The lung cancer exercise training study: a randomized trial of aerobic training, resistance training, or both in postsurgical lung cancer patients: rationale and design.

BACKGROUND: The Lung Cancer Exercise Training Study (LUNGEVITY) is a randomized trial to investigate the efficacy of different types of exercise training on cardiorespiratory fitness (VO2peak), patient-reported outcomes, and the organ components that govern VO2peak in post-operative non-small cell lung cancer (NSCLC) patients. METHODS/DESIGN: Using a single-center, randomized design, 160 subjects (40 patients/study arm) with histologically confirmed stage I-IIIA NSCLC following curative-intent complete surgical resection at Duke University Medical Center (DUMC) will be potentially eligible for this trial. Following baseline assessments, eligible participants will be randomly assigned to one of four conditions: (1) aerobic training alone, (2) resistance training alone, (3) the combination of aerobic and resistance training, or (4) attention-control (progressive stretching). The ultimate goal for all exercise training groups will be 3 supervised exercise sessions per week an intensity above 70% of the individually determined VO2peak for aerobic training and an intensity between 60 and 80% of one-repetition maximum for resistance training, for 30-45 minutes/session. Progressive stretching will be matched to the exercise groups in terms of program length (i.e., 16 weeks), social interaction (participants will receive one-on-one instruction), and duration (30-45 mins/session). The primary study endpoint is VO2peak. Secondary endpoints include: patient-reported outcomes (PROs) (e.g., quality of life, fatigue, depression, etc.) and organ components of the oxygen cascade (i.e., pulmonary function, cardiac function, skeletal muscle function). All endpoints will be assessed at baseline and postintervention (16 weeks). Substudies will include genetic studies regarding individual responses to an exercise stimulus, theoretical determinants of exercise adherence, examination of the psychological mediators of the exercise - PRO relationship, and exercise-induced changes in gene expression. DISCUSSION: VO2peak is becoming increasingly recognized as an outcome of major importance in NSCLC. LUNGEVITY will identify the optimal form of exercise training for NSCLC survivors as well as provide insight into the physiological mechanisms underlying this effect. Overall, this study will contribute to the establishment of clinical exercise therapy rehabilitation guidelines for patients across the entire NSCLC continuum. TRIAL REGISTRATION: NCT00018255.

Un medio de cultivo exento de nitrógeno combinado para el desarrollo de diferentes especies bacterianas fijadoras de N2

p.15-18

Carbon distribution within the plant and rhizosphere for Lolium perenne subjected to anaerobic soil conditions

Perennial ryegrass was subjected to a range of anaerobic treatments. The distribution of C within the plant was determined by pulse labelling the shoots with ¹⁴C-CO₂. A 5 h anaerobic period before pulse labelling reduced by 2.5-10 times the ¹⁴C remaining in the plants and released into the soil. The distribution of the ¹⁴C within the plant was also affected by anaerobiosis. Short periods of anaerobiosis (5 or 10 h) led to increased root-soil ¹⁴C respiration (monitored for 7 days). A longer period of anaerobiosis (48 h) initially inhibited root-soil ¹⁴C respiration, but when aerobiosis was restored. 57% of the total ¹⁴C fixed by the plant was respired by the roots-soil during the following 7 days compared to 19% for the aerobic control. There was a two-thirds reduction in the percentage C retained by the plants stressed for the 48 h compared to the aerobic control. At harvest, all anaerobic treatments were associated with more ¹⁴C remaining in the soil as a proportion of the total ¹⁴C fixed by the plant compared to the aerobic control. © 1990.

Microtubule-targeting-compound PBOX-15 radiosensitizes cancer cells in vitro

BACKGROUND: We proposed to investigate the radiosensitizing properties of PBOX-15, a novel microtubule-disrupting agent, in a panel of cancer cell lines.

