful for assessment of anorectal sensation in anorectal disorders.Table 1Table 2

Association between human gray matter metabotropic glutamate receptor-5 availability in vivo and white matter properties: a [11C]ABP688 PET and diffusion tensor imaging study.

Excitatory corticofugal projections in the subcortical white matter (WM) convey signals arising from local neuronal activity in the gray matter (GM). We hypothesized that metabotropic glutamate receptor-5 (mGluR5) availability in GM, as a surrogate marker for local glutamatergic neuronal activity, correlates with WM properties in healthy brain. We examined the relationship in healthy individuals between GM mGluR5 availability measured in vivo using [11C]ABP688 positron emission tomography (PET) and WM properties measuredas fractional anisotropy (FA) using diffusion tensor imaging (DTI). Twenty-three healthy volunteers underwent this multimodal imaging. We calculated mGluR5 availability, [11C]ABP688 binding potential (BPND), using the simplified reference tissue model, and generated DTI FA maps using FMRIB's Diffusion Toolbox (FDT) along with Tract-Based Spatial Statistics (TBSS). To investigate the relationship between mGluR5 availability and FA, we performed voxel-wise and region of interest (ROI)-based analyses. The voxel-wise analysis showed significant positive correlations between the whole cerebral GM [11C]ABP688 BPND and the FA in widespread WM regions including the corpus callosum body, internal capsule, and corona radiata (FWE corrected p < 0.05). The ROI-based analysis also revealed significant positive correlations (Bonferroni-corrected threshold p < 0.00021) between [11C]ABP688 BPND in the frontal and parietal cortical GM and FA in the internal capsule (anterior limb and retrolenticular part). Using a novel multimodal imaging interrogation, we provide the first evidence that GM mGluR5 availability is significantly positively associated with WM properties in healthy subjects. Future comparison studies could determine whether this relationship is perturbed in neuropsychiatric disorders with dysregulated mGluR5 signaling.

EVALUATING CAROTID ARTERY DYNAMICS USING PRESSURE/DIAMETER WAVEFORMS TO DETERMINE STIFFNESS AND VISCOELASTIC PROPERTIES

Objective: Carotid stiffness as local Pulse Wave Velocity (cPWV), obtained by ultrasound during a scan, predicts risk of stroke and cognitive dysfunction independently of ambient blood pressure and age but remains pressure-dependent, complicating comparison between clinical groups. Our aim was to carry out multi-parametric analysis of carotid wall properties in healthy subjects and patients with different risk factors, compensating for the pressure-dependency of PWV. Design and method: Pressure (P) (PulsePen, DiaTecne, Milan, Italy, 500 or 1000 samples/s) and Diameter (D) (Aloka, Hitachi Ltd., Japan, 1000 samples/s, and MyLabOne, Esaote SpA, Italy, 660 samples/s) waveforms were acquired for the right and left common carotid artery of 210 subjects (117 men) at hospitals in Pisa and Massa (Tuscany, Italy). We included 81 age-matched healthy controls and patients treated for hypertension only (N = 28), hypertension with metabolic disorders (N = 31), dyslipidemia (mainly, hypercholesterolemia, N = 37), younger T1 diabetes (N = 19), and T2 diabetes (N = 14). The PD2-loop method was used to estimate cPWV, and the PD2 relationship was fitted with an exponential function P(t) = DBP*exp[γ(D(t)2/D_DBP2-1)]. The P-independent stiffness parameter γ was used for pressure normalization of cPWV to characterize the elastic component of arterial wall mechanical behaviour, as was the hysteresis area, defined as that within the plot of the PD-loop, for the viscous component.Results: In healthy subjects, cPWV increased with age from 4 m/s < 30 years to >=6 m/s in the eldest group. After pressure normalization to 110–75 mmHg, cPWV's increasing trend with age was still observed (Anova, p < 0.001) but total variation was reduced by 15% (left figure). Hypertensives and patients with metabolic disorders had higher cPWV than age-matched controls after pressure normalization and adjustment for age and heart rate. PD-loop hysteresis area was much greater in hypertension across the age range (right figure, p < 0.001). Conclusions: Overall, quantifying carotid wall viscosity through PD-loop assessment, in addition to pressure independent stiffness parameters, results in a promising tool to identify local mechanical pathology in hypertension and metabolic conditions.

