Pseudo-equivalent deterministic excitation method application for experimental reproduction of a structural response to a turbulent boundary layer excitation.

In the transportation engineering field, the turbulent boundary layer over a structure is one of the most relevant sources of structural vibration and emitted noise. Wind tunnels are still one of the best options for vibroacoustic experimental analyses for this specific problem. However, it is also true that this experimental method is not always affordable, due to several limitations-settings hard to control, time and money consumption, discrepancies among laboratories-that wind tunnel facilities present. It has already developed different methodologies to address this necessity, most of them based on the use of loudspeakers or shakers. In this work, an existing numerical method, called the pseudo-equivalent deterministic excitation method (PEDEM), is further developed for the experimental purpose of reproducing the experimental structural response of a panel subjected to a turbulent boundary layer (TBL) excitation, by using an equivalent rain-on-the-roof excitation instead; different formulations are used for the application of this approximated TBL excitation. The experimental application of PEDEM, here called X-PEDEM, is validated by comparison with experimental results of two different panels analysed in two different wind tunnel facilities.

Endoscopic snare papillectomy: a possible radical treatment for a subgroup of T1 ampullary adenocarcinomas.

Pancreaticoduodenectomy is the standard care for invasive ampullary adenocarcinomas. However, endoscopic snare papillectomy (ESP) might play a curative role in very selected patients. We studied a series of 15 patients with T1 ampullary adenocarcinoma who were treated by ESP alone and followed up for a mean of 29.6 ± 21.9 months (range 8 - 81 months). ESP was curative for eight patients (57.1 %). No tumor-related death was observed in patients with a cancer infiltration depth of ≤ 4 mm. According to this preliminary experience, we suggest that this measurable variable threshold should be considered as a possible basis for future large-scale studies.

Elastofibroma dorsi: clinicopathological analysis of 71 cases.

INTRODUCTION: Elastofibroma dorsi (ELD) is a rare soft tissue benign tumor of the chest wall. So far, only a few large series have been reported in the English literature and, to the best of our knowledge, radiological assessment and clinical management remain without consensus. The aim of this study is to provide, on the basis of a single-institutional, homogeneous and large experience, ample evidences to support etiological and "clinical-usefulness-grade" classification hypotheses. MATERIALS AND METHODS: We report observational information on 71 ELD cases and, on the basis of these, we discuss the clinical onset features, radiological and surgical characteristics, as well as pathological and immunohistochemical evidences. RESULTS: In the period between January 1994 and September 2009, 71 consecutive patients (23 male and 48 female; mean age: 60.2 years; standard deviation [SD] ± 8.3 years) with ELD diagnosis were surgically treated at our institution. ELD was right sided in 34 patients (47.9%), left in 25 (35.2%), and bilateral in 12 (16.9%). In nine patients, ELD were diagnosed synchronously and three metachronously. Thirty-eight patients (53.5%) had no significant symptoms; 33 (46.5%) reported a clunking sensation or a localized scapular swelling during the shoulder movements. Sixty-six (93%) patients underwent surgical excision with radical intent while in five patients, a biopsy-only procedure was undertaken. Mean hospital stay was 3.0 days (SD ± 1.2 days) with a morbidity of 10.6% (one case of major postoperative bleeding requested a surgical revision of the hemostasis). At the univariate analysis, the probability of occurrence of morbidity increases with tumor size. All operated patients are alive and well at follow-up with no sign of recurrence and complete resolution of the symptomatology. CONCLUSIONS: ELD is relatively uncommon, benign, and well controlled by radical surgery.

Pulmonary malacoplakia at early stage: use of polymerase chain reaction for detection of Rhodococcus equi.

Malacoplakia is a rare inflammatory condition characterized by the accumulation of benign macrophages associated with pathognomonic Michaelis-Gutmann bodies (MGBs). It is usually found in the genito-urinary tract, and has been associated with immunocompromised states. In this short report, we present 5 patients with pulmonary nodules clinically suspicious for primary or metastatic lung cancer. The histologic examination of the surgical specimens revealed a nonspecific granulomatous chronic disease, and despite the paucity of classical MGBs, a pulmonary malacoplakia was suspected. In all cases the opportunistic pathogen Rhodococcus equi (R. equi) was identified by 16S rRNA gene sequence analysis, leading to the final pathological diagnosis of malacoplakia. We conclude that pulmonary malacoplakia associated with R. equi is a rare disease affecting also immunocompetent patients. The pathogenesis and the diagnostic problems are discussed. Since infection by R. equi is treatable, the importance of its early recognition should be emphasized.

