Natriuretic Peptides and Long-Term Mortality in Patients with Severe Aortic Stenosis

Background and aim of the study: The natriuretic peptides, brain natriuretic peptide (BNP) and its N-terminal prohormone (NT-proBNP), can be used as diagnostic and prognostic markers for aortic stenosis (AS). However, the association between BNP, NT-proBNP, and long-term clinical outcomes in patients with severe AS remains uncertain. Methods: A total of 64 patients with severe AS was prospectively enrolled into the study, and underwent clinical and echocardiographic assessments at baseline. Blood samples were drawn for plasma BNP and NT-proBNP analyses. The primary outcome was death from any cause, through a six-year follow up period. Cox proportional hazards modeling was used to examine the association between natriuretic peptides and long-term mortality, adjusting for important clinical factors. Results: During a mean period of 1,520 681 days, 51 patients (80%) were submitted to aortic valve replacement, and 13 patients (20%) were medically managed without surgical interventions. Mortality rates were 13.7% in the surgical group and 62% in the medically managed group (p <0.001). Patients with higher plasma BNP (>135 pg/ml) and NT-proBNP (>1,150 pg/ml) levels at baseline had a greater risk of long-term mortality (hazard ratio [HR] 3.2, 95% confidence interval [CI] 1.1-9.1; HR 4.3, 95% CI 1.4-13.5, respectively). After adjusting for important covariates, both BNP and NT-proBNP remained independently associated with long-term mortality (HR 2.9, 95%CI 1.5-5.7; HR 1.8, 95%CI 1.1-3.1, respectively). Conclusion: In patients with severe AS, plasma BNP and NT-proBNP levels were associated with long-term mortality. The use of these biomarkers to guide treatment might represent an interesting approach that deserves further evaluation. The Journal of Heart Valve Disease 2012;21:331-336

ENVIRONMENTAL TOBACCO SMOKE INDUCES OXIDATIVE STRESS IN DISTINCT BRAIN REGIONS OF INFANT MICE

Environmental tobacco smoke (ETS) leads to the death of 600,000 nonsmokers annually and is associated with disturbances in antioxidant enzyme capacity in the adult rodent brain. However, little is known regarding the influence of ETS on brain development. The aim of this study was to determine levels of malonaldehyde (MDA) and 3-nitrotyrosine (3-NT), as well as enzymatic antioxidant activities of glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), and superoxide dismutase (SOD), in distinct brain structures. BALB/c mice were exposed to ETS twice daily for 1 h from postnatal day 5 through postnatal day 18. Acute exposure was performed for 1 h on postnatal day 18. Mice were euthanized either immediately (0) or 3 h after the last exposure. Immediately after an acute exposure there were higher GR and GST activities and MDA levels in the hippocampus, higher GPx and SOD activities in the prefrontal cortex, and higher GST activity and MDA levels in the striatum and cerebellum. Three hours later there was an increase in SOD activity and MDA levels in the hippocampus and a decrease in the activity of all enzymes in the prefrontal cortex. Immediately after final repeated exposure there were elevated levels of GST and GR activity and decreased GPx activity in the hippocampus. Moreover, a rise was found in GPx and GST activities in the prefrontal cortex and increased GST and GPx activity in the striatum and cerebellum, respectively. After 3 h the prefrontal cortex showed elevated GR and GST activities, and the striatum displayed enhanced GST activity. Data showed that enzymatic antioxidant system in the central nervous system responds to ETS differently in different regions of the brain and that a form of adaptation occurs after several days of exposure.

Liposuction induces a compensatory increase of visceral fat which is effectively counteracted by physical activity: a randomized trial

