Two New Supramolecular Assemblies Obtained by Reaction Between Saccharin and Long-chain Diamines

The crystal Structures of heptamethylenediammonium bis(saccharinate) monohydrate, [H(3)N-(CH(2))(7)-NH(3)](sac)(2)center dot H(2)O (1) 0 (1) and octamethylenediammonium bis(saccharinate) hemihydrate, [H(3)N-(CH(2))(8)-NH(3)](sac)(2)center dot 0.5H(2)O (2), were determined-by single-crystal X-ray diffraction methods. Compound I crystallizes in the triclinic space group P (1) over bar with 2 molecules per unit cell, and 2 in the monoclinic space group P2(1)/a with Z = 4. The saccharinate moiety is planar in both compounds presenting bonding characteristics comparable to those found in other saccharinate salts. The ionic crystals are further stabilized by an extensive H-bonding network, which links the anions and cations into an infinite three-dimensional Supramolecular assembly. The FTIR spectra of the adducts are briefly discussed in comparison with those of the constituent Molecules.

Perfil da fluência da fala na síndrome de Williams-Beuren: estudo preliminar

TEMA: o padrão de fala fluente atribuído aos indivíduos com a síndrome de Williams-Beuren sustenta-se pela efetividade da alça fonológica. Alguns estudos citaram a ocorrência de disfluências decorrentes de prejuízos léxico-semânticos, entretanto, a quebra de fluência não foi bem especificada quanto ao tipo e freqüência de ocorrência. OBJETIVO: obter o perfil da fluência da fala de indivíduos com a SWB e comparar com um grupo controle pareado por gênero e idade mental semelhante. MÉTODO: foram avaliados 12 sujeitos com síndrome de Williams-Beuren a com idade cronológica entre 6,6 a 23,6 e idade mental de 4,8 a 14,3 anos que foram comparados a outros 12 sujeitos de idade mental semelhante com ausência de dificuldades de linguagem/aprendizagem. Para avaliação da fluência foi utilizado o Teste de Linguagem Infantil - ABFW, na área de fluência, que possibilitou classificar, quantificar e comparar os dois grupos quanto às tipologias e freqüência de rupturas e velocidade de fala. RESULTADOS: o grupo com a síndrome de Williams-Beuren (SWB) apresentou maior porcentagem de descontinuidade de fala e freqüência aumentada para disfluências comuns do tipo hesitação e repetição de palavras quando comparados aos indivíduos com idade mental semelhante e com desenvolvimento típico de fala e linguagem. CONCLUSÃO: O perfil da fluência da fala apresentado pelos indivíduos com a SWB neste estudo mostrou a presença de disfluências que podem ser decorrentes de prejuízo no processamento léxico-semântico e sintático da informação verbal; ressaltando-se, pois a necessidade de investigações mais sistemáticas sobre este tema.

Avaliação da conduta de profilaxia antirrábica indicada para pessoas envolvidas em agravos com cães e gatos no município de Jaboticabal, SP, no período de 2000 a 2006

Objetivando analisar as indicações de profilaxia antirrábica humana no Município de Jaboticabal-SP, foi realizado um estudo retrospectivo descritivo no período de 2000 a 2006, com levantamento de dados registrados nas fichas de investigação de atendimento e cálculo do custo com as vacinas destinadas à profilaxia pós-exposição. Constatou-se que 2.493 pessoas agredidas por animais foram submetidas à profilaxia com uso de vacina, num total de 7.108 doses e um custo de R$ 179.105,14. da totalidade de casos notificados, 2.184 (71,5 %) foram causados por cães e gatos clinicamente sadios no momento da agressão e que assim se mantiveram durante o período de observação, a qual foi feita pela própria vítima ou pelo dono do animal. Considerando este fato e também a situação epidemiológica da raiva no Município, pode-se inferir que essas vítimas poderiam ter sido dispensadas da profilaxia; entretanto, apenas 464 o foram, ou seja, 1.720 pessoas podem ter recebido vacina sem necessidade, ou seja 4.590 doses a um custo de R$ 114.420,81. em comparação com os números de outros municípios do Estado de São Paulo e com a média nacional, constata-se que o número de profilaxias pós-exposição contra raiva é muito alto em Jaboticabal, evidenciando que na conduta não se considerou o estado do agressor e a condição do Município de área controlada para raiva. Recomenda-se conscientização e capacitação permanentes das equipes de saúde pública quanto à epidemiologia da doença e à necessidade de observação adequada do animal agressor. É essencial a integração dos serviços médicos e veterinários no atendimento às vitimas, visando uma melhor avaliação do caso para que a decisão de se instituir ou não a profilaxia pós-exposição seja feita com critério e segurança.