Quantitative phase contrast MRI of penetrating arteries in centrum semiovale at 7T

Pathological changes of penetrating arteries (PA) within the centrum semiovale is an important contributing factor of cerebral small vessel disease (SVD). However, quantitative characterization of the PAs remains challenging due to their sub-voxel sizes. Here, we proposed a Model-based Analysis of Complex Difference images (MACD) of phase contrast MRI capable of measuring the mean velocities (vmean), diameters (D), and volume flow rates (VFR) of PAs without contamination from neighboring static tissues at 7 T.Simulation, phantom and in vivo studies were performed to evaluate the reproducibility and errors of the proposed method. For comparison, a Model-based Analysis of Phase difference images (MAP) was also carried out in the simulation. The proposed MACD analysis approach was applied in vivo to study the age dependence of PA properties in healthy subjects between 21 and 55 years old.Simulation showed that our proposed MACD approach yielded smaller errors than MAP, with errors increasing at lower velocities and diameters for both methods. In the phantom study, errors of the MACD-derived vmean, D, and VFR were ≤20% of their true values when vmean≥1cm/s and similar at different spatial resolutions. On the other hand, errors of the uncorrected apparent velocities were 24–60% and depended strongly on voxel size. The MACD errors linearly increased with the angle (α) between the vessel and slice normal direction at α ≤ 2° but remained almost constant at larger α. Results of the in vivo studies showed that the coefficients of repeatability for vmean, D, and VFR for PAs with α = 0° were 0.67 cm/s, 0.060 mm, and 0.067 mm3/s, respectively. No significant age dependence was found for the number, vmean, D, and VFR of PAs. The mean vmean, D, and VFR over all PAs with α = 0° were 1.79 ± 0.62 cm/s, 0.17 ± 0.05 mm, and 0.36 ± 0.18 mm3/s, respectively.Quantitative measurements of PAs with the MACD method may serve as a useful tool for illuminating the vascular pathology in cerebral SVD.

Correlations between three-dimensional speckle-tracking echocardiography-derived left atrial functional parameters and aortic stiffness in healthy subjects - Results from the MAGYAR-Healthy Study.

Left atrial (LA) distension has been demonstrated to be linked with aortic stiffness in different patient populations. Three-dimensional (3D) speckle-tracking echocardiography (STE) seems to be a promising tool for volumetric and functional evaluation of the LA. The aim of the present study was to determine whether correlations exist between 3DSTE-derived LA volume-based and strain parameters characterizing all phasic functions of the LA and echocardiographic aortic elastic properties in healthy subjects. The study included 19 healthy volunteers (mean age: 37.9 ± 11.4 years, 11 men) who had undergone complete two-dimensional (2D) Doppler transthoracic echocardiography extended with the assessment of aortic elastic properties and 3DSTE. None of LA volumes correlated with echocardiographic aortic elastic properties. Active atrial stroke volume correlated with aortic stiffness index (ASI, r = 0.45, p = 0.05). None of other volume-based functional properties significantly correlated with aortic stiffness parameters. Global peak 3D strain correlated with aortic strain (r = ‒0.46, p = 0.05). global radial pre-atrial contraction strain correlated with ASI (r = ‒0.49, p = 0.04) and AS (r = ‒0.50, p = 0.04). Correlations exist between 3DSTE-derived LA functional parameters and eschocardiographic aortic elastic properties in healthy subjects.