Context: Liposuction is suggested to result in long-term body fat regain that could lead to increased cardiometabolic risk. We hypothesized that physical activity could prevent this effect. Objective: Our objective was to investigate the effects of liposuction on body fat distribution and cardiometabolic risk factors in women who were either exercise trained or not after surgery. Design, Setting, and Participants: Thirty-six healthy normal-weight women participated in this 6-month randomized controlled trial at the University of Sao Paulo, Sao Paulo, Brazil. Interventions: Patients underwent a small-volume abdominal liposuction. Two months after surgery, the subjects were randomly allocated into two groups: trained (TR, n = 18, 4-month exercise program) and nontrained (NT, n = 18). Main Outcome Measures: Body fat distribution (assessed by computed tomography) was assessed before the intervention (PRE) and 2 months (POST2), and 6 months (POST6) after surgery. Secondary outcome measures included body composition, metabolic parameters and dietary intake, assessed at PRE, POST2, and POST6, and total energy expenditure, physical capacity, and sc adipocyte size and lipid metabolism-related gene expression, assessed at PRE and POST6. Results: Liposuction was effective in reducing sc abdominal fat (PRE vs. POST2, P = 0.0001). Despite the sustained sc abdominal fat decrement at POST6 (P = 0.0001), the NT group showed a significant 10% increase in visceral fat from PRE to POST6 (P = 0.04; effect size = -0.72) and decreased energy expenditure (P = 0.01; effect size = 0.95) when compared with TR. Dietary intake, adipocyte size, and gene expression were unchanged over time. Conclusion: Abdominal liposuction does not induce regrowth of fat, but it does trigger a compensatory increase of visceral fat, which is effectively counteracted by physical activity. (J Clin Endocrinol Metab 97: 2388-2395, 2012)

Selection of Top 10 Quality Indicators for Nutrition Therapy

Background: The identification of useful quality indicators for nutrition therapy (QINTs) is of great interest and a challenge. This study attempted to identify the 10 QINTs that best suit the practice of quality control in nutrition therapy (NT) by evaluating the opinion of experts in NT with the use of psychometric techniques and statistical tools. Methods: Thirty-six QINTs available for clinical application in Brazil were assessed in 2 distinct phases. In phase 1, 26 nutrition experts ranked QINTs by scoring 4 attributes (utility, simplicity, objectivity, low cost) to assess each QINT on a 5-point Likert scale. The top 10 QINTs were identified from the 10 best scores obtained, and the reliability of expert opinion for each indicator was assessed by Cronbach's alpha. In phase 2, experts provided feedback regarding the selected top 10 QINTs by answering 2 closed questions. Results: The top 10 QINTs, in descending order, are the frequency of nutrition screening of hospitalized patients, diarrhea, involuntary withdrawal of enteral feeding tubes, feeding tube obstruction, fasting longer than 24 hours, glycemic dysfunction, estimated energy expenditure and protein needs, central venous catheter infection, compliance of NT indication, and frequency of application of subjective global assessment. Opinions were consistent among the interviewed experts. During feedback, 96% of experts were satisfied with the top 10 QINTs, and 100% had considered them in accordance with their previous opinion. Conclusion: The top 10 QINTs were identified according to their usefulness in clinical practice by obtaining adequate agreement and representativeness of opinion of nutrition experts. (Nutr Clin Pract. 2012;27:261-267)

Second-trimester soft markers: relation to first-trimester nuchal translucency in unaffected pregnancies

Objective Genetic sonography following first-trimester combined screening appears to increase substantially detection rates for Down syndrome but it relies on the unproved assumption of independence between these tests. In this study we aimed to investigate the relationship between first-trimester nuchal translucency (NT) and a series of second-trimester soft markers and structural defects in unaffected pregnancies. Methods NT measurement in the first trimester was followed by second-trimester scan (18 to 23 + 6 weeks) including examination for three categorical markers (intracardiac echogenic foci, hyperechogenic bowel and structural defects) and measurement of nasal bone length, nuchal-fold thickness, femur length, humerus length, renal pelvis diameter and prenasal thickness. All continuous variables were expressed in multiples of the median (MoM) for gestation and correlation coefficients between log-transformed NT and second-trimester variables were calculated. In addition, frequencies of soft markers and structural defects in cases with increased NT were compared to those with normal NT, using MoM cut-offs. Results In a dataset of 1970 cases, NT was significantly correlated (P < 0.05) with all second-trimester continuous variables, the correlation being strongest for nuchal-fold thickness (r = 0.10). There was a higher frequency of cases with second-trimester nuchal-fold thickness above the 97.5th centile (10.7 vs. 2.2%) and hyperechogenic bowel (2.4 vs. 0.1%) in cases with increased NT. Conclusions Straightforward reassessment of risk using likelihood ratios derived from the second-trimester genetic sonogram might lead to inaccurate estimates. Multivariate models using continuous second-trimester variables might be preferable in sequential screening strategies. Copyright. 2012 ISUOG. Published by John Wiley & Sons, Ltd.

