Lower N-Acetyl-Aspartate Levels in Prefrontal Cortices in Pediatric Bipolar Disorder: A (1)H Magnetic Resonance Spectroscopy Study

Objective: The few studies applying single-voxel(1)H spectroscopy in children and adolescents with bipolar disorder (BD) have reported low N-acetyl-aspartate (NAA) levels in the dorsolateral prefrontal cortex (DLPFC), and high myo-inositol / phosphocreatine plus creatine (PCr+Cr) ratios in the anterior cingulate. The aim of this study was to evaluate NAA, glycerophosphocholine plus phosphocholine (GPC+PC) and PCr+Cr in various frontal cortical areas in children and adolescents with BD. We hypothesized that NAA levels within the prefrontal cortex are lower in BD patients than in healthy controls, indicating neurodevelopmental alterations in the former. Method: We studied 43 pediatric patients with DSM-IV BD (19 female, mean age 13.2 +/- 2.9 years) and 38 healthy controls (79 female, mean age 13.9 +/- 2.7 years). We conducted multivoxel in vivo (1)H spectroscopy measurements at 1.5 Tesla using a long echo time of 272 ms to obtain bilateral metabolite levels from the medial prefrontal cortex (MPFC), DLPFC (white and gray matter), cingulate (anterior and posterior), and occipital lobes. We used the nonparametric Mann-Whitney U test to compare neurochemical levels between groups. Results: In pediatric BD patients, NAA and GPC+PC levels in the bilateral MPFC, and PCr+Cr levels in the left MPFC were lower than those seen in the controls. In the left DLPFC white matter, levels of NAA and PCr+Cr were also lower in BD patients than in controls. Conclusions: Lower NAA and PCr+Cr levels in the PFC of children and adolescents with BD may be indicative of abnormal dendritic arborization and neuropil, suggesting neurodevelopmental abnormalities. J. Am. Acad. Child Adolesc. Psychiatry, 2011;50(1):85-94.

Reduced medial prefrontal N-Acetyl-Aspartate levels in pediatric major depressive disorder: A multi-voxel in vivo (1)H spectroscopy study

There is increasing evidence of a reciprocal fronto-limbic network in the pathogenesis of mood disorders. Prior in vivo proton ((1)H) spectroscopy studies provide evidence of abnormal neurochemical levels in the cingulate and dorsolateral prefrontal cortex (DLPFC) of adult subjects with major depressive disorder (MOD). We examined whether similar abnormalities occur in children and adolescents with MDD. We collected two-dimensional multi-voxel in vivo 1H spectroscopy data at 1.5 Tesla to quantify levels of N-acetyl-aspartate (NAA), glycerolphosphocholine plus phosphocholine (GPC + PC), and phosphocreatine plus creatine (PCr + Cr) in the DLPFC, medial prefrontal cortex (MPFC), and anterior cingulate (AC) of children and adolescents aged 8-17 years with MDD (n = 16) compared with healthy control subjects (n = 38). Analysis of covariance with age and gender as covariates was performed. MDD subjects showed significantly lower levels of NAA in the right MPFC and right AC than controls. MDD subjects also had significantly lower levels of GPC + PC in the right AC than control subjects. There were no significant differences in other metabolites in the studied regions. Pediatric patients with MDD exhibit neurochemical alterations in prefrontal cortex regions that are important in the monitoring and regulation of emotional states. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Antidepressant-like effects of N-acetyl-L-cysteine in rats

