Azithromycin does not prevent six-month myointimal proliferation but attenuates the transient systemic inflammation occurring after coronary stenting

Stent implantation produces a systemic increase of inflammatory markers that correlates with Chlamydophila pneumoniae infection in atherosclerotic plaque. We performed a clinical intervention study to investigate the effect of antibiotic treatment on 6-month follow-up angiographic minimal luminal diameter after stenting. Ninety patients were randomly assigned to oral azithromycin or placebo in a double-blinded and randomized fashion. Medication was initiated 2 weeks before a pre-scheduled stenting procedure and maintained 12 weeks thereafter. Angiographic outcomes were evaluated by a six-month follow-up angiography and laboratorial parameters were accessed by blood sampling 2 weeks before stenting, within the first 24 h after procedure and additional samples after four weeks and 6 months. Minimal luminal diameter (1.76 +/- A 0.56 mm Vs. 1.70 +/- A 0.86 mm; P = 0.7), restenosis rate, diameter stenosis, late loss, and binary restenosis rates were comparable in placebo and azithromycin group in the 6 months follow-up. Serum levels of C-reactive protein presented a three fold significant increase in the control group one day after stenting but did not change in the azithromycin group (8.5 [3.0;16.4] Vs. 2.9 [1.7;6.6]-median [25;75 percentile] P < 0.01). Azithromycin does not improve late angiographic outcomes but attenuates the elevation of C-reactive protein levels after stenting, indicating an anti-inflammatory effect.

Absence of galectin-3 does not affect the development of experimental tongue carcinomas in mice

Background: Galectin-3 is a lectin that presents pivotal roles in tumor biology and there are no studies evaluating their expression in dysplasias and carcinomas developed from tongue carcinogenesis models. Aims: To investigate the role of galectin-3 in the development of tongue carcinomas using a mouse model of oral carcinogenesis. Methods: Galectin-3-deficient (gal3(-/-)) and wild-type (gal3(+/+)) mice were challenged with 4-nitroquinoline-1-oxide in drinking water for 16 weeks and killed at different times. Tongues were removed and the number of dysplasias and carcinomas was counted. An immunohistochemical study for galectin-3 was performed only in the tongue from gal3(+/+) mice. Results: In both groups, a reduction of dysplasias and an increase of carcinomas from week 16 to week 32 (p > 0.05) were observed. A predominance of high cytoplasmic and nuclear galectin-3 expression was observed in carcinomas (64.7%) and dysplasias (55.5%), respectively (p > 0.05). The perilesional areas always presented a statistical cytoplasmic and nuclear galectin-3 overexpression. Conclusions: Absence of galectin-3 did not directly affect the process of carcinogenesis and a cytoplasm shift of galectin-3 seems to be associated with development of tongue carcinomas. (C) 2010 Elsevier Inc. All rights reserved.

Activation of the Wnt/Beta-catenin Signaling Pathway during Oral Carcinogenesis Process Is Not Influenced by the Absence of Galectin-3 in Mice

Background/Aim: Galectin-3 has been associated with activated Wnt pathway, translocating beta-catenin into the nucleus. However, it is still unknown whether this lectin drives the Wnt signaling activation in lesions from galectin-3-deficient (Gal3(-/-)) mice. The purpose was to study beta-catenin expression in tongue lesions from Gal3(-/-) and wildtype (Gal3(+/+)) mice and the status of Wnt signaling. Materials and Methods: Twenty Gal3(-/-) and Gal3(+/+) male mice were challenged with 4-nitroquinolin-1-oxide and killed at week 16 and 32. Tongues were processed and stained with H&E to detect dysplasias and carcinomas. An imunohistochemical assay was performed to evaluate beta-catenin expression. Results: Carcinomas were more evident in Gal3(+/+) than Gal3(-/-) mice (55.5% vs. 28.5%, respectively; p>0.05). Elevated expression of non-membranous beta-catenin was observed in dysplasias and carcinomas from both groups (p>0.05). Conclusion: Absence of galectin-3 does not interfere in the pattern of beta-catenin expression and therefore in the mediation of the Wnt signaling pathway.

