Ex vivo UV-vis and FTIR photoacoustic spectroscopy of natural nanoemulsions from cellulose nanocrystals and saponins topically applied into the skin: Diffusion rates and physicochemical evaluation.

Nanoemulsions are increasingly gaining importance in the development of topically applied medicine and cosmetic products because their small droplets favor the penetration rates of active compounds into the body. In this scenario, the measurements of their diffusion rates as well as eventual physicochemical changes in the target tissues are of utmost importance. It is also recognized that the use of natural surfactants can avoid allergic reactions as frequently observed for synthetic products. The natural saponins extracted from Sapindus Saponaria have the property of forming foam and are exploited as biocompatible and biodegradable, while cellulose nanocrystals are known to increase the stability of a formulation avoiding the coalescence of drops at the interface. Therefore, nanoemulsions combining natural saponins and cellulose nanocrystals are promising systems that may facilitate greater diffusion rates of molecules into the skin, being candidates to substitute synthetic formulations. This study applied the Photoacoustic Spectroscopy technique to measure the diffusion rates and the physicochemical properties of nanoemulsified formulations containing saponins and cellulose nanocrystals topically applied to the skin. The ex vivo study combined the first-time photoacoustic measurements performed in both ultraviolet-visible and mid-infrared spectral regions. The toxicity of these formulations in L929 cells was also evaluated. The results showed that the formulations were able to propagate throughout the skin to a depth of approximately 756 µm, reaching the dermal side. The non-observation of absorbing band shifting or new bands in the FTIR spectra suggests that there were no structural changes in the skin as well as in the formulations after the nanoemulsions administration. The cytotoxicity results showed that the increase of cellulose nanocrystals concentration decreased cellular toxicity. In conclusion, the results demonstrated the advantage of combining photoacoustic methods in the ultraviolet-visible and mid-infrared spectral regions to analyze drug diffusion and interaction with the skin tissues. Both methods complement each other, allowing the confirmation of the nanoemulsion diffusion through the skin and also suggesting there were no detectable physicochemical changes in the tissues. Formulations stabilized with saponins and cellulose nanocrystals showed great potential for the development of topically administered cosmetics and drugs.

Genomic and transcriptomic characterization of the human glioblastoma cell line AHOL1.

Cancer cell lines are widely used as in vitro models of tumorigenesis, facilitating fundamental discoveries in cancer biology and translational medicine. Currently, there are few options for glioblastoma (GBM) treatment and limited in vitro models with accurate genomic and transcriptomic characterization. Here, a detailed characterization of a new GBM cell line, namely AHOL1, was conducted in order to fully characterize its molecular composition based on its karyotype, copy number alteration (CNA), and transcriptome profiling, followed by the validation of key elements associated with GBM tumorigenesis. Large numbers of CNAs and differentially expressed genes (DEGs) were identified. CNAs were distributed throughout the genome, including gains at Xq11.1-q28, Xp22.33-p11.1, Xq21.1-q21.33, 4p15.1-p14, 8q23.2-q23.3 and losses at Yq11.21-q12, Yp11.31-p11.2, and 15q11.1-q11.2 positions. Nine druggable genes were identified, including HCRTR2, ETV1, PTPRD, PRKX, STS, RPS6KA6, ZFY, USP9Y, and KDM5D. By integrating DEGs and CNAs, we identified 57 overlapping genes enriched in fourteen pathways. Altered expression of several cancer-related candidates found in the DEGs-CNA dataset was confirmed by RT-qPCR. Taken together, this first comprehensive genomic and transcriptomic landscape of AHOL1 provides unique resources for further studies and identifies several druggable targets that may be useful for therapeutics and biologic and molecular investigation of GBM.

Genomic and transcriptomic characterization of the human glioblastoma cell line AHOL1

Cancer cell lines are widely used as in vitro models of tumorigenesis, facilitating fundamental discoveries in cancer biology and translational medicine. Currently, there are few options for glioblastoma (GBM) treatment and limited in vitro models with accurate genomic and transcriptomic characterization. Here, a detailed characterization of a new GBM cell line, namely AHOL1, was conducted in order to fully characterize its molecular composition based on its karyotype, copy number alteration (CNA), and transcriptome profiling, followed by the validation of key elements associated with GBM tumorigenesis. Large numbers of CNAs and differentially expressed genes (DEGs) were identified. CNAs were distributed throughout the genome, including gains at Xq11.1-q28, Xp22.33-p11.1, Xq21.1-q21.33, 4p15.1-p14, 8q23.2-q23.3 and losses at Yq11.21-q12, Yp11.31-p11.2, and 15q11.1-q11.2 positions. Nine druggable genes were identified, including HCRTR2, ETV1, PTPRD, PRKX, STS, RPS6KA6, ZFY, USP9Y, and KDM5D. By integrating DEGs and CNAs, we identified 57 overlapping genes enriched in fourteen pathways. Altered expression of several cancer-related candidates found in the DEGs-CNA dataset was confirmed by RT-qPCR. Taken together, this first comprehensive genomic and transcriptomic landscape of AHOL1 provides unique resources for further studies and identifies several druggable targets that may be useful for therapeutics and biologic and molecular investigation of GBM.