Plasma Pro-B-Type Natriuretic Peptide Testing as a Screening Method for Hypertrophic Cardiomyopathy

Background: Clinical multistage risk assessment associated with electrocardiogram (ECG) and NT-proBNP may be a feasible strategy to screen hypertrophic cardiomyopathy (HCM). We investigated the effectiveness of a screening based on ECG and NT-proBNP in first-degree relatives of patients with HCM. Methods and Results: A total of 106 first-degree relatives were included. All individuals were evaluated by echocardiography, ECG, NT-proBNP, and molecular screening (available for 65 individuals). From the 106 individuals, 36 (34%) had diagnosis confirmed by echocardiography. Using echocardiography as the gold standard, ECG criteria had a sensitivity of 0.71, 0.42, and 0.52 for the Romhilt-Estes, Sokolow-Lyon, and Cornell criteria, respectively. Mean values of NT-ProBNP were higher in affected as compared with nonaffected relatives (26.1 vs. 1290.5, P < .001). The AUC of NT-proBNP was 0.98. Using a cutoff value of 70 pg/mL, we observed a sensitivity of 0.92 and specificity of 0.96. Using molecular genetics as the gold standard, ECG criteria had a sensitivity of 0.67, 0.37, and 0.42 for the Romhilt-Estes, Sokolow-Lyon, and Cornell criteria, respectively. Using a cutoff value of 70 pg/mL, we observed a sensitivity of 0.83 and specificity of 0.98. Conclusion: Values of NT-proBNP above 70 pg/mL can be used to effectively select high-risk first-degree relatives for HCM screening. (J Cardiac Fail 2012;18:564-568)

Avian coronavirus Spike Glycoprotein Ectodomain Shows a Low Codon Adaptation to Gallus gallus with Virus-Exclusive Codons in Strategic Amino Acids Positions

This is a study on the Avian coronavirus IBV and chicken host-relationship from the codon usage point of view based on fifty-nine non-redundant IBV S1 sequences (nt 1-507) from strains detected worldwide and chicken tissue-specific protein genes sequences from IBV-replicating sites. The effective number of codons (ENC) values ranged from 36 to 47.8, indicating a high-to-moderate codon usage bias. The highest IBV codon adaptation index (CAI) value was 0.7, indicating a distant virus versus host synonymous codons usage. The ENC x GC3 % curve indicates that both mutational pressure and natural selection are the driving forces on codon usage pattern in S1. The low CAI values agree with a low S protein expression and considering that S protein is a determinant for attachment and neutralization, this could be a further mechanism besides mRNA transcription attenuation for a low expression of this protein leading to an immune camouflage.

Investigation of the Goias Alkaline Province, Central Brazil: Application of gravity and magnetic methods

We investigate the strong magnetic and gravity anomalies of the Goias Alkaline Province (GAP), a region of Late Cretaceous alkaline magmatism along the northern border of the Parana Basin, Brazil. The alkaline complexes (eight of which are present in outcrops, two others inferred from magnetic signals) are characterized by a series of small intrusions forming almost circular magnetic and gravimetric anomalies varying from -4000 to +6000 nT and from -10 to +40 mGal, respectively. We used the Aneuler method and Analytical Signal Amplitude to obtain depth and geometry for mapped sources from the magnetic anomaly data. These results were used as the reference models in the 3D gravity inversion. The 3D inversion results show that the alkaline intrusions have depths of 10-12 km. The intrusions in the northern GAP follow two alignments and have different sizes. In the anomaly magnetic map, dominant guidelines correlate strongly with the extensional regimes that correlate with the rise of alkaline magmatism. The emplacement of these intrusions marks mechanical discontinuities and zones of weakness in the upper crust. According to the 3D inversion results, those intrusions are located within the upper crust (from the surface to 18 km depth) and have spheres as the preferable geometry. Such spherical shapes are more consistent with magmatic chambers instead of plug intrusions. The Registro do Araguaia anomaly (similar to 15 by 25 km) has a particular magnetic signature that indicates that the top is deeper than 1500 m. North of this circular anomaly are lineaments with structural indices indicating contacts on their edges and dikes/sills in the interiors. Results of 3D inversion of magnetic and gravity data suggest that the Registro do Araguaia is the largest body in the area, reaching 18 km depth and indicating a circular layered structure. (C) 2011 Elsevier Ltd. All rights reserved.