RESULTS: PBOX-15 treatment was associated with significant cell kill and increased radiosensitivity in all three cell lines tested. The number of surviving cells in response to the combined treatment was significantly less than PBOX -15 alone in 22Rv1 cells. In these cells, radiosensitisation correlated with induction of G2/M cell cycle arrest by PBOX-15. The compound sustained its activity and increased HIF-1Α expression under hypoxic conditions. PBOX-15 prevented onset of hypoxia-induced radioresistance in hypoxic prostate cells and reduced the surviving fraction of irradiated hypoxic cells to levels similar to those achieved under aerobic conditions.

METHODS: Clonogenic assays were used to determine sensitivity of a panel of cancer cell lines (22Rv1, A549, U87) to PBOX-15 alone or in combination with a single 2Gy dose fraction. Induction of cell cycle arrest and apoptosis was investigated in 22Rv1 prostate cancer cells. The cytotoxic properties of the compound under hypoxic conditions were correlated with Hypoxia Inducible Factor 1 alpha (HIF-1Α) gene and protein expression levels and its radiosensitisation potential was investigated in hypoxic 22Rv1 using clonogenic assays.

CONCLUSIONS: This preliminary data identifies the potential of PBOX-15 as a novel radiosensitising agent for the management of solid tumours and eradication of hypoxic cells.

Transient stimulation of glucose metabolism by insulin in the 1-day chick embryo.

Effects of insulin upon glucose metabolism were investigated in chick embryos explanted in vitro during the first 30 h of incubation. Insulin stimulated the glucose consumption of the chick gastrula (18 h) and neurula (24 h), but had no effect on the late blastula (0 h:laying) and on the stage of six to eight somites (30 h). The increase in glucose consumption concerned both the embryonic area pellucida (AP) and extraembryonic area opaca (AO). AP responded to a greater extent (50%) and at a lower range of concentrations (0.1-1.0 ng/ml) than AO (30%; 1-100 ng/ml). Insulin had no effect on the oxygen consumption of blastoderms, whereas it stimulated the aerobic lactate production (approximately 70% of the additional glucose consumption was converted to lactate). The nanomolar range of stimulating concentrations suggests that insulin has a specific effect in the chick embryo, and that it could modulate glucose metabolism in ovo as well. The transient sensitivity of the embryo to insulin is discussed in relation to behavior of mesodermal cells.

Variación del estado de portador de Staphylococcus aureus en una población de estudiantes de medicina

Para evaluar en estudiantes de medicina la variación del estado de portador de Staphylococcus aureus y su resistencia antimicrobiana, antes y después de la práctica clínica, se realizó un estudio longitudinal en una cohorte de 159 estudiantes de cuarto y noveno semestre universitario. Se tomaron muestras de las zonas periamigdalianas y/o pared posterior de orofaringe, de las fosas nasales y las manos, se cultivaron en agar sangre de cordero al 5% y se incubaron en aerobiosis a 37°C, durante 48 horas. La identificación de Staphylococcus aureus se realizó según las características macroscópicas y pruebas bioquímicas. La susceptibilidad a los antimicrobianos se evaluó mediante el método de difusión de disco, por la técnica de Kirby-Bauer, siguiendo las normas internacionales del Clinical and Laboratory Standards Institute (CLSI), con los siguientes antimicrobianos: ciprofloxacina, vancomicina, oxacilina, cefalotina,clindamicina y rifampicina. La edad promedio de los alumnos de cuarto semestre fue 19,1±1,2 años y el género femenino fue 2/1 más frecuente que el masculino. Se analizaron la presencia de antecedentes como: infecciones, alergias, estado de fumador, otras patologías no infecciosas, uso de antibióticos en los últimos tres meses y procedimientos quirúrgicos u hospitalizaciones seis meses previos a la toma de las muestras. No hubo relación significativa entre la incidencia del estado de portador y los antecedentes estudiados. Se observó un aumento significativo del 15,1%, con respecto al grupo de estudiantes de cuarto semestre, en el estado de portador de S. aureus en el grupo de estudiantes de noveno semestre, después de haber estado expuestos durante tres años al ambiente hospitalario, (p=0,001 Test exacto de Mc Nemar). De los portadores, el 16,4% presentó la bacteria en manos (p<0,001), el 13,8% en fosas nasales (p=0,0015) y el 3,2% en faringe. Por otra parte,el 35,8% de los portadores presentó persistencia, de los cuales el 25,2% fue en fosas nasales; el 4,4%, en faringe y el 3,8% en manos. En cuanto a la resistencia a los antimicrobianos, el 1,9% de las cepas aisladas de los estudiantes de cuarto semestre presentó resistencia: una a ciprofloxacina y dos a clindamicina (tres estudiantes). Por su parte, el 2,5% de las cepas aisladas de estudiantes de noveno semestre fue resistente: una a cefalotina, ciprofloxacina, oxacilina y clindamicina, una a cefalotina y oxacilina y dos a clindamicina (cuatro estudiantes). En el 1,3% del grupo estudiado se aislaron cepas de Staphylococcus aureus Resistentes a la Meticilina (MRSA, por sus siglas en inglés). Estos resultados no muestran diferencias significativas (p=1.000). 