Aggregate shape and tensile strength measurement

Tensile strength (TS) of soil aggregates is an important indicator of soil quality. However, TS varies with aggregate shape. Thus, the objective of this study was to quantify the influence of aggregate shape on TS and propose a shape standardization protocol to increase accuracy in the measurement of TS. The latter was determined on 7,560 aggregates divided into three shapes, (i) irregular shape (IS), (ii) spherical shape (SS), and (iii) flat surface (FS), while preserving the inherent structure of the aggregate. The aggregates with IS had a larger range in the TS (306 kPa) because of the shape variability when compared with SS (238 kPa) and FS (129 kPa). The TS determined in aggregates with FS had smaller coefficient of variation (46%) in comparison with those of IS (70%) and SS (66%), indicating that the aggregate uniformity reduced the influence of shape on the TS. A smaller force (42.12 kPa) was needed to rupture aggregates with FS than IS (58.43 kPa) and SS (56.89 kPa) because of better force distribution in causing the tensile stress. The use of aggregates with the FS enables an accurate assessment of TS in relation to a wide range of management treatments. Copyright © 2013 by Lippincott Williams & Wilkins.

Immunohistochemical, tomographic, and histological study on onlay bone graft remodeling. Part III: allografts

Objective In the last decades aroused the interest for bone tissue bank as an alternative to autogenous grafting, avoiding donor sites morbidity, surgical time, and costs reduction. The purpose of the study was to compare allografts (ALg) with autografts (AUg) using histology, immunochemistry, and tomographic analysis. Material and methods Fifty-six New Zealand White rabbits were submitted to surgical procedures. Twenty animals were donors and 36 were actually submitted to onlay grafting with ALg (experimental group) and AUg (control group) randomly placed bilaterally in the mandible. Six animals of each group were sacrificed at 3, 5, 7, 10, 20, and 60 postoperative days. Immunolabeling was accomplished with osteoprotegerin (OPG); receptor activator of nuclear factor-k ligand (RANKL); alkaline phosphatase (ALP); osteopontin (OPN); vascular endothelial growth factor (VEGF); tartrate-resistant acid phosphatase (TRAP); collagen type I (COL I); and osteocalcin (OC). Density and volume of the grafts was evaluated on tomography obtained at the surgery and sacrifice. Results The ALg and AUg exhibited similar patterns of density and volume throughout the experiments. The intra-group data showed statistical differences at days 7 and 60 in comparison with other time points (P = 0.001), in both groups. A slight graft expansion from fixation until day 20 (P = 0.532) was observed in the AUg group and then resorbed significantly at the day 60 (P = 0.015). ALg volume remained stable until day 7 and decreased at day 10 (P = 0.045). The light microscopy analysis showed more efficient incorporation of AUg onto the recipient bed if compared with the ALg group. The immunohistochemical labeling picked: at days 10 and 20 with OPG in the AUg group and at day 7 with TRAP in the ALg group (P = 0.001 and P = 0.002, respectively). Conclusions ALg and AUg were not differing in patterns of volume and density during entire experiment. Histological data exhibit more efficient AUg incorporation into recipient bed compared with the ALg group. Immunohistochemistry outcomes demonstrated similar pattern for both ALg and AUg groups, except for an increasing resorption activity in the ALg group mediated by TRAP and in the AUg group by higher OPG labeling. However, this latter observation does not seem to influence clinical outcomes.

