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Delphine Jouin,Nadège Blanchard,Eliane Alexandre,Frédéric Delobel,Pascale David-Pierson,Thierry Lavé,Daniel Jaeck,Lysiane Richert,Philippe Coassolo Hepatocyte assays, routinely used to assess the metabolic stability of new chemical entities, were recently improved by using hepatocytes in suspension instead of primary cultures [N. Blanchard, L. Richert, B. Notter, F. Delobel, P. David, P. Coassolo, T. Lavé, Impact of serum on clearance predicti... ( view more )ons obtained from suspensions and primary cultures of rat hepatocytes, Eur. J. Pharm. Sci. 23 (2004) 189-199]. The aim of the present study was to investigate miniaturising the suspension assay by using cryopreserved human hepatocytes, i.e., 150,000 cells/well in 96-well plates, to predict hepatic clearance (CLH) in order to increase compound throughput and decrease cost and tissue requirements. For this, an evaluation was first carried out with rat hepatocytes. Then, human hepatocytes from various donors were used under these predetermined conditions, either immediately after isolation, either after a 20-h-cold storage period in UW or after cryopreservation. The values of CLint and CLH determined using human hepatocytes in suspension in 96-well plates, immediately after isolation, after cold storage or after cryopreservation, were comparable to those obtained with hepatocytes in primary culture. In particular, the use of cryopreserved human hepatocytes in suspension in a 96-well format appeared to be largely satisfactory as a tool for screening and ranking of compounds in the early phase of the drug discovery process. ( view less ) I Marco,E Ferroglio,J R López-Olvera,J Montané,S LavínAntibodies to Neospora caninum were determined in the red fox (Vulpes vulpes) in the Pyrenees, north-eastern Spain. Sera from 53 red foxes (29 male and 24 female) were tested using a Neospora agglutination test (NAT). Seroprevalence at dilutions of 1/40, 1/80 and 1/160 was 69.8%, 47.2% and 7.5%, re... ( view more )spectively. Sex differences were significant only at a dilution of 1:40. The high seroprevalence observed in red fox suggests that this species is highly exposed to N. caninum in this area. ( view less ) J Pitarch-Ruiz,A Sánchez de Merás,J Sánchez-Marín,A M Velasco,C Lavín,I MartínVertical excitation energies belonging to some different Rydberg series of hydrogen chloride have been determined with a coupled-cluster theoretical approach. These excitation energies have allowed us to calculate electric dipole transition intensities in HCl and allow additional assessment of the ... ( view more )calculation approach presently used to provide an adequate description of the valence and Rydberg states of HCl. The molecular quantum defect orbital has been applied to the calculation of oscillator strengths. In particular, new insight is given on the assignment of states as the R1Pi, the 1Delta(4dpi and 5ppi), the 1Sigma+(4dpi), and the nddelta(1Pi, 1Phi) and 4f states. ( view less ) William E Higgins,James P Helferty,Kongkuo Lu,Scott A Merritt,Lav Rai,Kun-Chang Yu Bronchoscopic biopsy of the central-chest lymph nodes is an important step for lung-cancer staging. Before bronchoscopy, the physician first visually assesses a patient's three-dimensional (3D) computed tomography (CT) chest scan to identify suspect lymph-node sites. Next, during bronchoscopy, the ... ( view more )physician guides the bronchoscope to each desired lymph-node site. Unfortunately, the physician has no link between the 3D CT image data and the live video stream provided during bronchoscopy. Thus, the physician must essentially perform biopsy blindly, and the skill levels between different physicians differ greatly. We describe an approach that enables synergistic fusion between the 3D CT data and the bronchoscopic video. Both the integrated planning and guidance system and the internal CT-video registration and fusion methods are described. Phantom, animal, and human studies illustrate the efficacy of the methods. ( view less ) Marina Y Dolina,Duane C Cornish,Scott A Merritt,Lav Rai,Rickhesvar Mahraj,William E Higgins,Rebecca Bascom BACKGROUND: Endobronchial path selection is important for the bronchoscopic diagnosis of focal lung lesions. Path selection typically involves mentally reconstructing a three-dimensional path by interpreting a stack of two-dimensional (2D) axial plane CT scan sections. The hypotheses of our study a... ( view more )bout path selection were as follows: (1) bronchoscopists are inaccurate and overly confident when making endobronchial path selections based on 2D CT scan analysis; and (2) path selection accuracy and confidence