Lactobacillus johnsonii La1 attenuates Helicobacter pylori-associated gastritis and reduces levels of proinflammatory chemokines in C57BL/6 mice

In clinical settings, Lactobacillus johnsonii La1 administration has been reported to have a favorable effect on Helicobacter pylori-associated gastritis, although the mechanism remains unclear. We administered, continuously through the water supply, live La1 to H. pylori-infected C57BL/6 mice and followed colonization, the development of H. pylori-associated gastritis in the lamina propria, and the levels of proinflammatory chemokines macrophage inflammatory protein 2 (MIP-2) and keratinocyte-derived cytokine (KC) in the serum and gastric tissue over a period of 3 months. We documented a significant attenuation in both lymphocytic (P=0.038) and neutrophilic (P=0.003) inflammatory infiltration in the lamina propria as well as in the circulating levels of anti-H. pylori immunoglobulin G antibodies (P=0.003), although we did not observe a suppressive effect of La1 on H. pylori colonizing numbers. Other lactobacilli, such as L. amylovorus DCE 471 and L. acidophilus IBB 801, did not attenuate H. pylori-associated gastritis to the same extent. MIP-2 serum levels were distinctly reduced during the early stages of H. pylori infection in the La1-treated animals, as were gastric mucosal levels of MIP-2 and KC. Finally, we also observed a significant reduction (P=0.046) in H. pylori-induced interleukin-8 secretion by human adenocarcinoma AGS cells in vitro in the presence of neutralized (pH 6.8) La1 spent culture supernatants, without concomitant loss of H. pylori viability. These observations suggest that during the early infection stages, administration of La1 can attenuate H. pylori-induced gastritis in vivo, possibly by reducing proinflammatory chemotactic signals responsible for the recruitment of lymphocytes and neutrophils in the lamina propria.     

Relationship between pulse amplitude and thermal exchange in the finger: the effect of smoking

In 24 healthy volunteers finger pulse amplitude and heart rate (HR) were monitored by pulse plethysmography and thermal exchange from the finger and were compared before and after the smoking of a single cigarette. Thermal exchange was measured using a direct calorimeter consisting of a recording bath and a reference bath, both of which were filled with water at 18 degree C. The subject immersed the two distal phalanx of a finger into the recording bath. The water thermal gradient between both baths after 4 min of finger immersion and the maximal value of heat loss from the finger to the water were recorded. Decreases in the water thermal gradient (from 6.06 to 5.33 degrees C, P less than 0.05) in maximal value of heat loss (from 22.5 to 18.75 w.m-2, P less than 0.01) and in plethysmographic wave amplitude (from 25.8 to 14.6 mm, P less than 0.01) and increased HR (from 72 to 83 beats min-1) were observed in smokers. These changes were not statistically significant in non-smokers. Water thermal gradient and maximal value of heat loss correlated with plethysmographic wave amplitude before and after smoking but not with HR in the 24 subjects studied. The present study shows a good relationship between vascular phenomena and thermal exchange in the fingers. The variations of finger pulse amplitude provide an adequate and sensitive adjustment of thermal exchange since the effects of smoking a single cigarette can be detected by both PWA and calorimetric measurements in the finger.     

Short-arm (1.9 m) +2.2 Gz acceleration: isotonic exercise load-O2 uptake relationship