Homogeneity assessment of a station climate series (1933-2005) in the Metropolitan Area of Sao Paulo: instruments change and urbanization effects

This work assessed homogeneity of the Institute of Astronomy, Geophysics and Atmospheric Sciences (IAG) weather station climate series, using various statistical techniques. The record from this target station is one of the longest in Brazil, having commenced in 1933 with observations of precipitation, and temperatures and other variables later in 1936. Thus, it is one of the few stations in Brazil with enough data for long-term climate variability and climate change studies. There is, however, a possibility that its data may have been contaminated by some artifacts over time. Admittedly, there was an intervention on the observations in 1958, with the replacement of instruments, for which the size of impact has not been yet evaluated. The station transformed in the course of time from rural to urban, and this may also have influenced homogeneity of the observations and makes the station less representative for climate studies over larger spatial scales. Homogeneity of the target station was assessed applying both absolute, or single station tests, and tests relatively to regional climate, in annual scale, regarding daily precipitation, relative humidity, maximum (TMax), minimum (TMin), and wet bulb temperatures. Among these quantities, only precipitation does not exhibit any inhomogeneity. A clear signal of change of instruments in 1958 was detected in the TMax and relative humidity data, the latter certainly because of its strong dependence on temperature. This signal is not very clear in TMin, but it presents non-climatic discontinuities around 1953 and around 1970. A significant homogeneity break is found around 1990 for TMax and wet bulb temperature. The discontinuities detected after 1958 may have been caused by urbanization, as the observed warming trend in the station is considerably greater than that corresponding to regional climate.

Acidentes e violência na infância: evidências do inquérito sobre atendimentos de emergência por causas externas - Brasil, 2009

Compreender as características e a magnitude das causas externas (acidentes e violência) em crianças de 0 a 9 anos de idade torna-se cada vez mais importante em Saúde Pública. O objetivo do presente artigo foi analisar os atendimentos de emergência por causas externas em crianças. Utilizaram-se dados do Sistema de Vigilância de Violências e Acidentes em Serviços Sentinelas de Urgência e Emergência (Inquérito VIVA), realizado em 74 serviços de urgência do Distrito Federal e 23 capitais no ano 2009. Analisaram-se dados de 7.123 crianças: 6.897 (96,7%) vítimas de acidentes e 226 (3,3%) de violência. Em comparação às vítimas de violência, os atendimentos por acidentes foram mais frequentes entre crianças de 2 a 5 anos, de pele branca e ocorridos no domicílio (p < 0,05). Dentre os acidentes, as quedas e queimaduras predominaram no grupo de 0 a 1 ano, enquanto os acidentes de transporte foram mais frequentes no grupo de 6 a 9 anos (p < 0,001). Quanto às violências, atendimentos por negligência e agressão física predominaram, respectivamente, nos grupos extremos de faixa etária, sendo um familiar identificado como agressor (p < 0,001). Informações sobre ocorrência de causas externas em crianças podem apoiar políticas de promoção da saúde, além de orientar profissionais de saúde, educadores e famílias na prevenção destas causas.

Ambulatory blood pressure monitoring in children with obstructive sleep apnea and primary snoring

Objective: To evaluate the systemic blood pressure (BP) during daytime and nighttime in children with sleep breathing disorders (SBD) and compare parameters of BP in children with diagnosis of obstructive sleep apnea syndrome (OSA) to those one with primary snoring (PS). Methods: Children, both genders, aged from 8 to 12 years, with symptoms of SBD realized an overnight polysomnography followed by a 24 h recording of ambulatory BP. Results: All subjects presented with a history of snoring 7 nights per week. Children who have apnea/hipoapnea index >= four or a apnea index >= one presented a mean BP of 93 +/- 7 mmHg and 85 +/- 9 mmHg diurnal and nocturnal respectively whereas children who have a apnea/hipoapnea < four or a apnea index < one presented 90 +/- 7 mmHg and 77 +/- 2 mmHg. Eight children out of fourteen, from OSA group, lost the physiologic nocturnal dipping of the blood pressure. Among OSA children 57% were considered non-dippers. Two (16%) have presented absence of nocturnal dipping among children with primary snoring. The possibility of OSA children loosing physiologic blood pressure dipping was 6.66 higher than the possibilities of patients from PS group. Discussion: Our results indicate that children with sleep apnea syndrome exhibit a higher 24 h blood pressure when compared with those of primary snoring in form of decreased degree of nocturnal dipping and increased levels of diastolic and mean blood pressure, according to previous studies in literature. OSA in children seems to be associated to the development of hypertension or other cardiovascular disease. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Sorption of aspartic and glutamic aminoacids on calcined hydrotalcite