improve and become better aligned when bronchoscopists employ path-planning methods based on virtual bronchoscopy (VB). METHODS: Studies of endobronchial path selection comparing three path-planning methods (ie, the standard 2D CT scan analysis and two new VB-based techniques) were performed. The task was to navigate to discrete lesions located between the third-order and fifth-order bronchi of the right upper and middle lobes. Outcome measures were the cumulative accuracy of making four sequential path selection decisions and self-reported confidence (1, least confident; 5, most confident). Both experienced and inexperienced bronchoscopists participated in the studies. RESULTS: In the first study involving a static paper-based tool, the mean (+/- SD) cumulative accuracy was 14 +/- 3% using 2D CT scan analysis (confidence, 3.4 +/- 1.3) and 49 +/- 15% using a VB-based technique (confidence, 4.2 +/- 1.1; p = 0.0001 across all comparisons). For a second study using an interactive computer-based tool, the mean accuracy was 40 +/- 28% using 2D CT scan analysis (confidence, 3.0 +/- 0.3) and 96 +/- 3% using a dynamic VB-based technique (confidence, 4.6 +/- 0.2). Regardless of the experience level of the bronchoscopist, use of the standard 2D CT scan analysis resulted in poor path selection accuracy and misaligned confidence. Use of the VB-based techniques resulted in considerably higher accuracy and better aligned decision confidence. CONCLUSIONS: Endobronchial path selection is a source of error in the bronchoscopy workflow. The use of VB-based path-planning techniques significantly improves path selection accuracy over use of the standard 2D CT scan section analysis in this simulation format. ( view less ) Edenir Inêz Palmero,Lavínia Schüler-Faccini,Maira Caleffi,Maria Isabel Waddington Achatz,Magali Olivier,Ghyslaine Martel-Planche,Virginie Marcel,Ernestina Aguiar,Juliana Giacomazzi,Ingrid Petroni Ewald,Roberto Giugliani,Pierre Hainaut,Patricia Ashton-Prolla Germline TP53 mutations predispose to a rare familial cancer syndrome, the Li-Fraumeni Syndrome (LFS), characterized by the early onset of multiple cancers including childhood adrenocortical carcinomas, sarcomas and brain tumors, and breast and colon cancer in young adults. An identical germline mu... ( view more )tation at codon 337 in TP53 (R337H) has been shown to be causally related to an increased risk of multiple cancers in unrelated subjects with familial cancer risk in Southern Brazil. Here we have assessed the prevalence of R337H in 750 healthy women participating in a community-based breast cancer screening program in the area of Porto Alegre. The mutant was detected in two participants (0.3%) who were fourth-degree relatives and reported a familial history of cancer at multiple sites that did not match classical criteria for LFS and its variants. Testing in additional family members detected the mutation in three subjects, one of whom developed breast cancer at the age of 36. These findings indicate that R337H may be a low penetrance mutant which predisposes to multiple cancers and occurs in the population of Southern Brazil at a frequency 10-20 times higher than other TP53 mutants commonly associated with LFS. ( view less ) Ignasi Marco,Rosa Rosell,Oscar Cabezón,Gregorio Mentaberre,Encarna Casas,Roser Velarde,Jorge Ramón López-Olvera,Ana Hurtado,Santiago Lavín In 2001 and 2002, an outbreak of a previously unreported disease, associated with a border disease virus (BDV), caused high mortality in the Southern chamois (Rupicapra pyrenaica) population in the Alt Pallars-Aran National Hunting Reserve in the Catalan Pyrenees (NE Spain). Between 2002 and 2006, ... ( view more )sera and/or tissue samples taken from 116 healthy chamois shot during the hunting season, plus 42 from chamois affected by different diseases, were studied. A blocking enzyme-immunosorbent assay (ELISA) was used to study pestivirus seroprevalence in 114 healthy hunted and 31 diseased chamois, yielding positive results in 73.7 and 22.6% of the chamois, respectively. Comparative virus neutralization tests (VNT) performed on 42 seropositive samples with 6 pestivirus strains yielded statistically higher titres to BDV Spain 97, followed by BDV chamois, BDV 137/4, BDV Moredun, Bovine Diarrhoea virus-1 (BVDV-1) NADL and BVDV-2 atypical. Virological investigations for pestivirus detection were performed using an antigen ELISA test in 82 healthy and 18 diseased chamois, RT-PCR in 16 healthy and in all diseased chamois, and virus isolation in 14 diseased chamois. No viral antigen was detected in any of the healthy animals. A pestivirus, characterized as BDV by monoclonal antibodies, was detected