Oxidative stress disturbances have been reported in depressed patients and in animals submitted to stress. Recent evidence suggests that antidepressants may have antioxidant properties. However, the therapeutic potential of antioxidants as antidepressant drugs has not been systematically investigated. Therefore, this study tested the hypothesis that N-acetyl-L-cysteine (NAC), a cysteine prodrug with powerful antioxidant activity, would possess anti depressant-like properties in the forced swimming test. Male Wistar rats were subjected to 15 min of forced swimming and immediately afterward, 5, and 23 h later received intraperitoneal injections of NAC (5, 15, 50, 150, and 250 mg/kg), imipramine, 0 5 mg/kg) or vehicle. One hour later they were submitted to the 5 min test swimming session, where immobility time was recorded. Independent groups of animals received the same treatments and their exploratory activity was measured in an open arena for 5 min. NAC (at the doses of 15, 50, and 150 mg/kg) and imipramine induced a significant decrease in immobility time without changing exploratory behavior measured in an open arena. These results suggest that antioxidants such as NAC may have antidepressant effects. Behavioural Pharmacology (C) 19:747-750 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Triagem familiar para o gene HBB*S e detecção de novos casos de traço falciforme em Pernambuco

OBJETIVO: Estimar o incremento no número adicional de afetados com base na prevalência de síndromes falciformes em familiares de casos-índice. MÉTODOS: Estudo transversal em familiares de amostra aleatória dos casos-índice identificados por programa de triagem neonatal em Pernambuco, no período de 2001 a 2005. O modelo de triagem familiar ampliado incluiu 463 membros familiares de 21 casos-índice. Os familiares foram categorizados como: núcleo reduzido (NR -pai, mãe e irmãos); de primeiro grau (N1 - avós, tios e primos de primeiro grau); de segundo grau (N2 - filhos dos primos de primeiro grau); ampliado (NA - NR+N1+N2) e ampliado de primeiro grau (NA1 -NR+N1). A confirmação da presença de HBB*S e detecção de hemoglobinas anormais foram realizadas por meio da High Performance Liquid Chromathgraphy. A associação entre a presença de HBB*S e variáveis foi testada pelo cálculo da razão de prevalência e respectivos IC 95% e a diferença entre médias verificadas pelo teste t de Student, ao nível de significância de 5%. RESULTADOS: A anemia falciforme era desconhecida por 81% dos familiares; o gene HBB*S esteve presente em 114 familiares. Observou-se que 53,3% da população estudada estava na faixa considerada reprodutiva e 80% das pessoas portadoras do gene HBB*S já tinham gerado filhos. A freqüência foi maior no núcleo NR (69%), mas também elevada no N1 (22,8%). O NA1 resultou na detecção de 69 portadores adicionais (aumento de 172%). CONCLUSÕES: Os resultados indicam que a triagem familiar para identificação de portadores de síndrome falciforme deve ser estendida para os familiares até o primeiro grau.

Auditory event-related potentials in children with benign epilepsy with centro-temporal spikes

Benign focal epilepsy in childhood with centro-temporal spikes (BECTS) is one of the most common forms of idiopathic epilepsy, with onset from age 3 to 14 years. Although the prognosis for children with BECTS is excellent, some studies have revealed neuropsychological deficits in many domains, including language. Auditory event-related potentials (AERPs) reflect activation of different neuronal populations and are suggested to contribute to the evaluation of auditory discrimination (N1), attention allocation and phonological categorization (N2), and echoic memory (mismatch negativity – MMN). The scarce existing literature about this theme motivated the present study, which aims to investigate and document the existing AERP changes in a group of children with BECTS. AERPs were recorded, during the day, to pure and vocal tones and in a conventional auditory oddball paradigm in five children with BECTS (aged 8–12; mean = 10 years; male = 5) and in six gender and age-matched controls. Results revealed high amplitude of AERPs for the group of children with BECTS with a slight latency delay more pronounced in fronto-central electrodes. Children with BECTS may have abnormal central auditory processing, reflected by electrophysiological measures such as AERPs. In advance, AERPs seem a good tool to detect and reliably reveal cortical excitability in children with typical BECTS.