Goal setting among adolescents: A comparison of delinquent, at risk, and not-at-risk youth

A series of studies was conducted to compare group differences in the goal orientations of delinquent, at-risk, and not-at-risk adolescents. An Importance of Goals Scale was developed by examining the item responses of 230 high school students and validated by administering the revised scale to 80 delinquent, 90 at-risk, and 90 not-at-risk adolescents. Results identified differences in the importance attributed to different goals by the 3 groups. Delinquent and at-risk adolescents attached significantly more importance to goals associated with developing a social image (e.g., delinquency, freedom-autonomy), whereas not-at-risk adolescents were more concerned with goals associated with an academic image (e.g., educational, interpersonal). Results are discussed in terms of their implications for school achievement, peer relations, and future life paths.

Oral cavity is not a reservoir for Helicobacter pylori in infected patients with functional dyspepsia

Helicobacter pylori infection is very prevalent in Brazil, infecting almost 65% of the population. The aim of this study was to evaluate the presence of this bacterium in the oral cavity of patients with functional dyspepsia (epigastric pain syndrome), establish the main sites of infection in the mouth, and assess the frequency of cagA and vacA genotypes of oral H. pylori. All 43 outpatients with epigastric pain syndrome, who entered the study, were submitted to upper gastrointestinal endoscopy to rule out organic diseases. Helicobacter pylori infection in the stomach was confirmed by a rapid urease test and urea breath tests. Samples of saliva, the tongue dorsum and supragingival dental plaque were collected from the oral cavity of each subject and subgingival dental plaque samples were collected from the patients with periodontitis; H. pylori infection was verified by polymerase chain reaction using primers that amplify the DNA sequence of a species-specific antigen present in all H. pylori strains; primers that amplify a region of urease gene, and primers for cagA and vacA (m1, m2, s1a, s1b, s2) genotyping. Thirty patients harbored H. pylori in the stomach, but it was not possible to detect H. pylori in any oral samples using P1/P2 and Urease A/B. The genotype cagA was also negative in all samples and vacA genotype could not be characterized (s-m-). The oral cavity may not be a reservoir for H. pylori in patients with epigastric pain syndrome, the bacterium being detected exclusively in the stomach.

Progesterone, estrogen and pregnancy do not decrease colon myoelectric activity in rats: An in vivo study

Background: Progesterone, estrogen and the hormonal complex of pregnancy have been responsible for some degree of colon hypomotility in human pregnancy. Objective: To find out if estrogen, progesterone and the hormonal complex of pregnancy decrease colon myoelectric activity. Methods: The study was performed in 37 healthy female rats in which electrodes were implanted on the serosa of the proximal ascendent, distal ascendent, transverse, and descendent colon. We analyzed the records of colon myoelectric activity in vivo in five groups: control, ovariectomized, ovariectomized and treated with estrogen, ovariectomized and treated with progesterone, and pregnant rats. Results: We found a great variation in myoelectric activity in all groups studied. The mean of electric activity did not show statistical difference among the five groups, but pregnant rats had a statistically significant higher duration of maximum electric activity in all distances from the cecocolon junction. Conclusion: Pregnant rats had a statistically higher duration of maximum electric activity. If we could transpose these results to humans, this increase in duration of colon myoelectric activity could explain, in part, the slight constipation that some pregnant women have. Copyright (C) 2008 S. Karger AG, Basel.

Inactivation of a c-Myb/estrogen receptor fusion protein in transformed primary cells leads to granulocyte/macrophage differentiation and down regulation of c-kit but not c-myc or cdc2

Primary murine fetal hemopoietic cells were transformed with a fusion protein consisting of the ligand-binding domain of the estrogen receptor and a carboxyl-terminally truncated c-Myb protein (ERMYB), The ERMYB-transformed hemopoietic cells exhibit an immature myeloid phenotype when grown in the presence of beta-estradiol. Upon removal of beta-estradiol, the ERMYB cells display increased adherence, decreased clonogenicity and differentiate to cells exhibiting granulocyte or macrophage morphology, The expression of the c-myc, c-kit, cdc2 and bcl-2 genes, which are putatively regulated by Myb, was investigated in ERMYB cells grown in the presence or absence of beta-estradiol. Neither c-myc nor cdc2 expression was down-regulated after removal of beta-estradiol demonstrating that differentiation is not a consequence of decreased transactivation of these genes by ERMYB. While bcl-2 expression was reduced by 50% in ERMYB cells grown in the absence of beta-estradiol, there was no increase in DNA laddering, suggesting that Myb was not protecting ERMYB cells from apoptosis, In contrast, a substantial (200-fold) decrease in c-kit mRNA level was observed following differentiation of ERMYB cells, and c-kit mRNA could be partially re-induced by the re-addition of beta-estradiol. Furthermore, a reporter construct containing the c-kit promoter was activated when cotransfected with a Myb expression vector, providing further evidence of a role for Myb in the regulation of c-kit.