Diffusion-weighted imaging in breast cancer: relationship between apparent diffusion coefficient and tumour aggressiveness.

AIM: To assess the utility of diffusion-weighted imaging in diagnosing and characterizing breast malignancy. MATERIALS AND METHODS: From April 2006 to April 2009, all consecutive patients with breast cancer undergoing breast magnetic resonance imaging (MRI) and subsequent surgery in our hospital were enrolled in this study. MRI was performed using a 1.5 T MRI unit using a dedicated, bilateral, four-channel breast coil. The MRI protocol included a diffusion sequence acquired using b values of 0 and 1000 s/mm(2). For each malignant lesion the relationships between tumour grade and histology and the relative value of the apparent diffusion coefficient (ADC) were analysed. RESULTS: There were 136 female patients with 162 lesions. Histology revealed 149 invasive carcinomas and 13 ductal carcinomas in situ. There were 34 grade 1, 61 grade 2, and 67 grade 3 lesions. The mean ADC value of all malignant lesions was 1.03×10(-3) mm(2)/s. The mean ADC values for invasive and in situ carcinomas were 1.03×10(-3) mm(2)/s and 1.05×10(-3) mm(2)/s, respectively. The mean ADC values for grade 1, 2, and 3 tumours were 1.25×10(-3) mm(2)/s, 1.02×10(-3) mm(2)/s, and 0.92×10(-3) mm(2)/s, respectively. A statistically significant (p<0.001) inverse correlation was disclosed between the ADC value and the tumour grading. The mean ADC value of the "less aggressive" group of disease (G1 and in situ lesions) was 1.19×10(-3) mm(2)/s, whereas the mean ADC value of the "more aggressive" group (G2-G3 invasive carcinomas) was 0.96×10(-3) mm(2)/s (p<0.001). CONCLUSION: The study confirms the usefulness of diffusion imaging in assessing the aggressiveness of breast tumours. ADC appears to be a promising parameter in the evaluation of the degree of malignancy of breast cancer tissue.

Idiopathic SIADH in young patients: don't forget the nose.

Olfactory neuroblastoma (ONB) is an uncommon neuroendocrine sinonasal cancer associated by many authors to ectopic production of several biologically active substances. We report a case of a 31-year-old male patient who presented with idiopathic syndrome of inappropriate secretion of antidiuretic hormone (SIADH). During diagnostic work-up, a CT scan of the head was performed and an ethmoidal ONB was detected. Endoscopical surgery followed by radiotherapy was carried out. Immediately after surgery natraemia levels normalised. Five years later the patient is disease-free. To our knowledge, 17 cases of SIADH associated to ONB have been published. In nine reports, idiopathic SIADH promptly led to the diagnosis of the sinonasal mass as in our clinical case, however, in many reports, correct diagnosis was accomplished months to years later. In young patients with idiopathic inappropriate antidiuretic hormone secretion, a neuroendocrine malignancy of the sinonasal area must be excluded.

Interaction of phenylisothiocyanates with the mitochondrial phosphate carrier. I. Covalent modification and inhibition of phosphate transport.

The effects of phenylisothiocyanate (PITC) and of the polar analogue p-sulfophenylisothiocyanate (p-sulfoPITC) on the phosphate carrier of bovine heart mitochondria have been investigated. Incubation of mitochondria with the two phenylisothiocyanates leads to inhibition of the phosphate carrier protein. The inhibition of phosphate transport by PITC is unaffected by the addition of dithioerythritol (DTE) or by variation of the pH. The inhibition by p-sulfoPITC is in part removed by DTE; the remaining inactivation of the phosphate carrier, which can be attributed to the reaction with NH2 groups, is temperature and pH-dependent. Inhibition of phosphate transport by both p-sulfoPITC and PITC depends on the time of incubation and the concentration of the inhibitor. Preincubation with mersalyl protects the carrier protein against the inactivation by p-sulfoPITC but not against PITC. Other SH reagents tested do not show any protective effect. It can thus be concluded that two types of lysine residues are essential for the activity of the phosphate carrier. Lysine(s) of the former type are located at the surface of the membrane and are topologically related to the functional SH groups of the protein. Lysine residue(s) of the latter type are buried in the hydrophobic phase of the membrane.