Acetyl-L-Carnitine Prevents Methamphetamine-Induced Structural Damage on Endothelial Cells via ILK-Related MMP-9 Activity

Methamphetamine (METH) is a potent psychostimulant highly used worldwide. Recent studies evidenced the involvement of METH in the breakdown of the blood-brain-barrier (BBB) integrity leading to compromised function. The involvement of the matrix metalloproteinases (MMPs) in the degradation of the neurovascular matrix components and tight junctions (TJs) is one of the most recent findings in METH-induced toxicity. As BBB dysfunction is a pathological feature of many neurological conditions, unveiling new protective agents in this field is of major relevance. AcetylL-carnitine (ALC) has been described to protect the BBB function in different paradigms, but the mechanisms underling its action remain mostly unknown. Here, the immortalized bEnd.3 cell line was used to evaluate the neuroprotective features of ALC in METH-induced damage. Cells were exposed to ranging concentrations of METH, and the protective effect of ALC 1 mM was assessed 24 h after treatment. F-actin rearrangement, TJ expression and distribution, and MMPs activity were evaluated. Integrin-linked kinase (ILK) knockdown cells were used to assess role of ALC in ILK mediated METHtriggered MMPs’ activity. Our results show that METH led to disruption of the actin filaments concomitant with claudin-5 translocation to the cytoplasm. These events were mediated by MMP-9 activation in association with ILK overexpression. Pretreatment with ALC prevented METH-induced activation of MMP-9, preserving claudin-5 location and the structural arrangement of the actin filaments. The present results support the potential of ALC in preserving BBB integrity, highlighting ILK as a new target for the ALC therapeutic use.

Estudos sôbre a alimentação mineral da mandioca (Manihot utilissima Pohl.)

1. The present work was carried out to study the effects of mineral nutrients in the yield as well as in the composition of cassava roots. The variety "Branca de Sta. Catarina" was grown by the sand culture method, the following treatments being used: N0 P0 K0, N0 P1 Kl, N1 P0 K1, N2 P1 K0, N2 P1 K1, N1 P2 K1, and N1 P1 K2, where the figures 0, 1, and 2 denote the relative proportion of a given element. The nutrients were given as follows: N = 35 grams of ammonium nitrate per pot loaded with 120 pounds of washed sand; P1 = 35 grams of monocalcium phosphate; Kl = 28 grams of sulfate of potash. Besides those fertilizers, each pot received 26 grams of magnesium sulfate and weekly doses of micronutrients as indicated by HOAGLAND and ARNON (1939). To apply the macronutrients the total doses were divided in three parts evenly distributed during the life cycle of cassava. 2. As far yield of roots and foliage are concerned, there are a few points to be considered: 2.1. the most striking effect on yield was verified when P was omitted from the fertilization; this treatment gave the poorest yields of the whole experiment; the need of that element for the phosphorylation of the starchy reserves explains such result; 2.2. phosphorus and nitrogen, under the experimental conditions, showed to be the most important nutrients for cassava; the effect of potassium in the weight of the roots produced was much less marked; it is noteworthy to mention, that in absence of potassium, the roots yield decreased whereas the foliage increased; as potassium is essential for the translocation of carbohydrates it is reasonable to admit that sugars produced in the leaves instead of going down and accumulate as starch in the roots were consumed in the production of more green matter. 3. Chemical analyses of roots revealed the following interesting points: 3.1. the lack of phosphorus brought about the most drastic reduction in the starch content of the roots; while the treatment N1 P1 K1 gave 32 per cent of starch, with NI PO Kl the amount found was 25 per cent; this result can be explained by the requirement of P for the enzymatic synthesis of starch; it has to be mentioned that the decrease in the starch content was associated with the remarkable drop in yield observed when P was omitted from the nutrient medium; 3.2. the double dosis of nitrogen in the treatment N2 P1 K1, gave the highest yields; however the increase in yield did not produce any industrial gain: whereas the treatment N1 P1 K1 gave 32 per cent of starch, by raising the N level to N2, the starch content fell to 24 per cent; now, considering the total amount of starch present in the roots, one can see, that the increase in roots yield did not compensate for the marked decrease in the starch content; that is, the amount of starch obtained with N1 P1 K1 does not differ statistically from the quantity obtained with N2 P1 K1; as far we know facts similar to this had been observed in sugar beets and sugar cane, as a result of the interaction between nitrogen and sugar produced; the biochemical aspect of the problem is very interesting: by raising the amount of assimilable nitrogen, instead of the carbohydrates polymerize to starch, they do combine to the amino groups to give proteinaceous materials; actually, it did happen that the protein content increased from 2.91 to 5.14 per cent.