Sorption of aspartic and glutamic aminoacids by regeneration of calcined hydrotalcite is reported. Hydrotalcite was synthesized by coprecipitation and calcined at 773 K. Sorption experiments were performed at 298 K and 310 K, and the results reveal that at low aminoacids equilibrium concentrations, intercalation of hydroxyl anions takes place while at high equilibrium concentrations, the sorption process occur by means re-hydration and aminoacids intercalation of hydrotalcite. The results also suggested that Asp and Glu sorption is a temperature dependent process. The amount of sorbed amino acid decreases as the temperature increase. The effect is more pronounced for Glu sorption probably due to its higher hydrophobic character, which makes the sorption more difficult in comparison with sorption of Asp at higher temperature.

Efecto del color del oponente en el desencadenamiento de la agresividad en los machos de Betta splendens

[ES] Los machos de Betta splendens se muestran más agresivos ante la presencia de otros machos de la misma especie y color similar al suyo, en comparación con la agresividad desplegada ante machos de tonalidad distinta

Biochemistry in healthy and neoplastic human tissues: metabolic alteration revealed by HR-MAS nuclear magnetic resonance spectroscopy

This thesis is focused on the metabolomic study of human cancer tissues by ex vivo High Resolution-Magic Angle Spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy. This new technique allows for the acquisition of spectra directly on intact tissues (biopsy or surgery), and it has become very important for integrated metabonomics studies. The objective is to identify metabolites that can be used as markers for the discrimination of the different types of cancer, for the grading, and for the assessment of the evolution of the tumour. Furthermore, an attempt to recognize metabolites, that although involved in the metabolism of tumoral tissues in low concentration, can be important modulators of neoplastic proliferation, was performed. In addition, NMR data was integrated with statistical techniques in order to obtain semi-quantitative information about the metabolite markers. In the case of gliomas, the NMR study was correlated with gene expression of neoplastic tissues. Chapter 1 begins with a general description of a new “omics” study, the metabolomics. The study of metabolism can contribute significantly to biomedical research and, ultimately, to clinical medical practice. This rapidly developing discipline involves the study of the metabolome: the total repertoire of small molecules present in cells, tissues, organs, and biological fluids. Metabolomic approaches are becoming increasingly popular in disease diagnosis and will play an important role on improving our understanding of cancer mechanism. Chapter 2 addresses in more detail the basis of NMR Spectroscopy, presenting the new HR-MAS NMR tool, that is gaining importance in the examination of tumour tissues, and in the assessment of tumour grade. Some advanced chemometric methods were used in an attempt to enhance the interpretation and quantitative information of the HR-MAS NMR data are and presented in chapter 3. Chemometric methods seem to have a high potential in the study of human diseases, as it permits the extraction of new and relevant information from spectroscopic data, allowing a better interpretation of the results. Chapter 4 reports results obtained from HR-MAS NMR analyses performed on different brain tumours: medulloblastoma, meningioms and gliomas. The medulloblastoma study is a case report of primitive neuroectodermal tumor (PNET) localised in the cerebellar region by Magnetic Resonance Imaging (MRI) in a 3-year-old child. In vivo single voxel 1H MRS shows high specificity in detecting the main metabolic alterations in the primitive cerebellar lesion; which consist of very high amounts of the choline-containing compounds and of very low levels of creatine derivatives and N-acetylaspartate. Ex vivo HR-MAS NMR, performed at 9.4 Tesla on the neoplastic specimen collected during surgery, allows the unambiguous identification of several metabolites giving a more in-depth evaluation of the metabolic pattern of the lesion. The ex vivo HR-MAS NMR spectra show higher detail than that obtained in vivo. In addition, the spectroscopic data appear to correlate with some morphological features of the medulloblastoma. The present study shows that ex vivo HR-MAS 1H NMR is able to strongly improve the clinical possibility of in vivo MRS and can be used in conjunction with in vivo spectroscopy for clinical purposes. Three histological subtypes of meningiomas (meningothelial, fibrous and oncocytic) were analysed both by in vivo and ex vivo MRS experiments. The ex vivo HR-MAS investigations are very helpful for the assignment of the in vivo resonances of human meningiomas and for the validation of the quantification procedure of in vivo MR spectra. By using one- and two dimensional experiments, several metabolites in different histological subtypes of meningiomas, were identified. The spectroscopic data confirmed the presence of the typical metabolites of these benign neoplasms and, at the same time, that meningomas with different morphological characteristics have different metabolic profiles, particularly regarding macromolecules and lipids. The profile of total choline metabolites (tCho) and the expression of the Kennedy pathway genes in biopsies of human gliomas were also investigated using HR-MAS NMR, and microfluidic genomic cards. 