The use of fluorescein-dipalmitoylphosphatidylethanolamine for measuring pH-changes in the internal compartment of phospholipid vesicles.

The synthesis and characterisation of fluorescein-phosphatidylethanolamine (FPE) is described. The effects of dielectric constant, ionic strength and ambient pH upon the optical absorbance properties of FPE are presented. It is shown that under appropriate conditions, FPE rapidly and quantitatively reports the pH of the aqueous bulk phases when incorporated into phospholipid vesicles. It is also shown that, when the external medium is highly buffered, FPE is capable of specificity reporting only the pH of the intravesicular compartment. The application of FPE for studies of intravesicular pH changes of reconstituted membranous protein systems is discussed.

A multidisciplinary approach to the study of cultural heritage environments: Experience at the Palatina Library in Parma.

The aim of this paper is to describe a multidisciplinary approach including biological and particle monitoring, and microclimate analysis associated with the application of the Computational Fluid Dynamic (CFD). This approach was applied at the Palatina historical library in Parma. Monitoring was performed both in July and in December, in the absence of visitors and operators. Air microbial monitoring was performed with active and passive methods. Airborne particles with a diameter of ≥0.3, ≥0.5, ≥1 and ≥5 µm/m3, were counted by a laser particle counter. The surface contamination of shelves and manuscripts was assessed with nitrocellulose membranes. A spore trap sampler was used to identify both viable and non-viable fungal spores by optical microscope. Microbiological contaminants were analyzed through cultural and molecular biology techniques. Microclimatic parameters were also recorded. An infrared thermal camera provided information on the surface temperature of the different building materials, objects and components. Transient simulation models, for coupled heat and mass-moisture transfer, taking into account archivist and general public movements, combined with the related sensible and latent heat released into the environment, were carried out applying the CFD-FE (Finite Elements) method. Simulations of particle tracing were carried out. A wide variability in environmental microbial contamination, both for air and surfaces, was observed. Cladosporium spp., Alternaria spp., Aspergillus spp., and Penicillium spp. were the most frequently found microfungi. Bacteria such as Streptomyces spp., Bacillus spp., Sphingomonas spp., and Pseudoclavibacter as well as unculturable colonies were characterized by molecular investigation. CFD simulation results obtained were consistent with the experimental data on microclimatic conditions. The tracing and distribution of particles showed the different slice planes of diffusion mostly influenced by the convective airflow. This interdisciplinary research represents a contribution towards the definition of standardized methods for assessing the biological and microclimatic quality of indoor cultural heritage environments.

(1S)-1-(aminomethyl)-2-(arylacetyl)-1,2,3,4-tetrahydroisoquinoline and heterocycle-condensed tetrahydropyridine derivatives: members of a novel class of very potent kappa opioid analgesics.

The synthesis and structure-activity relationship (SAR) of a novel class of kappa opioid analgesics, 1-(aminomethyl)-2-(arylacetyl)-1,2,3,4- tetrahydroisoquinolines and (aminomethyl)-N-(arylacetyl)-4,5,6,7-tetrahydrothienopyridines+ ++, are described. These compounds, formally derived by the condensation of a benzene or thiophene ring on the piperidine nucleus of the recently described compounds 1, are from 3 to 7 times more potent as antinociceptive agents and with a longer duration of action than the original lead compounds. A similar N2-C1-C9-N10 pharmacophore torsional angle of approximately 60 degrees was also found for this class of compounds by using X-ray and 1H NMR analyses. The same absolute configuration (S) at the chiral center of the active (-) enantiomers was determined by X-ray crystallographic analysis. A varied degree of kappa receptor selectivity was a feature of this novel class of antinociceptive agents (mu/kappa ratio from 44 to 950 according to the nature of the basic moiety). SAR analysis indicated that the presence of electron-withdrawing and lipophilic substituents in para and/or meta positions in the arylacetic moiety and the pyrrolidino or dimethylamino basic groups are required to optimize biological activity. The lead compounds 28, 30, and 48 are among the most potent antinociceptive agents (ED50 ca. 0.020 microM/kg sc) and kappa ligands (Ki(kappa) ca. 0.20 nM) identified so far.