Endometriosis of the ureter and bladder are not associated diseases

Objective: To verify whether bladder and ureter endometriosis had the same clinical features and disease behavior. Design: Case-control study. Setting: Multidisciplinary group in Sao Paulo, Brazil. Patient(s): A total of 690 patients were submitted to laparoscopy with histologically diagnosis of endometriosis between July 1999 and December 2006. Twelve of these patients had lesions affecting the ureter and 26 had lesions affecting the bladder. A control group consisted of 652 patients in whom endometriosis was not affecting either the ureter or the bladder. Intervention(s): None. Main Outcome Measure(s): Clinical and surgical features of patients with ureteral or bladder endometriosis. Result(s): No patients with ureteral endometriosis had lesions affecting the bladder. Compared with the control group, patients with ureteral endometriosis had more advanced disease (Stages III and IV) according to the American Society of Reproductive Medicine (ASRM) staging classification (100% vs. 65.5%); they also had more retrocervical (83.3% vs. 21.6%) and rectum-sigmoid lesions (91.7% vs. 17.9%). Compared with the control group, more patients with bladder endometriosis had cyclic dysuria and/or hematuria (34.6% vs. 9.8%), more advanced stages of the disease (88.4% vs. 65.5%), and an association with endometriosis of the rectum-sigmoid (65.3% vs. 17.9%). Conclusion(s): Ureter endometriosis is not associated with the bladder disease; however, it is associated with advanced ASRM stages and with retrocervical and rectum-sigmoid lesions. (Fertil Steril (R) 2009;91:1662-7. (C)2009 by American Society for Reproductive Medicine.)

Interleukin-12 but not interieukin-18 is associated with severe endometriosis

Objective: To evaluate interleukin (IL)-12 and IL-18 levels in the serum and peritoneal fluid of women with and without endometriosis. Design: Cross-sectional survey. Setting: University hospital. Patients: Interleukin-12 and IL-18 levels were compared in 105 patients submitted to laparoscopy because of symptoms suggestive of endometriosis (pain and/or infertility). The disease was confirmed in 72 patients (study group), while in 33 patients findings were not compatible with endometriosis (control group). Intevention(s): Blood sample and peritoneal fluid were obtained from patients during videolaparoscopy. Main Outcome Measure(s): The levels of IL-12 and IL-18 in peripheral blood and peritoneal fluid were determined and compared with the stage and site of the disease and histologic classification. Result(s): IL-12 levels measured in peritoneal fluid were higher inpatients with endometriosis compared with the control group. A significant increase in IL-12 levels was found when the more advanced stages of the disease were compared with the initial stages. No statistically significant differences were found in IL-18 levels, either in serum or in peritoneal fluid samples. Conclusion(s): Patients with severe endometriosis have higher IL-12 levels irrespective of IL-18 levels, suggesting that in this disease an alternative pathway is involved in induction of the Th1 immune response. (Fertil Steril (R) 2009;91:320-4. (C)2009 by American Society for Reproductive Medicine.)

POLYETHYLENE GLYCOL ADDITION DOES NOT IMPROVE EXOGENOUS SURFACTANT FUNCTION IN AN EXPERIMENTAL MODEL OF MECONIUM ASPIRATION SYNDROME

Meconium (MEC) is a potent inactivator of pulmonary surfactant. The authors studied the effects of polyethylene glycol addition to the exogenous surfactant over the lung mechanics and volumes. Human meconium was administrated to newborn rabbits. Animals were ventilated for 20 minutes and dynamic compliance, ventilatory pressure, and tidal volume were recorded. Animals were randomized into 3 study groups: MEC group (without surfactant therapy); S100 group (100 mg/kg surfactant); and PEG group (100 mg/kg porcine surfactant plus 5% PEG). After ventilation, a pulmonary pressure-volume curve was built. Histological analysis was carried out to calculate the mean alveolar size (Lm) and the distortion index (DI). Both groups treated with surfactant showed higher values of dynamic pulmonary compliance and lower ventilatory pressure, compared with the MEC group (P .05). S100 group had a larger maximum lung volume, V30, compared with the MEC group (P .05). Lm and DI values were smaller in the groups treated with surfactant than in the MEC group (P .05). No differences were observed between the S100 and PEG groups. Animals treated with surfactant showed significant improvement in pulmonary function as compared to nontreated animals. PEG added to exogenous surfactant did not improve lung mechanics or volumes.