in the 10 chamois showing clinical signs consistent with BDV infection. Sequence analysis in the 5' untranslated region (5'-UTR) revealed that they were grouped into the BDV-4 genotype. In the remaining chamois, infectious keratoconjunctivitis, pneumonia, trauma and contagious ecthyma were diagnosed. The cause of death was unknown in five chamois. The results suggest that the infection has become endemic in the population and that it could have a significant impact on chamois population dynamics. ( view less ) Lenice Minussi,Renate Mohrdieck,Marilina Bercini,Tani Ranieri,Maria Teresa Vieira Sanseverino,Wakana Momino,Sidia Maria Callegari-Jacques,Lavínia Schuler-Faccini The rubella virus is a potent human teratogen. The highest risk of this infection occurs during pregnancy, as the virus may cause fetal damage known as congenital rubella syndrome (CRS). Since the rubella vaccine is made with attenuated live virus, there is a high level of anxiety concerning exposu... ( view more )re during pregnancy. Although no case of CRS has been proved in children of immunized susceptible pregnant women, a risk below 1.6% cannot be ruled out. Our main purpose was to evaluate the occurrence of CRS in women who were vaccinated against rubella and did not know that they were pregnant, or became pregnant within 30 days after vaccination. We collected, prospectively, data on 171 pregnant women who were susceptible at the time of vaccination and compared them with data on the total population of pregnant women in the state of Rio Grande do Sul (RS), Brazil. A serologic sample was collected in 149 infants of susceptible mothers. A total of 10 infants (6.7%) had anti-rubella antibodies. When these were compared with the results obtained in the total population of births in RS, no difference was found in mean birth weight, low birth weight and sex. None of the ten infants with IgM(+) presented congenital defects involving CRS, during the physical examinations performed at the time of birth and at 3 months of age. Our study allows the safety of rubella vaccination to be extended to pregnant women. ( view less ) Angel Ferrer,Angel J Huertas,Carlos H Larramendi,Jose L García-Abujeta,Joan Bartra,Jose R Lavín,Carmen Andreu,Juan A Pagán,María A López-Matas,Enrique Fernández-Caldas,Jerónimo Carnés ABSTRACT: BACKGROUND: Commercial available skin prick test with fruits can be negative in sensitized or allergic patients due to a reduction in biological activity during the manufacturing process. Prick-prick tests with fresh foods are often preferred, but they are a non-standardized procedure. Th... ( view more )e usefulness of freeze-dried extracts of Canary Islands tomatoes, comparing the wheal sizes induced by prick test with the prick-prick method in the diagnosis of tomato sensitization has been analyzed.The objective of the study was to assess the potential diagnostic of freeze-dried extracts of Canary Islands tomatoes, comparing the wheal sizes induced by prick test with the prick-prick method. METHODS: Two groups of patients were analyzed: Group I: 26 individuals reporting clinical symptoms induced by tomato contact or ingestion. Group II: 71 control individuals with no symptoms induced by tomato: 12 of them were previously skin prick test positive to a tomato extract, 39 were atopic and 20 were non-atopic. All individuals underwent prick-prick with fresh ripe peel Canary tomatoes and skin prick tested with freeze-dried peel and pulp extracts obtained from peel and pulp of Canary tomatoes at 10 mg/ml. Wheal sizes and prick test positivity (>/= 7 mm2) were compared between groups. RESULTS: In group I, 21 (81%) out of 26 patients were prick-prick positive. Twenty patients (77%) had positive skin prick test to peel extracts and 12 (46%) to pulp extracts. Prick-prick induced a mean wheal size of 43.81 +/- 40.19 mm2 compared with 44.25 +/- 36.68 mm2 induced by the peel extract (Not significant), and 17.79 +/- 9.39 mm2 induced by the pulp extract (p < 0.01).In group II, 13 (18%) out of 71 control patients were prick-prick positive. Twelve patients (all of them previously positive to peel extract) had positive skin prick test to peel and 3 to pulp. Prick-prick induced a mean wheal size of 28.88 +/- 13.12 mm2 compared with 33.17 +/- 17.55 mm2 induced by peel extract (Not significant), and 13.33 +/- 4.80 mm2 induced by pulp extract (p < 0.05 with peel extract and prick-prick). CONCLUSION: Canary peel tomato extract seems to be as efficient as prick-prick tests with ripe tomatoes to diagnose patients sensitized to tomato. The wheal sizes induced by prick-prick and peel extracts were very similar and showed a high correlation coefficient. ( view