Substituted 1-(aminomethyl)-2-(arylacetyl)-1,2,3,4-tetrahydroisoquinolines: a novel class of very potent antinociceptive agents with varying degrees of selectivity for kappa and mu opioid receptors.

This study describes the synthesis of a series of novel substituted 1-(aminomethyl)-2-(arylacetyl)-1,2,3,4-tetrahydroisoquinolines, and discusses their structure-activity relationships (SARs) using binding affinity for opioid receptors and antinociceptive potency as the indices of biological activity. The introduction of a hydroxy substituent in position 5 of the isoquinoline nucleus generated a compound, 40, which is 2 times more potent than the previously disclosed unsubstituted analogue 39 in mouse models of antinociception. A QSAR analysis of the 5-substitution clearly demonstrates that antinociceptive activity is inversely associated with the lipophilicity of the substituents. The substituted compounds described herein are less selective for the kappa opioid receptors than the unsubstituted isoquinoline 39. For example, the 5-hydroxy-substituted compound 59 shows high affinity for kappa opioid receptors (Ki kappa = 0.09 nM) and a Ki mu/Ki kappa ratio of only 5. However, a multiple linear regression analysis demonstrates a lack of correlation between antinociceptive activity and affinity for the mu opioid receptor. On the other hand, the correlation between binding affinity to kappa opioid receptor and antinociceptive activity was statistically significant.

Selective kappa-opioid agonists: synthesis and structure-activity relationships of piperidines incorporating on oxo-containing acyl group.

This study describes the synthesis and the structure-activity relationships (SARs) of the (S)-(-)-enantiomers of a novel class of 2-(aminomethyl)piperidine derivatives, using kappa-opioid binding affinity and antinociceptive potency as the indices of biological activity. Compounds incorporating the 1-tetralon-6-ylacetyl residue (30 and 34-45) demonstrated an in vivo antinociceptive activity greater than predicted on the basis of their kappa-binding affinities. In particular, (2S)-2-[(dimethylamino)methyl]-1-[(5,6,7,8-tetrahydro-5-oxo-2- naphthyl)acetyl]piperidine (34) was found to have a potency similar to spiradoline in animal models of antinociception after subcutaneous administration, with ED50s of 0.47 and 0.73 mumol/kg in the mouse and in the rat abdominal constriction tests, respectively. Further in vivo studies in mice and/or rats revealed that compound 34, compared to other selective kappa-agonists, has a reduced propensity to cause a number of kappa-related side effects, including locomotor impairment/sedation and diuresis, at antinociceptive doses. For example, it has an ED50 of 26.5 mumol/kg sc in the rat rotarod model, exhibiting a ratio of locomotor impairment/sedation vs analgesia of 36. Possible reasons for this differential activity and its clinical consequence are discussed.

Discovery of a novel class of substituted pyrrolooctahydroisoquinolines as potent and selective delta opioid agonists, based on an extension of the message-address concept.

This paper describes the design and synthesis of compounds belonging to a novel class of substituted pyrrolooctahydroisoquinolines which are potent and selective delta opioid agonists. Molecular modeling studies performed on known, selective delta ligands such as (+)-3 and the potent delta agonists SNC 80 led to the identification of the carboxamido moiety of the latter as a putative nonaromatic delta address. Insertion of this moiety onto the octahydroisoquinoline opioid message resulted in (+/-)-5b, a potent and selective delta ligand. The active enantiomer, (-)-5b, displayed nanomolar affinity for the delta receptor (Ki = 0.9 nM) with good mu/delta and kappa/delta binding selectivity ratios (140 and 1480, respectively). In addition, (-)-5b behaved as a full delta agonist in the mouse vas deferens bioassay having an IC50 = 25 nM and being antagonised in the presence of 30 nM naltrindole (NTI). These studies, based on the message-address concept, indicated that the nonaromatic (N,N-diethylamino)carbonyl moiety is a viable alternative to the classical benzene ring as a delta opioid address. Preliminary in vivo studies showed that (+/-)-5b produced a dose-related antinociception in the mouse abdominal constriction test after intracerebroventricular administration (ED50 = 1.6 micrograms/mouse).

Listeria monocytogenes infection of Caco-2 cells: role of growth temperature.