Comparison of Three‐Dimensional Speckle Tracking Echocardiography and Two‐Dimensional Echocardiography for Evaluation of Left Atrial Size and Function in Healthy Volunteers (Results from the MAGYAR‐Healthy Study)

Noninvasive accurate assessment of left atrial (LA) size and function is an essential requirement in daily clinical practice. Real time three-dimensional (3D) echocardiography (RT3DE) with direct volumetric method has been found to be a highly accurate and reproducible noninvasive tool for the evaluation of LA dimensions and functional properties. Three-dimensional speckle tracking echocardiography (3DSTE) has just been introduced for volumetric assessments, which uses different, as called "block-matching" algorithm by strain analysis. This study was designed to compare two-dimensional (2D) echocardiography with 3DSTE for calculation of LA volumes and assessment of LA functional properties in healthy subjects. This study comprised of randomly selected 35 healthy subjects (40.9 ± 10.9 years, 20 men) in sinus rhythm, they all had undergone standard transthoracic 2D echocardiographic Doppler study extended with 3DSTE. Two-dimensional echocardiography- and 3DSTE-derived minimum (Vmin ) and maximum (Vmax ) LA volumes and LA volume before atrial contraction (Vpre A ) did not differ significantly. Calculated functional LA properties were also compared. Good correlations were found between both techniques for Vmax (r = 0.93, P < 0.0001), Vmin (r = 0.62, P < 0.0001), and Vpre A (r = 0.74, P < 0.0001). It may be stated that 3DSTE seems to be feasible in detection of cyclic changes in LA volumes and calculation of its functional properties is comparable to 2D echocardiography.

Effects of hyperoxia on the relationship between heart rate variability, blood pressure and arterial wall properties in healthy subjects

Effects of hyperoxia on the relationship between heart rate variability, blood pressure and arterial wall properties in healthy subjects

To assess the difference in the corneal biomechanical properties in healthy subjects with and without their contact lenses

AbstractPurpose To assess the difference in the corneal biomechanical properties in healthy subjects with and without their contact lenses.Methods The study included one eye of 20 healthy subjects who wear monthly, soft contact lenses for a refractive error. The subjects were asked, not to wear their contact lenses during at least 12 hours. The central corneal thickness was measured at least 30 minutes before other examination using an ultrasonic pachymeter. The corneal biomechanical properties and the intraocular pressure (IOP) were measured by ocular response analyzer (ORA). The measurements were repeated immediately with the contact lenses. A student t‐test was used to assess the difference between the measurements with and without contact lenses.Results The mean corneal hysteresis without and with contact lenses were 10.88 ± 1.8 mmHg (9.6‐13.7 mmHg) and 10.92 ± 1.7 mmHg (8.5‐13.4 mmHg), respectively (p = 0.16). The mean corneal resistance factor was 9.96 ± 1.7 mmHg (7.9‐12.6 mmHg) without contact lenses compared with 9.95 ± 2.1 mmHg (7.6‐12.3 mmHg) with the contact lenses (p= 0.21) There was no significant difference nor in corneal‐compensated IOP neither in Goldmann‐correlated IOP, with or without the contact lenses.Conclusion Our results suggest that ORA‐generated parameters are not influenced by the contact lens itself. Further longitudinal studies should be performed to establish the eventual changes of the biomechanical parameters with duration of the contact lens wear.

A mechanism‐based model for the population pharmacokinetics of free and bound aflibercept in healthy subjects

Aflibercept (VEGF-Trap), a novel anti-angiogenic agent that binds to VEGF, has been investigated for the treatment of cancer. The aim of this study was to develop a mechanism-based pharmacokinetic (PK) model for aflibercept to characterize its binding to VEGF and its PK properties in healthy subjects. Data from two phase I clinical studies with aflibercept administered as a single intravenous infusion were included in the analysis. Free and bound aflibercept concentration-time data were analysed using a nonlinear mixed-effects modelling approach with MONOLIX 3.1. The best structural model involved two compartments for free aflibercept and one for bound aflibercept, with a Michaelis-Menten type binding of free aflibercept to VEGF from the peripheral compartment. The typical estimated clearances for free and bound aflibercept were 0.88 l day(-1) and 0.14 l day(-1), respectively. The central volume of distribution of free aflibercept was 4.94 l. The maximum binding capacity was 0.99 mg day(-1) and the concentration of aflibercept corresponding to half of maximum binding capacity was 2.91 µg ml(-1). Interindividual variability of model parameters was moderate, ranging from 13.6% (V(max) ) to 49.8% (Q). The present PK model for aflibercept adequately characterizes the underlying mechanism of disposition of aflibercept and its nonlinear binding to VEGF.