Estudos preliminares sobre as invertases de cafeeiros atacados por Hemileia vastatrix

No presente trabalho, que o autor considera exploratório, foram estudadas as invertases presentes em folhas de cafeeiros das variedades Geisha (SH1 SH5) e Kent (SH2 SH5), inoculados com as raças III (n1 n5) e XXIV (n2 n4) de Hemileia vastatrix. Devido ao genótipo do material utilizado as reações são opostas, ou seja, o cafeeiro Kent é resistente à raça III e suscetível à raça XXIV e o Geisha o contrário. Em cada par de folhas, uma foi inoculada e outra mantida como controle e a determinação das invertases foi feita aos 6 e 16 dias após a inoculação. Os resultados preliminares obtidos mostraram que, independente da variedade de cafeeiro ou da raça de Hemileia vastatrix, nas combinações suscetíveis não houve alteração das invertases presentes, iguais às de plantas sadias, com o máximo de atividade em pH 4,5. Já nas combinações resistentes no 6.º dia após a inoculação houve o aparecimento de uma "invertase ácida pH 4,0", ausente tanto nas plantas sadias como nas combinações suscetíveis das mesmas variedades. O aparecimento da "invertase ácida pH 4,0" está relacionado com a diminuição do teor de sacarose nas folhas. Quanto ao significado desta "invertase ácida pH 4,0" na patogenese da ferrugem do cafeeiro, o autor aventa 3 hipóteses que poderiam ocorrer isolada ou simultaneamente. 1. A sacarose seria desviada para a formação de defesa, tais como fenóis, fitoalexinas e outras. 2. A sacarose seria desviada para outras partes da planta, num processo fisiológico semelhante ao das folhas em senectude. 3. Haveria um aumento da respiração e metabolismo dos tecidos doentes, com o implícito consumo da energia armazenada.

Efeito do N Combinado, do pH e dos níveis de P, Ca, Al e Mn na solução no crescimento e fixação do N2 pelo feijoeiro (Phaseolus vulgaris L.)

Com a finalidade de verificar a hipótese de trabalho de que fatores adversos do solo podem diminuir a fixação do dinitrogênio, foi conduzida uma série de ensaios em solução nutritiva, com as variedades de feijoeiro Carioca, Rico 23 e Venezuela, nas quais se procuraram simular condições que ocorrem no campo. As principais conclusões foram as seguintes: (1) o crescimento foi promovido pelo aumento no nível de N combinado; somente as doses de arranque (de 0,3 a 1,3 milimoles/l), entretanto, aumentaram a nodulação e a fixação simbíótica; (2) a maior produção de matéria seca foi observada em pH 6,0-7,0, podendo atribuir-se a redução no crescimento em pH 4,0 à baixa fixação do N2; (3) um efeito favorável do nível de Ca foi verificado sobre os parâmetros estudados até o nível de 1,25 milimoles/l; (4) observou-se resposta linear às doses de P; (5) o excesso de Al (5-10 ppm) e de Mn (10-20 ppm) inibiu a nodulação, reduziu o crescimento e a fixação do dínitrogênio; (6) embora as tendências fossem as mesmas, houve diferenças no comportamento das variedades.

Efeito do NPK, via foliar, no conteúdo de nutrientes das folhas do algodoeiro (Gossypium hirsutum L.)