BACKGROUND: The deconditioning syndrome from prolonged bed rest (BR) or spaceflight includes decreases in maximal oxygen uptake (VO2max), muscular strength and endurance, and orthostatic tolerance. In addition to exercise training as a countermeasure, +Gz (head-to-foot) acceleration training on 1.8-2.0 m centrifuges can ameliorate the orthostatic and acceleration intolerances induced by BR and immersion deconditioning. PURPOSE: Study A was designed to determine the magnitude and linearity of the heart rate (HR) response to human-powered centrifuge (HPC) acceleration with supine exercise vs. passive (no exercise) acceleration. Study B was designed to test the hypothesis that moderate +Gz acceleration during exercise will not affect the respective normal linear relationships between exercise load and VO2max, HR, and pulmonary ventilation (VEBTPS). Study C: To determine if these physiological responses from the HPC runs (exercise + on-platform acceleration) will be similar to those from the exercise + off-platform acceleration responses. METHODS: In Study A, four men and two women (31-62 yr) were tested supine during exercise + acceleration and only passive acceleration at 100% [maximal acceleration (rpm) = Amax] and at 25%, 50%, and 75% of Amax. In Studies B and C, seven men (33+/-SD 7 yr) exercised supine on the HPC that has two opposing on-platform exercise stations. A VO2max test and submaximal exercise runs occurred under three conditions: (EX) exercise (on-platform cycle at 42%, 61%, 89% and 100% VO2max) with no acceleration; (HPC) exercise + acceleration via the chain drive at 25%,50%, and 100% Gzmax (35%, 72% and 100% VO2max); and (EXA) exercise (on-platform cycle at 42%, 61%, 89%, and 100% VO2max) with acceleration performed via the off-platform cycle operator at +2.2+/-0.2 Gz [50% of max (rpm) G]. RESULTS: Study A: Mean (+/-SE) Amax was 43.7+/-1.3 rpm (mean = +3.9+/-0.2, range = 3.3 to 4.9 Gz). Amax run time for exercise +acceleration was 50-70 s, and 40-70 s for passive acceleration. Regression of X HR on Gz levels indicated explained variances (r2) of 0.88 (exercise) and 0.96 (passive). The mean exercise HR of 107+/-4 (25%), to 189+/-13 (100%) bpm were 43-50 bpm higher (p < 0.05) than comparable passive HR of 64+/-2 to 142+/-22 bpm, respectively. Study B: There were no significant differences in VO2, HR or VEBTPS at the submaximal or maximal levels between the EX and EXA runs. Mean (+/-SE) VO2max for EX was 2.86+/-0.12 L x min(-1)(35+/-2 ml x min(-1) x kg(-1)) and for EXA was 3.09+/-0.14 L x min(-1) (37+/-2 ml-min(-1) x kg(-1)). Study C: There were no significant differences in the essentially linear relationships between the HPC and EXA data for VO2 (p = 0.45), HR (p < 0.08), VEBTPS (p = 0.28), or the RE (p = 0.15) when the exercise load was % VO2max. CONCLUSION: Addition of + 2.2 Gz acceleration does not significantly influence levels of oxygen uptake, heart rate, or pulmonary ventilation during submaximal or maximal cycle ergometer leg exercise on a short-arm centrifuge.     

Human kallikrein 6 (hK6): a new potential serum biomarker for diagnosis and prognosis of ovarian carcinoma.

PURPOSE: The discovery of new ovarian cancer biomarkers that are suitable for early disease diagnosis and prognosis may ultimately lead to improved patient management and outcomes. PATIENTS AND METHODS: We measured, by immunoassay, human kallikrein 6 (hK6) concentration in serum of 97 apparently healthy women, 141 women with benign abdominal diseases, and 146 women with histologically proven primary ovarian carcinoma. We then calculated the diagnostic sensitivity and specificity of this test and examined the association of serum hK6 concentration with various clinicopathologic variables and patient survival. RESULTS: Serum hK6 concentration between normal and benign disease patients was not different (mean, 2.9 and 3.1 micro g/L, respectively). However, hK6 in presurgical serum of ovarian cancer patients was highly elevated (mean, 6.8 micro g/L; P <.001). Serum hK6 decreased after surgery (to a mean of 3.9 micro g/L) in 68% of patients. The diagnostic sensitivity of serum hK6 at 90% and 95% specificity is 52% and 47%, respectively, in the whole patient population. For early stage disease (stage I or II), sensitivity is approximately 21% to 26%. When combined with CA-125, at 90% specificity, sensitivity increases to 72% (for all patients) and to 42% in stage I or II disease. Serum hK6 concentration correlates moderately with CA-125 and is higher in patients with late-stage, higher-grade disease and in patients with serous histotype. Preoperative serum hK6 concentration is a powerful predictor of disease-free and overall survival in both univariate and multivariate analyses. CONCLUSIONS: Serum hK6 concentration seems to be a new biomarker for ovarian carcinoma and may have value for disease diagnosis and prognosis.     

Downregulation of human kallikrein 10 (KLK10/NES1) by CpG island hypermethylation in breast, ovarian and prostate cancers.