Physical exercise improves cardiac autonomic modulation in hypertensive patients independently of angiotensin-converting enzyme inhibitor treatment

We investigated the influence of angiotensin-converting enzyme inhibitor (ACEi) treatment and physical exercise on arterial pressure (AP) and heart rate variability (HRV) in volunteer patients with hypertension. A total of 54 sedentary volunteers were divided into three groups: normotensive (NT Group), hypertensive (HT Group) and HT volunteers treated with ACEi (ACEi Group). All volunteers underwent an aerobic physical-training protocol for 15 weeks. HRV was investigated using a spectral analysis of a time series of R-R interval (RRi) that was obtained in a supine position and during a tilt test. Physical training promoted a significant reduction in the mean arterial pressure of the HT group (113 +/- 3 vs. 106 +/- 1 mm Hg) and the ACEi group (104 +/- 2 vs. 98 +/- 2 mm Hg). Spectral analysis of RRi in the supine position before physical training demonstrated that the NT and ACEi groups had similar values at low frequency (LF; 0.04-0.15 Hz) and high frequency (HF; 0.15-0.5 Hz) oscillations. The HT group had an increase in LF oscillations in absolute and normalized units and a decrease in HF oscillations in normalized units compared with the other groups. The HT group had the lowest responses to the tilt test during LF oscillations in normalized units. Physical training improved the autonomic modulation of the heart rate in the supine position only in the HT group. Physical training promoted a similar increase in autonomic modulation responses in the tilt test in all groups. Our findings show that aerobic physical training improves cardiac autonomic modulation in HT volunteers independently of ACEi treatment. Hypertension Research (2012) 35, 82-87; doi:10.1038/hr.2011.162; published online 29 September 2011

Epidemiology of vampire bat-transmitted rabies virus in Goiás, central Brazil: re-evaluation based on G-L intergenic region

Abstract Background Vampire bat related rabies harms both livestock industry and public health sector in central Brazil. The geographical distributions of vampire bat-transmitted rabies virus variants are delimited by mountain chains. These findings were elucidated by analyzing a high conserved nucleoprotein gene. This study aims to elucidate the detailed epidemiological characters of vampire bat-transmitted rabies virus by phylogenetic methods based on 619-nt sequence including unconserved G-L intergenic region. Findings The vampire bat-transmitted rabies virus isolates divided into 8 phylogenetic lineages in the previous nucleoprotein gene analysis were divided into 10 phylogenetic lineages with significant bootstrap values. The distributions of most variants were reconfirmed to be delimited by mountain chains. Furthermore, variants in undulating areas have narrow distributions and are apparently separated by mountain ridges. Conclusions This study demonstrates that the 619-nt sequence including G-L intergenic region is more useful for a state-level phylogenetic analysis of rabies virus than the partial nucleoprotein gene, and simultaneously that the distribution of vampire bat-transmitted RABV variants tends to be separated not only by mountain chains but also by mountain ridges, thus suggesting that the diversity of vampire bat-transmitted RABV variants was delimited by geographical undulations.

Molecular epidemiology of livestock rabies viruses isolated in the northeastern Brazilian states of Paraíba and Pernambuco from 2003 - 2009

Background Limited or no epidemiological information has been reported for rabies viruses (RABVs) isolated from livestock in the northeastern Brazilian states of Paraíba (PB) and Pernambuco (PE). The aim of this study was to clarify the molecular epidemiology of RABVs circulating in livestock, especially cattle, in these areas between 2003 and 2009. Findings Phylogenetic analysis based on 890 nt of the nucleoprotein (N) gene revealed that the 52 livestock-derived RABV isolates characterized here belonged to a single lineage. These isolates clustered with a vampire bat-related RABV lineage previously identified in other states in Brazil; within PB and PE, this lineage was divided between the previously characterized main lineage and a novel sub-lineage. Conclusions The occurrences of livestock rabies in PB and PE originated from vampire bat RABVs, and the causative RABV lineage has been circulating in this area of northeastern Brazil for at least 7 years. This distribution pattern may correlate to that of a vampire bat population isolated by geographic barriers.

Exercise training in childhood-onset systemic lupus erythematosus: a controlled randomized trial