Morfologia e quantificação da microbiota intestinal do curimbatá (Prochilodus lineatus) e do cascudo cinza (Pterygoplichthys anisitsi) cultivados em cativeiro

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Microbiota associated with chronic osteomyelitis of the jaws

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Susceptibility of strict and facultative anaerobes isolated from endodontic infections to metronidazole and β-lactams

Endodontic infections are mixed aerobic-anaerobic infections and several microbial groups associated to these pathologies are also involved in orofacial infections. The goal of this study was to evaluate the susceptibility of microorganisms isolated from endodontic infections to β-lactams and metronidazole and verify the production of β-lactamases. Clinical specimens were collected from 58 endodontic infections of 52 patients. The microorganisms were isolated in selective and non-selective culture media, under anaerobiosis and aerobiosis, and identified using biochemical methods. In the susceptibility tests, it was used an agar dilution method, and Wilkins-Chalgren agar enriched with blood, hemin and menadione for the anaerobes, while Mueller-Hinton agar was employed for the facultative anaerobes. The production of β-lactamases was evaluated through the biological and chromogenic cephalosporin methods. All tested isolates were sensitive to imipenem and 99.3% to amoxicillin/clavulanate association, while 16.1% showed resistance to amoxicillin and penicillin G, and 4.89% to cefoxitin. Resistance to metronidazole was just found in facultative anaerobes. Production of β-lactamases was detected in 18.2% of the isolates and presented a correlation with resistance to β-lactams.

Influence of local tetracycline on the microbiota of alveolar osteitis in rats

The aim of the present study was to evaluate the effects of local tetracycline on the occurrence of alveolar osteitis in rats, and on the microbiota associated to this infection. Forty Wistar rats were randomly assigned to 4 groups (n=10): I - the rats had the maxillary right incisor extracted and the alveolar wound did not receive any treatment; II - adrenaline and Ringer-PRAS were introduced into the alveolar wound; III - the alveolar wound was irrigated with sterile saline; and IV - the alveolar wound was irrigated with an aqueous solution of tetracycline. Microbial samples from the alveolar wounds were collected 2 days after surgery and inoculated on blood agar (with and without 8 μg/mL of tetracycline) and other selective media, and were incubated in either aerobiosis or anaerobiosis at 37°C, for 2 to 14 days. It was verified that tetracycline reduced the occurrence of alveolar osteitis in the rats and caused significant changes in the microbiota of the surgical sites, decreasing the number of anaerobes and increasing the participation of tetracycline-resistant and multi-resistant microorganisms.