Biomechanical properties in healthy subjects with and without refractive errors. A comparative study

Abstract Purpose To determine in vivo corneal biomechanical properties in patients without refractive errors and patients with moderate‐high myopic and hyperopic spherical refractive errors. Methods A comparative study was carried out to measure Corneal Hysteresis (CH, mmHg) and Corneal Resistance Factor (CRF, mmHg) of 384 eyes of 201 patients classified in four groups. Moderate myopia (&lt; 6 D, n=203), high myopia (&gt; 6 D, n=43), moderate‐high hyperopia (&gt; 2 D, n=62), and emetropic group (n=76). Corneal compensated intraocular pressure (IOPcc),and Goldman correlated intraocular pressure (IOPg) were also studied. Central corneal thickness (CCT, microns) was measured by ultrasonic pachymetry. Patients with ocular pathology or astigmatism greater than the spherical refractive error were not considered. A multiple‐comparison analysis was made to establish differences among the groups. Results Mean values were: CH= 10.59±1.52, CRF= 10.52±1.69 and CCT= 556.3 for the moderate myopia group, CH=10.04 ±1.55, CRF=10.23 ±1.82 and CCT=543.75 for the high myopia group, CH=11.16 ±1.88, CRF=10.69 ±2.07 and CCT=555.43 for the hyperopia group, CH=10.66 ±1.30 , CRF=10.48±1.14 and CCT=558.10 for the control group. Although these results of the biomechanical parameters showed higher values corresponding to the hyperopia group and lower to the myopia group, these differences were not statistically significant. Conclusion CH and CRF are greater in hyperopic patients in comparison with myopic and emetropic eyes. We do not find statistical significant differences between moderate myopia and high myopia. There are significant differences in CH between the high myopia and the hyperopia groups.

Characterization of vascular reactivity in dorsal hand veins after oral rosiglitazone treatment in healthy subjects

In clinical studies with diabetic patients thiazolidinediones have been shown to restore abnormal vascular function which might be attributed to improved blood sugar control or to restoration of vascular endothelium and smooth muscle responsiveness. The present study was undertaken to investigate whether rosiglitazone modulates vascular responsiveness to different vasoactive agents and exerts renin-angiotensin-system (RAS)-inhibiting properties in healthy subjects in vivo. 24 healthy male subjects were randomized to receive either rosiglitazone or placebo. Venoconstrictor responses to angiotensin II (Ang II) and phenylephrine, and endothelium-dependent response to histamine and insulin, and endothelium-independent response to glyceroltrinitrate were compared using the dorsal hand vein compliance method. Effects on the RAS were investigated by plasma level determinations of Ang II and angiotensin-(1-7). Treatment effects on the systemic arterial system were investigated by standardized pulse-wave-analysis. Rosiglitazone significantly inhibited venoconstrictor responses to Ang II by 19% (-70% vs. -51% constriction, p = 0.034) and in the presence of rosiglitazone the ED80 for phenylephrine was increased (ED80: 317 A+/- 86 ng vs. 531 A+/- 102 ng; p = 0.010). Rosiglitazone treatment was without effect on endothelium-dependent dilation, blood pressure, pulse-wave-velocity and plasma angiotensin peptide levels. The data of the present study in veins of healthy subjects are consistent with data from in vitro and animal studies supporting a direct effect of rosiglitazone on venous tone by modulation of the vascular smooth muscle response via AT1-receptor-downregulation.