The aim of the present study was to evaluate the role of temperature in the virulence of Listeria monocytogenes, a Gram-positive facultative intracellular food-borne pathogen. The capacity of bacteria grown at 37, 25 and 4 degrees C to develop haemolytic activity, to enter the Caco-2 enterocyte-like cell line and to multiply intracellularly was investigated. We demonstrated that L. monocytogenes penetration was not significantly influenced by the growth temperature of cultures and that bacteria grown at low temperature were capable of synthesizing internalin and, during the infection process, of restoring the haemolytic phenotype which is normally lacking in the extracellular environment at 4 and 25 degrees C. It can be concluded that L. monocytogenes, frequently present in numerous environmental sources and also in refrigerated food products, produces at low temperature, the virulence factors necessary to invade intestinal cells.

Modulation of actA gene expression in Listeria monocytogenes by iron.

This study analysed the invasiveness of Listeria monocytogenes into enterocyte-like Caco-2 cells in which iron depletion was achieved by picolinic acid treatment. Both entry and intracellular multiplication varied depending on the endogenous iron content of bacterial and eukaryotic cells. The behaviour within enterocytes was correlated with a 10-fold increased transcription of the actA gene observed in bacterial cells grown under conditions of iron stress.

The effects of inhibitors of vacuolar acidification on the release of Listeria monocytogenes from phagosomes of Caco-2 cells.

To evaluate the role of the acidic pH of phagosomes on the invasive ability and fate of Listeria monocytogenes within host cells, entry and replication of this gram-positive bacterium in a human enterocyte-like cell line (Caco-2) were investigated by a combination of biochemical and ultrastructural approaches. The effects of inhibitors of vacuolar acidification--the lipophilic weak base ammonium chloride, the carboxylic ionophore monensin and the vacuolar proton ATPase inhibitor bafilomycin A1--on the bacterial invasion pathway were analysed. These agents, which raise the intracellular vesicle acidic pH of living cells by different mechanisms, affected L. monocytogenes replication in Caco-2 cells. Bacteria internalised by bafilomycin-treated cells were unable to escape from phagosomes, as demonstrated by electronmicroscopy. The results provide evidence that low pH is required for efficient intracellular growth of L. monocytogenes.

Infection of human enterocyte-like cells with rotavirus enhances invasiveness of Yersinia enterocolitica and Y. pseudotuberculosis.

Mixed infection with rotavirus and either Yersinia enterocolitica or Y. pseudotuberculosis was analysed in Caco-2 cells, an enterocyte-like cell line highly susceptible to these pathogens. Results showed an increase of bacterial adhesion and internalisation in rotavirus-infected cells. Increased internalisation was also seen with Escherichia coli strain HB101 (pRI203), harbouring the inv gene from Y. pseudotuberculosis, which is involved in the invasion process of host cells. In contrast, the superinfection with bacteria of Caco-2 cells pre-infected with rotavirus resulted in decreased viral antigen synthesis. Transmission electron microscopy confirmed the dual infection of enterocytes. These data suggest that rotavirus infection enhances the early interaction between host cell surfaces and enteroinvasive Yersinia spp.

Antinociceptive effects of non-steroidal anti-inflammatory drugs in a rat model of unilateral hindpaw inflammation.

The antinociceptive activity of intramuscular 6-methoxy-2-naphthylacetic acid (6-MNA), the active metabolite of nabumetone, was examined in a rat model of unilateral hindpaw inflammation/hyperalgesia and compared with that of three other non-steroidal anti-inflammatory drugs (NSAIDs)--diclofenac, naproxen and piroxicam. Over a dose range of 10-100 mg/kg i.m., 6-MNA produced a dose-dependent increase in the withdrawal threshold to a noxious mechanical stimulus applied to the inflamed paw; however, a higher dose (300 mg/kg) produced no further increase in antinociceptive activity. Peak effects occurred 30 min after intramuscular injection. Diclofenac, naproxen and piroxicam produced antinociceptive effects that were qualitatively similar to those of 6-MNA. There was an indication of quantitative differences between the four NSAIDs in terms of potency and efficacy although this was not statistically significant. The rapid onset of effect and the lack of correlation between the relative antinociceptive effects of the four NSAIDs and the anti-inflammatory activities (assayed as inhibition of carrageenan-induced rat paw oedema) suggest that their pain relieving properties may not be entirely the result of their anti-inflammatory effects. These experimental data support the therapeutic value of 6-MNA as an analgesic in conditions of inflammatory pain.