O experimento foi conduzido em vasos, nas condições de casa de vegetação da Escola Superior de Agricultura "Luiz de Queiroz", Estado de São Paulo, Brasil, no período de 1975/76. O objetivo foi verificar a influência de pulverizações foliares com NPK na composição de N, P, K nas folhas velhas e folhas novas do algodoeiro (Gossypium hirsutum L.) cv. IAC-13-1. O delineamento experimental foi inteiramente casualizado em esquema fatorial 2 x 3³, em três repetições; sendo dois números de pulverizações (4 e 8), três macronutrientes (N, P, K) em três dosagens (0, 1,2). Cada parcela foi constituída por um vaso com duas plantas. Os tratamentos utilizados constam da Tabela 1 . Os níveis com seus valores médios de N, P2O5 e K2O utilizados em 4 pulverizações: N0=0,N1=0,44,N2=0,84; P0=0, P1= 0,05, P2=0,09; K0=0,K1=0,33,K2=0,66, em 8 pulverizações, N0=0,N1=0,91,N2=1,87; P0=0,P1=0,10, P2=0,20; K0=0,K1=0,70, K2=1,40 em kg/ha, sendo fontes de nutrientes o NH4N0(3), NaH2P0(4)H(2)0 e KCl para N, P(2)0(5) e K(2)0 respectivamente. Os parâmetros empregados na avaliação dos tratamentos foram: teores de N, P, K em folhas velhas e novas do algodoeiro. Nas condições dos experimentos pode-se tirar as seguintes conclusões: A aplicação do efeito quadrático nos seus teores encontrados nas folhas novas apenas em 8 pulverizações, provocando aumento dos teores de P nas folhas velhas. Os algodoeiros não tratados com N revelaram maior teor de K na matéria seca das folhas velhas. O P causou diminuição dos teores de N nas folhas velhas e novas; aumentou os teores de P nas folhas velhas, quando em presença de N. O K aumentou o P nas folhas velhas e novas, diminuiu, porém, o seu teor nas folhas velhas.

Connections between ∞-Poincaré inequality, quasi-convexity, and N1,∞

"Vegeu el resum a l'inici del document del fitxer adjunt."

Phase I and phase II xenobiotic reactions and metabolism of the food-borne carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in aggregating liver cell cultures.

Aggregating fetal liver cell cultures were tested for their ability to metabolize xenobiotics using ethoxycoumarin-O-deethylase (ECOD), as marker of phase I metabolism, and glutathione S-transferase (GST), as marker for phase II reactions. Significant basal activities, stable over 14 days in culture were measured for both ECOD and GST activities. The prototype cytochrome P450 inducers, 3-methylcholanthrene (3-MC) and phenobarbital (PB), increased ECOD and GST activities reaching an optimum 7 days after culturing, followed by a decline in activity. This decline was partially prevented by 1% dimethyl sulfoxide (DMSO) added chronically to the culture medium. DMSO was also found to induce ECOD activity and to a lesser extent GST activity. Furthermore, it potentiated in a dose-dependent manner the induction of ECOD by PB. The food-borne carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is metabolically transformed through a number of pathways in vivo. It was therefore used to examine the metabolic capacity in fetal and adult liver cell aggregates. Metabolism of MeIQx was mainly through N2-conjugation, resulting in formation of the N2-glucuronide and sulfamate conjugates for non-induced fetal liver cells. These metabolites were also found in large amounts in non-induced adult liver cells. Low levels of cytochrome P450-mediated ring-hydroxylated metabolites were detected in both non-induced fetal and adult liver cells. After induction with arochlor (PCB) or 3-MC, the major pathway was ring-hydroxylation (cytochrome P450 dependent), followed by conjugation to beta-glucuronic or sulfuric acid. The presence of the glucuronide conjugate of N-hydroxy-MeIQx, a mutagenic metabolite, suggested an induction of P450 CYP1A2. The metabolism of MeIQx by liver cell aggregates is very similar to that observed in vivo and suggests that aggregating liver cell cultures are a useful model for in vitro metabolic studies in toxicology.