1H HR-MAS spectra, allowed the resolution and relative quantification by LCModel of the resonances from choline (Cho), phosphorylcholine (PC) and glycerolphorylcholine (GPC), the three main components of the combined tCho peak observed in gliomas by in vivo 1H MRS spectroscopy. All glioma biopsies depicted an increase in tCho as calculated from the addition of Cho, PC and GPC HR-MAS resonances. However, the increase was constantly derived from augmented GPC in low grade NMR gliomas or increased PC content in the high grade gliomas, respectively. This circumstance allowed the unambiguous discrimination of high and low grade gliomas by 1H HR-MAS, which could not be achieved by calculating the tCho/Cr ratio commonly used by in vivo 1H MR spectroscopy. The expression of the genes involved in choline metabolism was investigated in the same biopsies. The present findings offer a convenient procedure to classify accurately glioma grade using 1H HR-MAS, providing in addition the genetic background for the alterations of choline metabolism observed in high and low gliomas grade. Chapter 5 reports the study on human gastrointestinal tract (stomach and colon) neoplasms. The human healthy gastric mucosa, and the characteristics of the biochemical profile of human gastric adenocarcinoma in comparison with that of healthy gastric mucosa were analyzed using ex vivo HR-MAS NMR. Healthy human mucosa is mainly characterized by the presence of small metabolites (more than 50 identified) and macromolecules. The adenocarcinoma spectra were dominated by the presence of signals due to triglycerides, that are usually very low in healthy gastric mucosa. The use of spin-echo experiments enable us to detect some metabolites in the unhealthy tissues and to determine their variation with respect to the healthy ones. Then, the ex vivo HR-MAS NMR analysis was applied to human gastric tissue, to obtain information on the molecular steps involved in the gastric carcinogenesis. A microscopic investigation was also carried out in order to identify and locate the lipids in the cellular and extra-cellular environments. Correlation of the morphological changes detected by transmission (TEM) and scanning (SEM) electron microscopy, with the metabolic profile of gastric mucosa in healthy, gastric atrophy autoimmune diseases (AAG), Helicobacter pylori-related gastritis and adenocarcinoma subjects, were obtained. These ultrastructural studies of AAG and gastric adenocarcinoma revealed lipid intra- and extra-cellularly accumulation associated with a severe prenecrotic hypoxia and mitochondrial degeneration. A deep insight into the metabolic profile of human healthy and neoplastic colon tissues was gained using ex vivo HR-MAS NMR spectroscopy in combination with multivariate methods: Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA). The NMR spectra of healthy tissues highlight different metabolic profiles with respect to those of neoplastic and microscopically normal colon specimens (these last obtained at least 15 cm far from the adenocarcinoma). Furthermore, metabolic variations are detected not only for neoplastic tissues with different histological diagnosis, but also for those classified identical by histological analysis. These findings suggest that the same subclass of colon carcinoma is characterized, at a certain degree, by metabolic heterogeneity. The statistical multivariate approach applied to the NMR data is crucial in order to find metabolic markers of the neoplastic state of colon tissues, and to correctly classify the samples. Significant different levels of choline containing compounds, taurine and myoinositol, were observed. Chapter 6 deals with the metabolic profile of normal and tumoral renal human tissues obtained by ex vivo HR-MAS NMR. The spectra of human normal cortex and medulla show the presence of differently distributed osmolytes as markers of physiological renal condition. The marked decrease or disappearance of these metabolites and the high lipid content (triglycerides and cholesteryl esters) is typical of clear cell renal carcinoma (RCC), while papillary RCC is characterized by the absence of lipids and very high amounts of taurine. This research is a contribution to the biochemical classification of renal neoplastic pathologies, especially for RCCs, which can be evaluated by in vivo MRS for clinical purposes. Moreover, these data help to gain a better knowledge of the molecular processes envolved in the onset of renal carcinogenesis.