[Reflections on Three Episodes of Louis Pasteur's Life as Seen in the William Dieterle's Movie (1936)]. / Réflexions sur trois épisodes de la vie de Louis Pasteur vus au travers du film de William Dieterle (1936).

Despite the criticism and reservations made about him still nowadays, Louis Pasteur may be considered one of the most important scientists of the last two centuries in public health, even if the work of the numerous scientists who preceded him have largely contributed to the successes he obtained without following too much to the rules of deontology and ethics currently in force in the world of research and medicine. He has definitively put down, by his experiments, the "theory of spontaneous generation" in force since antiquity, validated that of "germs or microbes", enacted the first rules of asepsis, while inspiring those of the antisepsis applied by Joseph Lister, and developed a certain number of vaccinations in veterinary and human medicine, including the anti-rabies, the one which made him famous all over the world. All this was not done without difficulty and Pasteur encountered for a large part of his life the misunderstanding of his contemporaries and the hostility of the medical world to which he did not belong. The authors comment in this text the movie The Story of Louis Pasteur by William Dieterle, filmed in 1936, based on the knowledge acquired since that date and doing the part of the real and the fiction.

Malgré les critiques et les réserves dont il est l'objet aujourd'hui, Louis Pasteur peut être considéré comme l'un des scientifiques les plus importants de ces deux derniers siècles en matière de santé publique, même si les apports des nombreux hommes de science qui l'ont précédé ont largement contribué aux succès qu'il obtint sans trop se soucier des règles de déontologie et d'éthique actuellement en vigueur dans le monde de la recherche et de la médecine. Il a mis définitivement à bas, par ses expériences, la « théorie de la génération spontanée ¼ en vigueur depuis l'Antiquité, validé celle « des germes ou microbes ¼, édicté les premières règles de l'asepsie tout en inspirant celles de l'antisepsie appliquée par Joseph Lister et mit au point un certain nombre de vaccinations en médecine vétérinaire puis humaine, notamment celle contre la rage, ce qui le rendit célèbre dans le monde entier. Tout cela ne s'est pas fait sans difficulté, et Pasteur s'est heurté pendant une grande partie de sa vie à l'incompréhension de ses contemporains et à l'hostilité du monde médical auquel il n'appartenait pas. Les auteurs commentent dans ce texte le film L'Histoire de Louis Pasteur de William Dieterle, tourné en 1936, en s'appuyant sur les connaissances acquises depuis cette date et en faisant la part du réel et de l'imaginé.

Piper regnellii extract biopolymer-based microparticles: production, characterization and antifungal activity.

AIMS: This study aims to improve characteristics of Piper regnellii extract to make it applicable in formulations to treat dermatophytosis, also known as ringworm. METHODS AND RESULTS: Microparticles (MPs) were produced by spray drying with gelatin, alginate and chitosan as encapsulating agents; characterized by scanning electron microscopy, encapsulation efficiency, thermal analyses and X-ray diffraction; and tested against Trichophyton rubrum by broth microdilution. Produced MPs had a mean diameter less than 2 µm, an increase in stability and release of the extract and good results for encapsulation efficiency, being 85·6% to gelatin MP, 71·3% to chitosan MP and 60·6% to alginate. MPs preserved the antifungal activity of P. regnellii extract T. rubrum. CONCLUSION: Microencapsulation provided a significant improvement in the stability of the P. regnellii extract and better solubilization of chemical compounds, maintaining the antifungal effect against T. rubrum. SIGNIFICANCE AND IMPACT OF THE STUDY: These results are useful for developing a formulation to treat fungal infections caused by dermatophyte species.

Fermi energy dependence of the optical emission in core/shell InAs nanowire homostructures.

InAs nanowires grown by vapor-liquid-solid (VLS) method are investigated by photoluminescence. We observe that the Fermi energy of all samples is reduced by ∼20 meV when the size of the Au nanoparticle used for catalysis is increased from 5 to 20 nm. Additional capping with a thin InP shell enhances the optical emission and does not affect the Fermi energy. The unexpected behavior of the Fermi energy is attributed to the differences in the residual donor (likely carbon) incorporation in the axial (low) and lateral (high incorporation) growth in the VLS and vapor-solid (VS) methods, respectively. The different impurity incorporation rate in these two regions leads to a core/shell InAs homostructure. In this case, the minority carriers (holes) diffuse to the core due to the built-in electric field created by the radial impurity distribution. As a result, the optical emission is dominated by the core region rather than by the more heavily doped InAs shell. Thus, the photoluminescence spectra and the Fermi energy become sensitive to the core diameter. These results are corroborated by a theoretical model using a self-consistent method to calculate the radial carrier distribution and Fermi energy for distinct diameters of Au nanoparticles.

Suicide in patients with genitourinary malignancies.