Exercise-induced Sweating in Healthy Subjects as a Model to Predict a Drug’s Sweat-reducing Properties in Hyperhydrosis: a Prospective, Placebo-controlled, Double-blind Study

The aim of this study was to develop a model to evaluate the efficacy of drugs with expected sweat-reducing properties in healthy subjects in order to select candidate drugs for the systemic treatment of primary generalized hyperhidrosis. A randomized, double-blind, placebo-controlled cross-over study was performed in 8 healthy subjects. Sweating was induced by exercise. The degree of sweating at different exercise levels was determined by measurement of transepidermal water loss. Either the anticholinergic drug oxybutynin or placebo was given before measurements started. No statistically significant differences in transepidermal water loss between active treatment and placebo were found at the different exercise levels. This is noteworthy, as oxybutynin has been proven successful in patients with generalized hyperhidrosis. Thus, the present model does not mimic the situation in patients with primary generalized hyperhidrosis. This may be because this form of hyperhidrosis is not caused only by sympathetic overactivity, as described in the literature, but is based on more complex mechanisms. Further investigations are required fully to understand the pathophysiology of primary generalized hyperhidrosis in order to develop effective human test models.

Effect of Limb Immobilization on Venous Properties in Healthy Subjects

Effect of Limb Immobilization on Venous Properties in Healthy Subjects

Exercise and the inflammatory response in chronic obstructive pulmonary disease (COPD)—Does training confer anti-inflammatory properties in COPD?

There is increasing evidence that systemic inflammation plays an important role in the pathogenesis of COPD. Inflammatory markers show relationships with exercise performance, health related quality of life and breathlessness. These are important clinical outcomes in the management of COPD. Even more so is the consideration that systemic inflammation in COPD may be directly associated with mortality and deterioration of disease. Long-term exercise training clearly has beneficial properties in healthy subjects, whether the same is true in COPD remains to be seen. This review discusses aspects of the anti-inflammatory effects of exercise in relation to patients with COPD. There is intriguing evidence that the exercise-induced cytokine response differs in COPD patients compared with healthy subjects. We consider the role of IL-6 in the manifestation of fatigue in COPD and consider the implications of raised CRP- and TNF-alpha. Early data suggests beneficial effects of polyunsaturated fatty acid PUFA supplementation and exercise training in combination with appropriate nutritional support may yield rewarding therapeutic benefits. This review raises the hypothesis that physical training in COPD is associated with immunological changes that may confer anti-inflammatory benefits and in part, explain changes seen after pulmonary rehabilitation in COPD patients.

Probiotics and immune response.

For many years, probiotic bacteria have been known to confer health benefits to the consumer. In 1989, probiotics were defined as “a live microbial feed supplement which beneficially effects the host animal by improving its intestinal microbial balance” (1). To date, this definition can be extended, as recent developments claim a role for probiotics and their active cellular substances in the intestinal and extraintestinal physiology of the host. Lactic-acid bacteria (LAB), including lactobacilli and bifidobacteria, were shown to prevent adherence, establishment, and replication of several enteropathogens through antimicrobial mechanisms (2–4) and modulation of the host mucosal immune response. LAB were also reported to inhibit growth of H. pylori in vitro (5) and L.johnsonii La1 demonstrated a long-term suppressive effect on H. pylori in humans (6). Finally, the preventive and therapeutic effect of several LAB on gastrointestinal disorders (7,8) and diarrhea caused by rotavirus has been established in several human intervention studies (9,10). Among the various lactobacilli, some strains also show immunostimulatory properties in healthy subjects by enhancing innate immune mechanisms. Schiffrin et al. showed an increase in phagocytosis of peripheral-blood mononuclear cells (PBMCs) after consumption of L. johnsonii La1 (11). Moreover, fermented milk products, containing L. johnsonii La1 and B. bifidum had immune adjuvant effects (significant increase in total and specific serum IgA) when administered in conjunction with an attenuated oral Salmonella typhi vaccine (12). Immuno-