Abstract Introduction Exercise training has emerged as a promising therapeutic strategy to counteract physical dysfunction in adult systemic lupus erythematosus. However, no longitudinal studies have evaluated the effects of an exercise training program in childhood-onset systemic lupus erythematosus (C-SLE) patients. The objective was to evaluate the safety and the efficacy of a supervised aerobic training program in improving the cardiorespiratory capacity in C-SLE patients. Methods Nineteen physically inactive C-SLE patients were randomly assigned into two groups: trained (TR, n = 10, supervised moderate-intensity aerobic exercise program) and non-trained (NT, n = 9). Gender-, body mass index (BMI)- and age-matched healthy children were recruited as controls (C, n = 10) for baseline (PRE) measurements only. C-SLE patients were assessed at PRE and after 12 weeks of training (POST). Main measurements included exercise tolerance and cardiorespiratory measurements in response to a maximal exercise (that is, peak VO2, chronotropic reserve (CR), and the heart rate recovery (ΔHRR) (that is, the difference between HR at peak exercise and at both the first (ΔHRR1) and second (ΔHRR2) minutes of recovery after exercise). Results The C-SLE NT patients did not present changes in any of the cardiorespiratory parameters at POST (P > 0.05). In contrast, the exercise training program was effective in promoting significant increases in time-to-exhaustion (P = 0.01; ES = 1.07), peak speed (P = 0.01; ES = 1.08), peak VO2 (P = 0.04; ES = 0.86), CR (P = 0.06; ES = 0.83), and in ΔHRR1 and ΔHRR2 (P = 0.003; ES = 1.29 and P = 0.0008; ES = 1.36, respectively) in the C-SLE TR when compared with the NT group. Moreover, cardiorespiratory parameters were comparable between C-SLE TR patients and C subjects after the exercise training intervention, as evidenced by the ANOVA analysis (P > 0.05, TR vs. C). SLEDAI-2K scores remained stable throughout the study. Conclusion A 3-month aerobic exercise training was safe and capable of ameliorating the cardiorespiratory capacity and the autonomic function in C-SLE patients. Trial registration NCT01515163.

Temporary effect of chiseling on the compaction of a Rhodic Hapludox under no-tillage

Mechanical chiseling has been used to alleviate the effects of compaction in soils under no-tillage (NT). However, its effect on the soil physical properties does not seem to have a defined duration period. The purpose of this study was to evaluate the behavior of the bulk density (BD) and degree of compaction (DC) at different soil depths, after chiseling in no-tillage, for one year. The experiment was performed in Ponta Grossa, Paraná State, Brazil, using an Oxisol (Rhodic Hapludox). Bulk density and DC were previously measured in an area under NT for 16 years, then immediately after chiseling (CHI) in May 2009, six months after chiseling (CHI6M) in October 2009 and one year after chiseling (CHI12M) in May 2010. In the layers 0.0-0.10, 0.10-0.20 and 0.20-0.30 m, there was a significant BD reduction CHI and a marked increase CHI6M. The BD values measured CHI12M were similar to those before tillage. Chiseling reduced the DC in the layers 0.0-0.10 m and 0.10-0.20 m, but returned to the initial values one year later. During the evaluation periods CHI, CHI6M and CHI12M, the BD increased in the layer 0.30-0.40 m, compared with NT. The highest DC values were observed six months after chiseling; nevertheless the structural recovery of the soil was considerable, possibly due to the high degree of soil resilience and the influence of the wetting and drying cycles detected in the study period. The chiseling effects, evaluated by BD and DC, lasted less than one year, i.e., the beneficial short-term effects of chiseling on the reduction of the surface BD increased the risk of compaction in deeper soil layers.

Reposição volêmica com soluções salinas em pancreatite e perfil hepático de proteínas apoptóticas e de choque térmico

OBJETIVO: A falência hepática é uma consequência da inflamação sistêmica após pancreatite aguda. Avaliou-se o efeito da reposição volêmica com soluções salinas fisiológicas ou hipertônica na produção hepática de citocinas e na expressão de proteínas ativadas por choque térmico e proteínas ligadas à apoptose durante a pancreatite aguda. MÉTODOS: Ratos Wistar foram divididos em quatro grupos: C - animais controles não submetidos à lesão e nem ao tratamento; NT - animais submetidos à indução de pancreatite aguda e não tratados; SN - animais submetidos à indução de pancreatite aguda e tratados com solução salina normal (NaCl 0,9%); SH - animais submetidos à pancreatite aguda e tratados com solução salina hipertônica (NaCl 7,5%). A pancreatite aguda foi induzida por infusão retrógrada transduodenal de taurocolato de sódio 2,5% no ducto pancreático. Após 4, 12 e 24 horas da indução da pancreatite aguda, analisaram-se, no fígado, TNF-α, IL-1β, IL-6 e IL-10, caspase-2, caspase-7, APAF-1, AIF, HSP60 e HSP90. RESULTADOS: A caspase-2 diminuiu nos grupos SN e SH (p<0,05 versus C) após 12 horas. APAF-1, AIF e HSP90 permaneceram inalterados. Após 4 horas da indução, a capsase-7 aumentou no grupo NT (p<0,01 versus C), embora se mantendo em níveis basais nos grupos reperfundidos. A HSP60 aumentou em todos os grupos após 4 horas (p<0,001 versus C). No entanto, o grupo SH mostrou menor expressão de HSP60 que o grupo SN (p<0,05). A solução salina hipertônica manteve a produção de citocinas em níveis normais. A reperfusão com volume com solução salina normal ou hipertônica, modulou significativamente a expressão de caspase-7. CONCLUSÃO: A reposição volêmica com solução salina normal ou hipertônica foi efetiva em reduzir a caspase-7. Entretanto, somente a solução salina hipertônica foi capaz de regular a produção de citocinas e a expressão de HSP60 em todos os momentos analisados.