less ) C H Larramendi,A Ferrer,A J Huertas,J L García-Abujeta,C Andreu,R Tella,M T Cerdà,J Bartra,J R Lavín,J A Pagán,M A López-Matas,E Fernández-Caldas,J Carnés BACKGROUND: Tomatoes (Lycopersicon esculentum) are consumed world-wide. The prevalence of sensitization to tomatoes remains unknown. OBJECTIVE: To determine the prevalence of skin test reactivity to tomato and to describe the characteristics of tomato-sensitized subjects. METHODS: Individuals atten... ( view more )ding for the first time during the period of the study to six Allergy centres, located along the Mediterranean coast of Spain, reporting respiratory and/or cutaneous symptoms, were included. All patients were skin prick tested with a battery of inhalant allergens and with peel and pulp of Canary tomato extracts. RESULTS: The study included 1734 individuals (757 males, 977 females; 31.9+/-17.8 years old). The prevalence of sensitization to tomato was 6.52% (113 patients; 65 males, 48 females; 29.5+/-13 years old). The peel extract was positive in 110 patients and the pulp extract in 47 patients; three patients were positive exclusively to pulp. Only 1.8% of individuals reported symptoms with tomato; 44% of them had skin test negative to both extracts. Among tomato-sensitized subjects, 16% reported symptoms with tomato, 97% were sensitized to inhalant aeroallergens, including 84% to pollens (mainly Artemisia vulgaris and Platanus hybrida), with differences between Northern and Southern centres. CONCLUSIONS: The prevalence found of skin test sensitivity to tomato is high. Peel extracts detected most of the sensitized subjects. Most of the sensitized subjects were asymptomatic and some patients reported symptoms without skin test sensitivity. Positive subjects were very frequently sensitized to pollens, suggesting allergen cross-reactivity. Regional differences may exist, possibly related to the pattern of sensitization to cross-reacting pollens. ( view less ) P-H Blard,J Lavé,R Pik,P Wagnon,D Bourlès The magnitude of atmospheric cooling during the Last Glacial Maximum and the timing of the transition into the current interglacial period remain poorly constrained in tropical regions, partly because of a lack of suitable climate records. Glacial moraines provide a method of reconstructing past te... ( view more )mperatures, but they are relatively rare in the tropics. Here we present a reconstruction of atmospheric temperatures in the central Pacific during the last deglaciation on the basis of cosmogenic 3He ages of moraines and numerical modelling of the ice cap on Mauna Kea volcano, Hawaii--the only highland in the central Pacific on which moraines that formed during the last glacial period are preserved. Our reconstruction indicates that the Last Glacial Maximum occurred between 19,000 and 16,000 years ago in this region and that temperatures at high elevations were about 7 degrees C lower than today during this interval. Glacial retreat began about 16,000 years ago, but temperatures were still about 6.5 degrees C lower than today until 15,000 years ago. When combined with estimates of sea surface temperatures in the central Pacific Ocean, our reconstruction indicates that the lapse rate during the Last Glacial Maximum was higher than at present, which is consistent with the proposal that the atmosphere was drier at that time. Furthermore, the persistence of full glacial conditions until 15,000 years ago is consistent with the relatively late and abrupt transition to warmer temperatures in Greenland, indicating that there may have been an atmospheric teleconnection between the central Pacific and North Atlantic regions during the last deglaciation. ( view less ) Ana Luisa Valente,Ignasi Marco,Maria Angeles Zamora,Maria Luz Parga,Santiago Lavín,Ferran Alegre,Rafaela Cuenca This study aimed to provide the normal radiographic anatomic appearance of the limbs of the loggerhead sea turtle, Caretta caretta. Dorsopalmar and dorsoplantar radiographs were taken of the forelimbs and hindlimbs of 15 juvenile and 15 subadult loggerhead sea turtles, 17 alive and 13 dead. For com... ( view more )parison, computed tomographic, gross anatomic, osteologic, and histologic studies were performed on the limbs of 5 of the sea turtles. Bones from the distal part of the fore and hind flippers were seen in detail with a mammographic film-screen combination. The pectoral and pelvic girdles, superimposed by the carapace, were better seen on standard radiographs with the use of rare-earth intensifying screens. Mammographic radiographs of the manus of 5 small juvenile turtles showed active growth zones. Visualization of bone contours in the distal part of the limbs was