Modeling and simulation of a synthetic genetic circuit that implements a multicelled behavior in a growing microcolony of E. coli

Synthetic Biology is a relatively new discipline, born at the beginning of the New Millennium, that brings the typical engineering approach (abstraction, modularity and standardization) to biotechnology. These principles aim to tame the extreme complexity of the various components and aid the construction of artificial biological systems with specific functions, usually by means of synthetic genetic circuits implemented in bacteria or simple eukaryotes like yeast. The cell becomes a programmable machine and its low-level programming language is made of strings of DNA. This work was performed in collaboration with researchers of the Department of Electrical Engineering of the University of Washington in Seattle and also with a student of the Corso di Laurea Magistrale in Ingegneria Biomedica at the University of Bologna: Marilisa Cortesi. During the collaboration I contributed to a Synthetic Biology project already started in the Klavins Laboratory. In particular, I modeled and subsequently simulated a synthetic genetic circuit that was ideated for the implementation of a multicelled behavior in a growing bacterial microcolony. In the first chapter the foundations of molecular biology are introduced: structure of the nucleic acids, transcription, translation and methods to regulate gene expression. An introduction to Synthetic Biology completes the section. In the second chapter is described the synthetic genetic circuit that was conceived to make spontaneously emerge, from an isogenic microcolony of bacteria, two different groups of cells, termed leaders and followers. The circuit exploits the intrinsic stochasticity of gene expression and intercellular communication via small molecules to break the symmetry in the phenotype of the microcolony. The four modules of the circuit (coin flipper, sender, receiver and follower) and their interactions are then illustrated. In the third chapter is derived the mathematical representation of the various components of the circuit and the several simplifying assumptions are made explicit. Transcription and translation are modeled as a single step and gene expression is function of the intracellular concentration of the various transcription factors that act on the different promoters of the circuit. A list of the various parameters and a justification for their value closes the chapter. In the fourth chapter are described the main characteristics of the gro simulation environment, developed by the Self Organizing Systems Laboratory of the University of Washington. Then, a sensitivity analysis performed to pinpoint the desirable characteristics of the various genetic components is detailed. The sensitivity analysis makes use of a cost function that is based on the fraction of cells in each one of the different possible states at the end of the simulation and the wanted outcome. Thanks to a particular kind of scatter plot, the parameters are ranked. Starting from an initial condition in which all the parameters assume their nominal value, the ranking suggest which parameter to tune in order to reach the goal. Obtaining a microcolony in which almost all the cells are in the follower state and only a few in the leader state seems to be the most difficult task. A small number of leader cells struggle to produce enough signal to turn the rest of the microcolony in the follower state. It is possible to obtain a microcolony in which the majority of cells are followers by increasing as much as possible the production of signal. Reaching the goal of a microcolony that is split in half between leaders and followers is comparatively easy. The best strategy seems to be increasing slightly the production of the enzyme. To end up with a majority of leaders, instead, it is advisable to increase the basal expression of the coin flipper module. At the end of the chapter, a possible future application of the leader election circuit, the spontaneous formation of spatial patterns in a microcolony, is modeled with the finite state machine formalism. The gro simulations provide insights into the genetic components that are needed to implement the behavior. In particular, since both the examples of pattern formation rely on a local version of Leader Election, a short-range communication system is essential. Moreover, new synthetic components that allow to reliably downregulate the growth rate in specific cells without side effects need to be developed. In the appendix are listed the gro code utilized to simulate the model of the circuit, a script in the Python programming language that was used to split the simulations on a Linux cluster and the Matlab code developed to analyze the data.