Aerobic fitness evaluation during walking tests identifies the maximal lactate steady state

Objective. The aim of this study was to verify the possibility of lactate minimum (LM) determination during a walking test and the validity of such LM protocol on predicting the maximal lactate steady-state (MLSS) intensity. Design. Eleven healthy subjects (24.2 ± 4.5 yr; 74.3 ± 7.7 kg; 176.9 ± 4.1 cm) performed LM tests on a treadmill, consisting of walking at 5.5 km h -1 and with 20-22% of inclination until voluntary exhaustion to induce metabolic acidosis. After 7 minutes of recovery the participants performed an incremental test starting at 7% incline with increments of 2% at each 3 minutes until exhaustion. A polynomial modeling approach (LMp) and a visual inspection (LMv) were used to identify the LM as the exercise intensity associated to the lowest [bLac] during the test. Participants also underwent to 24 constant intensity tests of 30 minutes to determine the MLSS intensity. Results. There were no differences among LMv (12.6 ± 1.7 %), LMp (13.1 ± 1.5 %), and MLSS (13.6 ± 2.1 %) and the Bland and Altman plots evidenced acceptable agreement between them. Conclusion. It was possible to identify the LM during walking tests with intensity imposed by treadmill inclination, and it seemed to be valid on identifying the exercise intensity associated to the MLSS. Copyright © 2012 Guilherme Morais Puga et al.

Avaliação da microbiota associada a osteomielite crônica dos maxilares através de meio de cultura e PCR

Pós-graduação em Odontologia - FOA

Actividad antimicrobiana de la solución de nanopartícula de plata en cultivo de Enterococcus faecalis

Objective. The objective of this study was to evaluate the antimicrobial activity of the silver nanoparticles solution in enterococcus faecallis cultures (ATCC 29212), compared with various solutions of sodium hypoclorithe (NaOCl). Material and methods. Five Agar Petri plates were inoculated with E. faecallis and each of them was placed a cellulose dish embedded with silver nanoparticles solution, or a solution of sodium hypochlorite evaluated (Viarzon, Cloralex, Clorox). Chlorhexidine digluconate 2% was used as positive control and sterile saline solution was used as negative control. After 24 hours of incubation at 37ºc, under aerobic conditions, the zones of inhibition of bacterial growth were measured and the results subjected to the statistical t test among the experimental groups (= 5%). Results. The Cloralex showed to be the most effective reflected in the extent of inhibition in relation to other substances (p< 0.05), except that the chlorhexidine digluconate 2% (p> 0.05). The solution of silver nanoparticles provided a greater zone of inhibition than the sodium hypochlorite solution (Clorox) and Viarzon (p< 0.05). Clorox and Viarzon didn't provide zones of inhibition and were similar to each other (p> 0.05). Conclusions. The solution of silver nanoparticles presents antimicrobial activity in cultured E. faecallis, even higher than other commercial forms of sodium hypochlorite. Further studies should be carried out to determine its viability as irrigating solution in endodontics (AU)

Carrier und Regulatoren des Tartrat- und C 4-Dicarboxylatstoffwechsels von Escherichia coli

In E. coli dient L-Tartrat als Elektronenakzeptor während des anaeroben Wachstums und wird schließlich zu Succinat umgesetzt. Der sekundäre Carrier TtdT (YgjE) von E. coli ist ein Antiporter, der die Aufnahme von L-Tartrat im elektroneutralen Austausch gegen intrazelluläres Succinat katalysiert. TtdT besitzt eine hohe Substratspezifität und katalysiert den Transport von L-Tartrat und Succinat, nicht aber von meso- und D-Tartrat. Das Gen ttdT (ygjE) bildet mit den Genen ttdA und ttdB, welche für die L-Tartratdehydratase kodieren, ein Operon. Das benachbarte Gen ttdR (ygiP) kodiert für TtdR (YgiP), einen Tartrat-spezifischen Regulator vom LysR-Typ. TtdR reguliert die L-Tartratfermentation direkt durch Induktion des ttdABT-Operons und durch Autoregulation. TtdR stellt damit den Tartrat-spezifischen Regulator dar, der auf die Expression des ttdR ttdABT-Genclusters spezialisiert ist. Dagegen reguliert DcuSR, das Zweikomponentensystem für C4-Dicarboxylate, die L-Tartratfermentation indirekt durch die Regulation der Gene für die Fumaratatmung. YfaV und YeaV sind weitere potentielle Tartrattransporter. YfaV katalysiert vermutlich den Transport von C4-Dicarboxylaten, einschließlich Tartrat, unter aeroben und anaeroben Bedingungen. YeaV wird nur in Anwesenheit von L- und meso-Tartrat und unter aeroben Bedingungen gebildet. Die yeaUVWX-Gene unterliegen der trankriptionellen Regulation durch YeaT, dessen Gen yeaT vor yeaU liegt. YeaT ist wie TtdR ein Tartrat-spezifischer Regulator und besitzt eine signifikante Ähnlichkeit zu TtdR.