clearer than in mammals owing to the very few superimpositions. The presence of a substantial amount of cartilage in the epiphyses produced better visibility of limb ends. We conclude that use of a mammography film-screen combination is the best way to evaluate the bony and joint structures of the limbs of sea turtles. Radiography provides reliable images for clinical purposes. Considering the low cost and logistics of this technique, it is a practical ancillary test for marine animal rehabilitation centers to use. ( view less ) Alex Kasrayan,Marco Bocola,Anders G Sandström,Gaston Lavén,Jan-E BäckvallA number of model structures of the CalA suggested by comparative modeling were tested by site-directed mutagenesis. Enzyme variants were created where amino acids predicted to play key roles for the lipase activity in the different models were replaced by an inert amino acid (alanine). The results... ( view more ) from activity measurements of the overproduced and purified mutant enzymes indicate a structure where the active site consists of amino acid residues Ser184, His366, and Asp334 and in which there is no lid. This model can be used for future targeted modifications of the enzyme to obtain new substrate acceptance, better thermostability, and higher enantioselectivity. ( view less ) Paulo I Homem de Bittencourt,Denise J Lagranha,Alexandre Maslinkiewicz,Sueli M Senna,Angela M V Tavares,Lisiane P Baldissera,Daiane R Janner,Joelso S Peralta,Patrícia M Bock,Lucila L P Gutierrez,Gustavo Scola,Thiago G Heck,Maurício S Krause,Lavínia A Cruz,Dulcinéia S P Abdalla,Cláudia J Lagranha,Thais Lima,Rui Curi Atherosclerosis is a multifactorial inflammatory disease of blood vessels which decimates one in every three people in industrialized world. Despite the important newest clinical approaches, currently available strategies (e.g. nutritional, pharmacological and surgical) may only restrain the worsen... ( view more )ing of vascular disease. Since antiproliferative cyclopentenone prostaglandins (CP-PGs) are powerful anti-inflammatory agents, we developed a negatively charged liposome-based pharmaceutical formulation (LipoCardium) that specifically direct CP-PGs towards the injured arterial wall cells of atherosclerotic mice. In the blood stream, LipoCardium delivers its CP-PG contents only into activated arterial wall lining cells due to the presence of antibodies raised against vascular cell adhesion molecule-1 (VCAM-1), which is strongly expressed upon inflammation by endothelial cells and macrophage-foam cells as well. After 4 months in a high-lipid diet, all low-density lipoprotein receptor-deficient adult control mice died from myocardium infarction or stroke in less than 2 weeks, whereas LipoCardium-treated (2 weeks) animals (still under high-lipid diet) completely recovered from vascular injuries. In vitro studies using macrophage-foam cells suggested a tetravalent pattern for LipoCardium action: anti-inflammatory, antiproliferative (and pro-apoptotic only to foam cells), antilipogenic and cytoprotector (via heat-shock protein induction). These astonishing cellular effects were accompanied by a marked reduction in arterial wall thickness, neointimal hyperplasia and lipid accumulation, while guaranteed lifespan to be extended to the elderly age. Our findings suggest that LipoCardium may be safely tested in humans in a near future and may have conceptual implications in atherosclerosis therapy. ( view less ) R Marco,D A Laván,J J W A van Loon,L J Leandro,O J Larkin,C Dijkstra,P Anthony,A Villa,M R Davey,K C Lowe,J B Power,F J MedinaA key requirement to enhance our understanding of the response of biological organisms to different levels of gravity is the availability of experimental systems that can simulate microgravity and hypergravity in ground-based laboratories. This paper compares the results obtained from analysing gen... ( view more )e expression profiles of Drosophila in space versus those obtained in a random position machine (RPM) and by centrifugation. The correlation found validates the use of the RPM simulation technique to establish the effects of real microgravity on biological systems. This work is being extended to investigate Drosophila development in another gravity modifying instrument, the levitation magnet. ( view less ) J Montané,I Marco,J R López-Olvera,L Rossi,X Manteca,S Lavín The differences between the capture stress responses of captive and free-ranging roe deer (Capreolus capreolus) and their modulation by acepromazine, during a period of three hours' physical restraint after capture in drive-nets, were examined in 16 free-ranging and 16 captive roe deer. Eight of th... ( view more )e