Profilo farmacogenetico di determinanti molecolari dell'attività di cisplatino e gemcitabina in pazienti affetti da tumore polmonare non a piccole cellule

Il carcinoma polmonare rappresenta un problema socio-sanitario di grande rilievo, essendo la prima causa di morte per neoplasia. Il carcinoma polmonare non a piccole cellule (non small cell lung cancer - NSCLC) rappresenta la variante istologica più frequente (80% dei casi di tumore polmonare). Al momento della diagnosi circa il 60-70% dei pazienti presenta una malattia in stadio avanzato o metastatico non essendo suscettibile di trattamento chirurgico. Per questi pazienti il trattamento chemioterapico determina un prolungamento della sopravvivenza e un miglioramento della qualità  della vita rispetto alla sola terapia di supporto, identificandosi come standard terapeutico. L'individuazione del migliore trattamento chemioterapico per questo subset di pazienti rappresenta pertanto una delle principali sfide della ricerca oncologica. I regimi polichemioterapici si possono dividere schematicamente in tre generazioni in relazione all'introduzione nel corso degli anni di nuovi agenti chemioterapici. Con l'avvento dei regimi di terza generazione, il trattamento del NSCLC avanzato sembra aver raggiunto un plateau, mancando infatti chiare dimostrazioni di superiorità  di un regime di ultima generazione rispetto ad un altro. Tra questi l'associazione cisplatino e gemcitabina rappresenta uno dei regimi standard più utilizzati in considerazione del suo favorevole rapporto costo-beneficio. Al fine di migliorare i risultati del trattamento chemioterapico in termini di attività  ed efficacia, una possibilità  consiste nell'individuazione di parametri predittivi che ci consentano di identificare il miglior trattamento per il singolo paziente. Tra i vari parametri predittivi valutabili, un crescente interesse è stato rivolto a quelli di carattere genetico, anche grazie all'avvento di nuove tecniche di biologia molecolare e al sequenziamento del genoma umano che ha dato nuovo impulso a studi di farmacogenetica e farmacogenomica. Sulla base di queste considerazioni, in questa tesi è stato effettuato uno studio mirato a valutare l'espressione di determinanti molecolari coinvolti nel meccanismo di azione di gemcitabina e cisplatino in pazienti affetti dai due tipi istologici principali di NSCLC, adenocarcinomi e carcinomi squamocellulari. Lo studio dei livelli di espressione genica è stata effettuata in tessuti di 69 pazienti affetti da NSCLC arruolati presso l'Istituto Europeo di Oncologia di Milano. In particolare, mediante Real Time PCR è stata valutata l'espressione genica di ERCC1, hENT1, dCK, 5'-NT, CDA, RRM1 e RRM2 in 85 campioni isolati con microdissezione da biopsie provenienti dai tessuti polmonari normali o tumorali o dalle metastasi linfonodali. Le analisi di questi tessuti hanno mostrato differenze significative per i pattern di espressione genica di diversi determinanti molecolari potenzialmente utile nel predire l'efficacia di gemcitabina/cisplatino e per personalizzare i trattamenti in pazienti affetti da cancro. In conclusione, l'evoluzione delle tecniche di biologia molecolare promossa dagli studi di farmacogenetica racchiude in sè notevoli potenzialità  per quanto concerne l'ideazione di nuovi protocolli terapeutici. Identificando le caratteristiche genotipiche e i livelli di espressione geniche di determinanti molecolari implicati nella risposta ai farmaci potremmo infatti predisporre delle mappe di chemiosensibilità-chemioresistenza per ciascun paziente, nell'ottica di approntare di volta in volta le più appropriate terapie antitumorali in base alle caratteristiche genetiche del paziente e della sua patologia neoplastica.