Age differences in the EEG N2 and P3 components during an interference task

The age-related increase in interference susceptibility has been well documented and largely attributed to a deficit in inhibition. In the present study, event-related potentials were used to investigate EEG correlates of inhibitory processing in an interference "Arrow" task. A specific interest was addressed to theN2 and P3 components that respectively refers to conflict monitoring and to efficiency of inhibition processes (Anguera et al,. 2011). Younger (N=10, Mage=24.6) and older (N=10, Mage=65.5) participants were invited to perform a task consisting in deciding, as fast and accurately as possible, whether an arrow presented on a computer screen points to the left or the right, irrespective of its position on the screen (left, middle or right). Responses were provided by key-presses using the left and right indexes. Three conditions were considered: congruent (arrow pointing to the same direction as that of the side of the screen on which it appears), incongruent (arrow pointing to the opposite direction), and neutral (arrow presented at the center of the screen). A total of 56 trials per conditions were performed. Behaviorally, the results showed that in the incongruent condition the percent of correct responses significantly decreased in both groups. After adjustment with simple RT (additional control task), the increased RTs obtained in the old group were significantly more pronounced in the incongruent condition. With respect to electrophysiological data, results showed that frontal site (Fz), the N2 amplitude was significantly larger for the younger as compared to the older (- 2.55 56;V vs. -0.62 56;V respectively) whatever the condition. At central site (Cz), the P3 amplitude significantly decreased in the older compared to the younger in the incongruent condition only. Our findings suggest that the increased RTs observed in older participants during the incongruent condition is more specifically linked to late cognitive resources involved in inhibiting prepotent response tendencies rather than associated with earlier stages of treatment dedicated to conflict monitoring.

Comparison of neoadjuvant cisplatin-based chemotherapy versus radiochemotherapy followed by resection for stage III (N2) NSCLC