free-ranging and eight of the captive animals received acepromazine intramuscularly, and the other eight free-ranging and eight captive deer received the same volume of saline. Heart rate, body temperature and haematological and serum biochemical parameters were analysed. In the groups treated with acepromazine, the heart rate stabilised sooner, and the red blood cell (RBC) count, haemoglobin concentration, packed-cell volume, the serum activities of creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) and the concentrations of creatinine and lactate were significantly lower, and serum glucose started to decrease earlier, than in the untreated groups. Serum potassium levels decreased over time only in the untreated groups. The body temperature stabilised earlier, and the RBC count, haemoglobin concentration, serum CK, AST, ALT and LDH activities, and serum creatinine, lactate, cholesterol and glucose concentrations were significantly lower in the free-ranging roe deer than in the captive deer. ( view less ) I Lavín Castejón,J Mut Oltra,C Trillo Balizón,A Maldonado BarrionuevoCowden's disease is a rare genodermatosis that is characterized for multiple cutaneous and visceral hamartoma . Lhermitte-Duclos's disease is a cerebelous lesion that consists in the displasic enlargement of the cerebelous circumvolution. It's incluyed in phacomatosis and usually presents associate... ( view more )d to Cowden's disease, tuberous sclerosis and overlap syndromes.A 56 years old man, diagnosed in Dermatology with Cowden's disease ten years ago. In the extension study, he had hamartoma intestinal polip, esophagic glucogenic acanthosis and two solid thyroid nodules. The craneal TC didn't show significant alteration. Ten years after diagnosis a cerebral magnetis resonance was performed for intense cephalea, and it was found a bad-defined mass in right cerebelous hemisphere without contrast captation, compatible with cerebelous glangliocytoma. ( view less ) Karyn B Stitzenberg,Nancy Klauber-Demore,Xiao Sha Chang,Benjamin F Calvo,David W Ollila,Lav K Goyal,Michael O Meyers,Hong Jin Kim,Joel E Tepper,Carolyn I Sartor INTRODUCTION: Intraoperative radiotherapy (IORT) has the potential to eliminate the access problems associated with standard 6-week post-operative external beam radiotherapy for patients with breast cancer. However, accurate delivery of the IORT dose for breast cancer has been problematic due to di... ( view more )fficulty estimating the tumor bed after tumor removal and tissue re-approximation. We are investigating the feasibility of partial breast irradiation using a single fraction of IORT delivered to the tumor in vivo prior to surgical resection. METHODS: In a trial, approved by the University of North Carolina School of Medicine Institutional Review Board, patients > or =55 years old with infiltrating ductal carcinoma without an extensive intraductal component with an overall tumor size < or =3.0 cm receive a single dose of IORT in place of standard post-operative radiotherapy. RESULTS: All patients undergo preoperative ultrasonography to define the target volume. In a standard operating room, the tumor is exposed through a standard partial mastectomy incision. IORT is then delivered using a mobile, self-shielded, magnetron-driven X-band linear accelerator (Intraop Corp, Santa Clara, CA, USA). 15 Gy is delivered to the 90% isodose line covering the tumor with a 1 cm margin anterior-posterior and 2 cm margins laterally. After IORT, partial mastectomy is performed in the usual manner. CONCLUSIONS: IORT for breast cancer, delivered to the exposed tumor in vivo, is feasible and allows accurate estimation of the tumor bed. Further follow-up is ongoing to determine the efficacy of this approach. ( view less ) Abigail S Caudle,Joel E Tepper,Benjamin F Calvo,Michael O Meyers,Lav K Goyal,William G Cance,Hong Jin Kim INTRODUCTION: Retroperitoneal sarcomas (RPS) remain a therapeutic challenge due to high local recurrence rates. Preoperative RT offers theoretical advantages in the multidisciplinary care of RPS. The purpose of our study was to evaluate our experience using preoperative radiotherapy (PRT) in the tr... ( view more )eatment of RPS. METHODS: This is a single-institution review of patients with RPS treated with PRT from 1994 until 2004. Three radiation oncologists and four surgical oncologists were involved. Medical records, tumor registries, and death records were reviewed. RESULTS: Fourteen patients were included; nine were treated for primary presentation and five for recurrent disease. Histologic grade was grade I (n = 3), grade II (n = 3), and grade III (n = 8). Five patients received additional IORT. Radiotherapy