Methylprednisolone improves lung mechanics and reduces the inflammatory response in pulmonary but not in extrapulmonary mild acute lung injury in mice

Objective: Gorticosteroids have been proposed to be effective in modulating the inflammatory response and pulmonary tissue remodeling in acute lung injury (ALI). We hypothesized that steroid treatment might act differently in models of pulmonary (p) or extrapulmonary (exp) ALI with similar mechanical compromise. Design: Prospective, randomized, controlled experimental study. Setting: University research laboratory. Subjects: One hundred twenty-eight BALB/c mice (20-25 g). Interventions: Mice were divided into six groups. In control animals sterile saline solution was intratracheally (0.05 mL, Cp) or intraperitoneally (0.5 mL, Gexp) injected, whereas ALI animals received Escherichia coli lipopolysaccharide intratracheally (10 mu g, ALIp) or intraperitoneally (125 mu g, ALIexp). Six hours after lipopolysaccharide administration, ALIp and ALlexp animals were further randomized into subgroups receiving saline (0.1 mL intravenously) or methylprednisolone (2 mg/kg intravenously, Mp and Mexp, respectively). Measurements and Main Results: At 24 hrs, lung state elastance, resistive and viscoelastic pressures, lung morphometry, and collagen fiber content were similar in both ALI groups. KC, interieukin-6, and transforming growth factor (TGF)-beta levels in bronchoatveolar lavage fluid, as well as tumor necrosis factor (TNF)-alpha, migration inhibitory factor (MIF), interferon (IFN)-gamma, TGF-beta 1 and TGF-beta 2 messenger RNA expression in lung tissue were higher in ALIp than in ALIexp animals. Methylprednisolone attenuated mechanical and morphometric changes, cytokine levels, and TNF-alpha, MIF, IFN gamma, and TGF-beta 2 messenger RNA expression only in ALIp animals, but prevented any changes in collagen fiber content in both ALI groups. Conclusions. Methylprednisolone is effective to inhibit fibrogenesis independent of the etiology of ALI, but its ability to attenuate inflammatory responses and lung mechanical changes varies according to the cause of ALI.

Peritumoural, but not intratumoural, lymphatic vessel density and invasion correlate with colorectal carcinoma poor-outcome markers

To evaluate whether lymphatic vessel density (LVD) and lymphatic vessel invasion (LVI) are useful markers of worse outcome in colorectal carcinoma and if LVD and LVI correlate to the classical clinical-pathological parameters, we analysed 120 cases of colorectal carcinomas selected from the files of Division of Pathology, Hospital das Clinicas, Sao Paulo University, Brazil. Assessment of LVD and LVI was performed by immunohistochemical detection of lymphatic vessels, using the monoclonal antibody D2-40. Higher LVD was found in the intratumoural area, when comparing with normal and peritumoural areas (p < 0.001). However, peritumoural LVD, but not intratumoural, correlated with both colonic-wall-invasion depth (p=0.037) and liver metastasis (p=0.012). Remarkably, LVI was found associated with local invasion (p=0.016), nodal metastasis (p=0.022) and hepatic metastasis (p < 0.001). Peritumoural LVD and LVI are directly related to histopathological variables indicative of poor outcome such as lymph-node status and liver metastasis.

Airway smooth muscle thickness in asthma is related to severity but not duration of asthma

Asthma is characterised by an increased airway smooth muscle (ASM) area (ASMarea) within the airway wall. The present study examined the relationship of factors including severity and duration of asthma to ASMarea. The perimeter of the basement membrane (PBM) and ASMarea were measured on transverse sections of large and small airways from post mortem cases of fatal (n=107) and nonfatal asthma (n=37) and from control subjects (n=69). The thickness of ASM (ASMarea/PBM) was compared between asthma groups using multivariate linear regression. When all airways were considered together, ASMarea/PBM (in millimetres) was increased in nonfatal (median 0.04; interquartile range 0.013-0.051; p=0.034) and fatal cases of asthma (0.048; 0.025-0.078; p<0.001) compared with controls (0.036; 0.024-0.042). Compared with cases of nonfatal asthma, ASMarea/PBM was greater in cases of fatal asthma in large (p<0.001) and medium (p<0.001), but not small, airways. ASMarea/PBM was not related to duration of asthma, age of onset of asthma, sex or smoking. No effect due to study centre, other than that due to sampling strategy, was found. The thickness of the ASM layer is increased in asthma and is related to the severity of asthma but not its duration.