Résumé : Objectif: Analyse d'un traitement de chimiothérapie à base de cisplatine de type néoadjuvant en comparaison à un traitement de radio-chimiothérapie suivi de la résection chirurgicale chez des patients présentant un carcinome pulmonaire non à petites cellules de stade Ill (N2) prouvé histologiquement par médiastinoscopie. Evaluation de la morbidité postopératoire, du down-staging ganglionnaire, des taux de survie globale et sans récidive ainsi que du site de récidive. Matériel et méthodes : 82 patients ont été inclus dans l'étude entre Janvier 1994 et Juin 2003, parmi eux 36 ont été traités avec une chimiothérapie néoadjuvante à base de cisplatine et doxétacel (groupe l). Les autres 46 patients ont été soumis à une radio-chimiothérapie néoadjuvante avec administration de 44 Gy (groupe II), soit de façon séquentielle (25 cas) soit concomitante (21 cas). Dans tous les cas des métastases à distance ont été exclues par une évaluation préopératoire comprenant une scintigraphie osseuse, un Ct scan thoraco-abdominal, ou un examen PET scan ainsi qu'une IRM cérébrale. La médiastinoscopie effectuée avant le traitement d'induction chez la totalité des patients, de même que la résection chirurgicale de la tumeur pulmonaire et la lymphadenectomie médiastinale ont été effectuées par le même chirurgien. Résultats : La tumeur pulmonaire était de stade Ti à T2 dans respectivement 47% et 28% des patients des groupes (e II, T3 dans 45% et 41% et T4 dans 8% et 31% des cas. Le type de résection effectué (lobectomie, lobectomie en manchon, pneumonectomie) était comparable dans les deux collectifs (p=0.03) Le taux de mortalité postopératoire à 90 jours était de respectivement 3% et 4 "Vo (p=0.6). Une résection complète (RO) a pu être obtenue dans 92% et 94% des cas (p=0.6) avec un downstaging ganglionnaire médiastinal dans 61% et 78% des patients respectivement (p<0.001). Les taux de survie globale à 5 ans et de survie sans récidive à 5 ans s'élevaient à 40% et à 36% respectivement, sans différence significative entre des tumeurs de stade Ti à T3 et T4. Le taux de survie globale n'était pas significativement différent entre les deux modalités de traitement d'induction, toutefois après radio-chimiothérapie on observait une plus longue survie sans récidive (p.0.04). Il n'y avait par ailleurs pas de différence significative, en termes de morbidité post-opératoire, résecabilité, downstaging ganglionnaire, survie globale et sans récidive, entre les patients traités par radio-chimiothérapie séquentielle ou concomitante. Conclusions : En cas de carcinome pulmonaire non à petites cellules de stade III (N2) un traitement d'induction par radio chimiothérapie suivi de la résection chirurgicale est associé avec un meilleur downstaqing médiastinal ainsi qu'une plus longue survie sans récidive en comparaison au traitement d'induction par chimiothérapie seule. Abstract : Objective: Comparison of prospectively treated patients with neoadjuvant cisplatin-based chemotherapy vs radiochemotherapy followed by resection for mediastinoscopically proven stage III NZ non-small cell lung cancer with respect to postoperative morbidity, pathological nodal downstaging, overall and disease-free survival, and site of recurrence. Methods: Eighty-two patients were enrolled between January 1994 to June 2003, 36 had cisplatin and doxetacel-based chemotherapy (group I) and 46 cisplatin-based radiochemotherapy up to 44 Gy (group II), either as sequential (25 patients) or concomitant (21 patients) treatment. All patients had evaluation of absence of distant metastases by bone scintigraphy, thoracoabdominal CT scan or PET scan, and brain MRI, and all underwent pre-induction mediastinoscopy, resection and mediastinal lymph node dissection by the same surgeon. Results: Group I and II comprised T1/2 tumors in 47 and 28%, 13 tumors in 45 and 41%, and 14 tumors in 8 and 31% of the patients, respectively (P=0.03). There was a similar distribution of the extent of resection (lobectomy, sleeve lobectomy, left and right pneumonectomy) in both groups (P=0.9). Group I and II revealed a postoperative 90-d mortality of 3 and 4% (P=0.6), a RO-resection rate of 92 and 94% (P=0.9), and a pathological mediastinal downstaging in 61 and 78% of the patients (P<0.01), respectively. 5y-overall survival and disease-free survival of all patients were 40 and 36%, respectively, without significant difference between T1-3 and T4 tumors. There was no significant difference in overall survival rate in either induction regimens, however, radiochemotherapy was associated with a longer disease-free survival than chemotherapy (P=0.04). There was no significant difference between concurrent vs sequential radiochemotherapy with respect to postoperative morbidity, resectability, pathological nodal downstaging, survival and disease-free survival. Conclusions: Neoadjuvant cisplatin-based radiochemotherapy was associated with a similar postoperative mortality, an increased pathological nodal downstaging and a better disease-free survival as compared to cisplatin doxetacel-based chemotherapy in patients with stage III (N2) NSCLC although a higher number of 14 tumors were admitted to radiochemotherapy.

Binding of amitriptyline to alpha 1-acid glycoprotein and its variants.

Binding studies have been performed between amitriptyline and i) native alpha 1-acid glycoprotein (AAG); ii) its desialylated form; iii) its two variants, S-AAG and F-AAG; and iv) a mixture of S-AAG and F-AAG. Scatchard analysis revealed the presence of two classes of binding sites on AAG. For native AAG, the first class (of high affinity) has an association constant (Ka1) of 1.5 x 10(6) L mol-1 and a number of binding sites per mole of protein (n1) of 0.25, while the second class (of low affinity) has a Ka2 of 3.2 x 10(4) L mol-1 and a n2 of 0.94. Similar data were found for desialylated AAG. S-AAG and F-AAG do not differ in their association constants measured with amitriptyline, but in their number of binding sites per mole of protein (n): S-AAG: n1 = 0.56, n2 = 0.52; F-AAG: n1 = 0.17, n2 = 0.71. These results confirm those of a previous study, in which a higher affinity of S-AAG towards various basic drugs in comparison with F-AAG has been found.