complications were generally mild, including nausea (n = 3), diarrhea (n = 1), dehydration (n = 1), anemia (n = 1), and skin changes (n = 1); one required early cessation due to nausea. Thirteen patients had gross negative margins; while 7/13 had negative microscopic margins. Operative complications included anastomotic bleeding (n = 1), fluid collections (n = 2), ileus (n = 3), ascites (n = 2), temporary leg weakness (n = 1), and uncomplicated wound infections (n = 2). In patients with R0 or R1 resections, one and two year local control rates were 64 and 50%. Overall survival for all patients was 90% at 1 year and 74% at 2 years with median survival of 21 months. CONCLUSION: PRT and IORT can be administered effectively in carefully selected patients with resectable RPS. Larger multi-center studies are needed to delineate the role of PRT and IORT to improve local recurrence and survival rates in the treatment of RPS. ( view less ) David W Ollila,Nancy Klauber-DeMore,Leora J Tesche,Cherie M Kuzmiak,Dag Pavic,Lav K Goyal,Jun Lian,Sha Chang,Chad A Livasy,Rachel F Sherron,Carolyn I SartorBACKGROUND: Accelerated partial breast irradiation (APBI) has gained widespread interest as a means of improving the convenience and availability of breast conserving radiotherapy. Intraoperative radiation therapy (IORT) is an APBI technique that delivers breast radiotherapy as a single dose at the... ( view more ) time of partial mastectomy. We adapted the technique of Veronesi to deliver IORT prior to tumor excision to improve delivery to the region at risk and reduce the volume of normal tissue irradiated. METHODS: Patients age >or=55 with ultrasonographically defined tumors ( view less ) Deise Elisabete de Souza,Vasco Senna-Fernandes,Lavínia de Carvalho Brito,Raphael Sancho Sisley de Souza,Daisy França,Cristiano Viana Manoel,Marcela Ceciliano de Almeida,Mario Bernardo-Filho In clinical acupuncture, when acupuncture points are stimulated, several types of reflex responses can be evoked. Consequently, different categories of physiological responses are induced, which include changes in the activities of internal organs and tissues. The acupuncture point Sanyinjiao (SP6)... ( view more ) has been used successfully to treat different human gastrointestinal conditions. The aim of this work was to investigate the effects of end-organ response induced by acupuncture point SP6 on the bioavailability of the radiopharmaceutical sodium pertechnetate (Na99mTcO4) in Wistar rats. Healthy rats were allocated into 2 groups, control-CG and treated-TG. TG was bilaterally stimulated at acupuncture point SP6 with stainless steel needles. Ocular plexus administration of Na99mTcO4 (3.7MBq) was carried out 10 min after every needle insertion in all animals. Ten minutes later, the animals were killed, the organs were isolated, the radioactivity was determined in a well gamma counter, and the percentage of injected dose per gram of tissue (%ID/g) was determined for each organ. The %ID/g was significantly altered (p < 0.05) in the small intestine of TG (0.56 +/- 0.09) when compared to CG (0.82 +/- 0.18). These results may suggest that this stimulation might induce physiological responses capable of altering the bioavailability of the radiopharmaceutical sodium pertechnetate. These findings aid in providing a better understanding of acupuncture and its effects on various organs and tissues. ( view less ) Agnés Poirier,Christoph Funk,Thierry Lavé,Johannes Noé Pharmacokinetic drug-drug interactions (DDIs) are a major concern in drug development. Drug transport, along with drug metabolism via cytochrome P450s (CYPs), is increasingly being considered as an integral part of the overall pharnmacokinetics profile of a drug. Inhibition of transporters can lead... ( view more ) to altered pharmacokinetics, potentially interfering with drug safety and efficacy. There is an increasing number of DDIs observed with statins, which are widely used in combination therapies, and this can be partly attributed to inhibition of individual hepatic transporters. Studies of these inhibitory interactions in vitro has indicated the importance of both hepatic solute carriers of the organic anion transporting polypeptide (OATP) superfamily and CYP inhibition. Mathematical models have been developed to gain more quantitative insights into the interplay between transport and metabolism of drugs. This article reviews new developments in the area of in vitro tools and modeling approaches that are used to study DDIs related to OATP transporters, with a focus on the clinical relevance of the transport-mediated DDIs involving statins. ( view less ) José L Lavín,Kristoffer Kiil,Ohiana