Design, synthesis and biological evaluation of substituted naphthalene diimides as anticancer agents

It has been proved that naphthalene diimide (NDI) derivatives display anticancer properties as intercalators and G-quadruplex-binding ligands, leading to DNA damage, senescence and down-regulation of oncogene expression. This thesis deals with the design and synthesis of disubstituted and tetrasubstituted NDI derivatives endowed with anticancer activity, interacting with DNA together with other targets implicated in cancer development. Disubstituted NDI compounds have been designed with the aim to provide potential multitarget directed ligands (MTDLs), in order to create molecules able to simultaneously interact with some of the different targets involved in this pathology. The most active compound, displayed antiproliferative activity in submicromolar range, especially against colon and prostate cancer cell lines, the ability to bind duplex and quadruplex DNA, to inhibit Taq polymerase and telomerase, to trigger caspase activation by a possible oxidative mechanism, to downregulate ERK 2 protein and to inhibit ERKs phosphorylation, without acting directly on microtubules and tubuline. Tetrasubstituted NDI compounds have been designed as G-quadruplex-binding ligands endowed with anticancer activity. In order to improve the cellular uptake of the lead compound, the N-methylpiperazine moiety have been replaced with different aromatic systems and methoxypropyl groups. The most interesting compound was 1d, which was able to interact with the G-quadruplexes both telomeric and in HSP90 promoter region, and it has been co-crystallized with the human telomeric G-quadruplex, to directly verify its ability to bind this kind of structure, and also to investigate its binding mode. All the morpholino substituted compounds show antiproliferative activity in submicromolar values mainly in pancreatic and lung cancer cell lines, and they show an improved biological profile in comparison with that of the lead compound. In conclusion, both these studies, may represent a promising starting point for the development of new interesting molecules useful for the treatment of cancer, underlining the versatility of the NDI scaffold.

Glucocorticoid Replacement and Mortality in Patients with Nonfunctioning Pituitary Adenoma

Current treatment guidelines generally suggest using lower and weight-adjusted glucocorticoid replacement doses in patients with insufficiency of the hypothalamic-pituitary-adrenal (HPA) axis. Although data in patients with acromegaly revealed a positive association between glucocorticoid dose and mortality, no comparable results exist in patients with nonfunctioning pituitary adenomas (NFPA).

Sweat test in patients with glucose-6-phosphate-1-dehydrogenase deficiency

BACKGROUND: A false-positive sweat test in patients with deficiency of glucose-6-phosphate-1-dehydrogenase (EC 1.1.1.49; G6PD) is repeatedly reported. METHODS: Sweat chloride or conductivity was measured in 11 patients with G6PD deficiency. RESULTS: Mean (SD) chloride level (n = 8, median age 9.2 years, range 1.9-48.5) was 18.8 (9.6 mmol/l) and, mean (SD) sodium level was 26.0 (10.0 mmol/l), respectively, and mean (SD) conductivity (n = 3, median age 6.6 years, range 1.9-40.5) was 34.3 (6.5 mmol/l). CONCLUSION: In sweat of 11 patients with G6PD deficiency we did not find any abnormality. The reason for alleged false-positive sweat test in patients with G6PD deficiency is not known and we were unable to identify any original reference. It appears that tables of putative false-positive sweat tests in several disease states have been directly "copied and pasted" from one paper or textbook to another without verifying the original literature, a phenomenon one can call "chain citation".