Funktion der C 4-Dicarboxylat-Transporter DctA und DcuB als Co-Sensoren von DcuS in Escherichia coli

Escherichia coli kann C4-Dicarboxylate sowohl unter aeroben als auch unter anaeroben Bedingungen zur Energiekonservierung nutzen. Die Synthese der beteiligten Transporter und Enzyme wird auf der Transkriptionsebene durch das Zweikomponentensystem DcuSR reguliert. DcuS ist der Sensor für C4-Dicarboxylate. Der Antwortregulator DcuR wird von DcuS aktiviert und induziert die Expression des C4-Dicarboxylat-Transporters DctA unter aeroben Verhältnissen. Anaerob verstärkt DcuSR die Expression des Fumarat/Succinat-Antiporters DcuB, der Fumarase B und der Fumaratreduktase FrdABCD. DctA und DcuB agieren als Co-Sensoren von DcuS und üben einen negativen Effekt auf die Genexpression von dctA bzw. dcuB aus.rnIn dieser Arbeit wurde die Funktion von DctA und DcuB als Co-Sensoren von DcuS untersucht. Sowohl für DcuB als auch für DctA wurde eine direkte Protein-Protein-Interaktion mit DcuS über ein bakterielles Two-Hybrid System nachgewiesen. DcuS bildete ein Transporter-Sensor-Cluster mit DctA und DcuB. C-terminale Verkürzung und die Mutagenese einzelner Aminosäuren der C-terminalen Helix 8b von DctA führten zu einem Verlust der Interaktion mit DcuS. Mit dieser Interaktion gingen sowohl die regulatorische Funktion als auch die Transportfunktion der Punktmutante DctA-L414A verloren. Ein Verlust der Interaktion wurde ebenfalls zwischen einer konstitutiv aktiven DcuS-Mutante und wildtypischem DctA beobachtet. Ebenso zeigte sich eine partielle Reduktion der Interaktion von DcuS mit DctA, wenn DcuS nach der zweiten Transmembranhelix verkürzt wurde. Die Interaktion zwischen DcuS und DctA wurde durch den Effektor Fumarat modifiziert, ging aber nicht komplett verloren.rnDctA konnte in verschiedenen Plasmidsystemen überproduziert werden und bildete Homotrimere. Die Topologie von DctA wurde mit experimentellen und in silico Methoden aufgeklärt. DctA ähnelt der Struktur und Topologie des Aminosäuretransporters Glt aus Pyrococcus horikoshii. DctA besitzt acht Transmembranhelices mit einem cytosolischen N- und C-Terminus sowie zwei Haarnadelschleifen. Die Substratbindung findet höchstwahrscheinlich in den Haarnadelschleifen statt und der Transport erfolgt nach dem „alternating access“ Modell.rnAußerdem wurde die Funktion des Transporters YfcC untersucht. Das Gen yfcC wurde mit Schlüsselgenen des Acetatstoffwechsels co-transkribiert. In yfcC-Deletionsstämmen zeigte sich ein stammspezifischer Defekt bei Wachstum mit Acetat und Transport von Acetat.