OBJECTIVE: The human kallikrein 10 (KLK10)/normal epithelial cell-specific-1 (NES1) gene is highly expressed in normal mammary, ovary and prostate cells, but its expression is dramatically decreased in cancer cell lines. Recently, it has been shown that CpG island hypermethylation of the KLK10 gene is responsible for the tumor-specific loss of KLK10 gene expression in certain breast cancer cell lines. METHOD: We examined the role of CpG island hypermethylation in the tumor-specific loss of KLK10 expression in breast, ovarian and prostate cancers. We treated cells with the demethylating agent 5-aza-2'-deoxycytidine (dC) and monitored changes in KLK10 mRNA by RT-PCR and secreted hK10 protein expression by ELISA. The following cell lines were used: MDA-MB-231, MDA-MB-468, MCF-7, ZR-75-1, T-47D and BT-474 (breast); BG-1, MDAH-2774, HTB-75, HTB-161, PA-1 and ES-2 (ovary), and LNCaP and PC-3 (prostate). RESULTS: Upregulation of KLK10 mRNA levels, which was accompanied by an increase in secreted hK10 protein concentration, was observed for a subset of breast, ovarian, and prostate tumor cell lines after 5-aza-2'-dC. Genomic sequencing of sodium-bisulfite-treated DNA demonstrated that CpG sites within the KLK10 gene exon 3 were highly methylated. Hypermethylation of exon 3 CpG regions was also detected in primary ovarian cancers. CONCLUSION: These data suggest that CpG island hypermethylation plays an important role in the downregulation of kallikrein 10 mRNA and protein expression, but it cannot explain the pattern of expression of this gene in all cell lines or tissue tested.     

Carotid–Femoral Pulse Wave Velocity Assessed by Ultrasound: A Study with Echotracking Technology

Described here is a new method for determination of carotid–femoral pulse wave velocity (PWV) based on arterial diameter waveform recording by an ultrasound system. The study was carried out on 120 consecutive patients. Carotid–femoral PWV was determined using a tonometric technique (PWVpp, PulsePen, DiaTecne, Milan, Italy) and an echotracking ultrasound system (PWVet, E-Track, Aloka, Tokyo, Japan). The relationship between PWVpp and PWVet was evaluated by linear regression and Bland–Altman analysis. There was excellent agreement between PWVet and PWVpp (Pearson's r = 0.94, 95% confidence interval: 0.91–0.96, p < 0.0001; PWVet = 0.88 × PWVpp + 0.57). The Bland–Altman plot revealed an offset of ?0.33 m/s with limits of agreement from ?2.21 to 1.54 m/s. The coefficients of variation for within-subject repeatability between PWVet and PWVpp had were 5.79% and 8.47%, respectively, without significant differences in the Bland–Altman analysis. The results suggest that echotracking technology can provide a reliable estimate of aortic stiffness comparable to that of the tonometric techniques.     

Coronary and peripheral blood flow changes following biventricular pacing and their relation to heart failure improvement.

AIMS: To study the effect of cardiac resynchronization therapy (CRT) on coronary and peripheral arterial circulation and to assess whether their changes are related to the improvement in patients' functional capacity and prognostically important biochemical markers. METHODS AND RESULTS: Twenty-five patients were studied (New York Heart Association classes III and IV, left ventricular ejection fraction <35%, QRS>120 ms, mean age 66 +/- 2.1 years). Coronary blood flow (CBF), forearm blood flow (FBF), and their reserve were measured by transoesophageal echocardiography (in cm/s) and venous occlusion plethysmography (in mL/100 mL/min) at baseline and following 3 months of CRT. N-terminal-pro-brain natriuretic peptide (Nt-pro-BNP) and serum adhesion molecules, sICAM-1 and sVCAM-1 levels were also assessed. CRT induced a non-significant increase in resting CBF (baseline vs. CRT: 52.1 +/- 5.5 vs. 58.2 +/- 3.6, P: NS), whereas hyperaemic CBF was increased by CRT (baseline vs. CRT: 67.8 +/- 6.8 vs. 79.8 +/- 6.2, P < 0.05). Significant increases were observed in resting FBF (baseline vs. CRT: 1.6 +/- 0.2 vs. 2.6 +/- 0.2, P < 0.05) and hyperaemic FBF (baseline vs. CRT: 2.1 +/- 0.2 vs. 3.2 +/- 0.3, P < 0.05). The per cent difference in hyperaemic FBF was related to the per cent change in Nt-pro-BNP (r = -0.71, P < 0.05) and the per cent improvement in exercise duration (r = 0.80, P < 0.05). CONCLUSION: CRT induces favourable changes in coronary and peripheral arterial function. Changes in peripheral blood flow are related to patients' improvement and may be prognostically significant.