Resano,David W Ussery,José A Oguiza BACKGROUND: Pseudomonas syringae is a widespread bacterial plant pathogen, and strains of P. syringae may be assigned to different pathovars based on host specificity among different plant species. The genomes of P. syringae pv. syringae (Psy) B728a, pv. tomato (Pto) DC3000 and pv. phaseolicola (Pp... ( view more )h) 1448A have been recently sequenced providing a major resource for comparative genomic analysis. A mechanism commonly found in bacteria for signal transduction is the two-component system (TCS), which typically consists of a sensor histidine kinase (HK) and a response regulator (RR). P. syringae requires a complex array of TCS proteins to cope with diverse plant hosts, host responses, and environmental conditions. RESULTS: Based on the genomic data, pattern searches with Hidden Markov Model (HMM) profiles have been used to identify putative HKs and RRs. The genomes of Psy B728a, Pto DC3000 and Pph 1448A were found to contain a large number of genes encoding TCS proteins, and a core of complete TCS proteins were shared between these genomes: 30 putative TCS clusters, 11 orphan HKs, 33 orphan RRs, and 16 hybrid HKs. A close analysis of the distribution of genes encoding TCS proteins revealed important differences in TCS proteins among the three P. syringae pathovars. CONCLUSION: In this article we present a thorough analysis of the identification and distribution of TCS proteins among the sequenced genomes of P. syringae. We have identified differences in TCS proteins among the three P. syringae pathovars that may contribute to their diverse host ranges and association with plant hosts. The identification and analysis of the repertoire of TCS proteins in the genomes of P. syringae pathovars constitute a basis for future functional genomic studies of the signal transduction pathways in this important bacterial phytopathogen. ( view less ) Jorge R López-Olvera,Ignasi Marco,Jordi Montané,Encarna Casas-Díaz,Santiago Lavín This study was conducted to assess the stress response of Southern chamois (Rupicapra pyrenaica) to capture and physical restraint and the effects of acepromazine (a short-acting neuroleptic) on this response. Forty free-ranging Southern chamois were captured, injected intramuscularly with aceproma... ( view more )zine (19 animals, randomly selected) or saline (the other 21 animals), and physically restrained for 3 h. Heart rate and body temperature were monitored with telemetric devices, and blood samples were obtained at capture and every hour thereafter to determine hematologic and serum biochemical parameters. The lower heart-rate variability, temperature, erythrocyte count, hemoglobin concentration, packed cell volume (PCV), and serum creatine kinase activity in the animals treated with acepromazine indicated that this agent reduced the adverse effects of stress. According to the differences in heart rate, erythrocyte count, hemoglobin concentration, PCV, lymphocyte count, and serum concentrations of glucose, creatinine, chloride, and potassium, alpha-adrenergic stimulation by catecholamines seemed to be stronger in females, whereas the adrenal-cortex reaction seemed to be stronger in males. The differences in erythrocyte parameters, temperature, serum creatine kinase activity, and serum concentrations of potassium and chloride indicated that acepromazine's beneficial effects were greater in females. ( view less ) I Marco,J R Lopez-Olvera,P Gibert,L Abarca,D Gauthier,S Lavín Two free-ranging southern chamois (Rupicapra pyrenaica) - one 4-year-old male and one 3-year-old male - were diagnosed with clinical dermatophytosis in the French and Spanish Eastern Pyrenees respectively. Skin samples were collected for microbiological studies, Trichophyton mentagrophytes being is... ( view more )olated and identified in both animals. The first chamois was found dead at the base of a cliff, and presented with alopecia and scaling on the dorsum and left forelimb. The second chamois showed grey-yellow, rough to raised scaling and crusting skin lesions at the base of the horns, around the eyes, dorsum of the nose, sternum, tail and limbs. Histological examination was carried out only on the second animal. The main lesions were orthokeratotic hyperkeratosis with focal parakeratosis, irregular to papillary epidermal hyperplasia, intracorneal neutrophilic pustules, perivascular to diffuse dermatitis with neutrophilic folliculitis and furunculosis. In those follicles with folliculitis and/or furunculosis, fungal hyphae and arthrospores associated with the follicular keratin and hair shafts were seen. ( view less )
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