Genitourinary cancers are significant causes of morbidity and mortality around the world. The present review summarises the current literature on suicide and its risk factors among patients with genitourinary cancers. The review was based on relevant articles published in MEDLINE, ProQuest, PsycINFO, Science Direct and Scopus databases. Patients with prostate cancer represented the most important risk group for suicide, among patients with urogenital cancers. Other risk factors are male gender, older age, white race, advanced disease, living alone and co-existing psychological comorbidities. Findings from the review call for a greater caregiver awareness on psychosocial morbidity and suicidality among genitourinary cancer patients pre- and post-treatment and their early identification, adoption of risk-reduction strategies and prompt referral for expert mental health care.

Revealing the diversity of Cloeodes Traver, 1938 (Ephemeroptera: Baetidae) in the Neotropics: description of eleven new species from Brazilian mountain ranges.

In the present work, based on material from distinct mountain ranges in Brazil, 11 new species of Cloeodes with hind wings or hind wing pads are described, illustrated and discussed. Among the new species, in C. aiuruoca, C. amantykyra, C. atlanticus, C. boldrinii and C. ioachimi, the apex of the fore femora in the nymphs is extremely projected (a characteristic previously found only in two species of the genus). Cloeodes guara and C. tracheatus share the presence of unusual large and dark gills. Cloeodes melanotarsus is readily distinguished by conspicuous blackish tarsi, C. lucifer by the bright yellow coloration of tergum I, and C. xyrognathos by blade-like incisors. Cloeodes magnus, besides being the largest species of the genus, with a body size reaching 12 mm, possess short maxillary palp. Comments on the presence of C. irvingi and C. opacus in Brazil are also provided. An interactive online key is provided for the nymphs of all the species of Cloeodes in which hind wing pads are present.

Surgical treatment of type 2 diabetes in subjects with mild obesity: mechanisms underlying metabolic improvements.

BACKGROUND: This study aims to assess the clinical and physiological effects of Roux-en-Y gastric bypass (RYGBP) on type 2 diabetes associated with mild obesity (body mass index [BMI] 30-34.9 kg/m(2)) over 24 months postsurgery. METHODS: In this prospective trial, 36 mildly obese subjects (19 males) with type 2 diabetes using oral antidiabetic drugs with (n = 24) or without insulin (n = 12) underwent RYGBP. Follow-up was conducted at baseline and 3, 6, 12, and 24 months postsurgery. The following endpoints were considered: changes in HbA1c, fasting glucose and insulin, antidiabetic therapy, BMI, oral glucose insulin sensitivity [OGIS, from meal tolerance test (MTT)], beta-cell secretory function [ΔCP(0-30)/ΔGlu(0-30) (ΔC-peptide/Δglucose ratio, MTT 0-30 min), disposition index (DI = OGIS [Symbol: see text] ΔCP(0-30)/ΔGlu(0-30)], glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) [incremental area under the curve (AUCi)], adiponectin, C-reactive protein, and lipids. RESULTS: All subjects achieved normal-to-overweight BMI after 3 months. Over 24 months, 31/36 (86 %) subjects presented HbA1c <7 % [complete and partial remission of diabetes in 9/36 (22 %) and 1/36 (3 %), respectively]. Since 3 months postsurgery, improvements were observed in OGIS [290 (174) to 373 (77) ml/min/m(2), P = 0.009], ΔCP(0-30)/ΔGlu(0-30) [0.24 (0.19) to 0.52 (0.34) ng/mg, P = 0.001], DI [7.16 (8.53) to 19.8 (15.4) (ng/mg) (ml/min/m(2)), P = 0.001], GLP-1 AUCi [0.56 (0.64) to 3.97 (3.86) ng/dl [Symbol: see text] 10 min [Symbol: see text] 103, P = 0.000], and GIP AUCi [30.2 (12.6) to 27.0 (20.2) ng/dl [Symbol: see text] 10 min [Symbol: see text] 103, P = 0.004]. At baseline and after 12 months, subjects with diabetes nonremission had longer diabetes duration, higher HbA1c, lower beta-cell secretory function, and higher first 30-min GIP AUCi, compared with those with remission. CONCLUSIONS: RYGBP improves the glucose metabolism in subjects with type 2 diabetes and mild obesity. This effect is associated with improvement of insulin sensitivity, beta-cell secretory function, and incretin secretion.

Ecotope effect in Triatoma brasiliensis (Hemiptera: Reduviidae) suggests phenotypic plasticity rather than adaptation.

Triatoma brasiliensis (Hemiptera: Reduviidae) is an important vector of Chagas' disease in both sylvatic and peridomestic ecotopes. Discriminating between these populations of Triatominae has been proposed as a means of investigating re-infestation rates of human dwellings. Geometric morphometrics have been widely applied in the study of Triatominae polymorphisms at species and population levels. This study characterizes morphometric differences between sylvatic and peridomestic populations, as well as between sexes in T. brasiliensis specimens from Jaguaruana, Ceará, in northeastern Brazil. No differences in either the shape or size of the cephalic capsule were apparent between sexes or ecotopes. However, the wings showed differentiation in shape and size. Sexual dimorphism was detected, with females presenting significantly higher values and conformations. Size differentiation was also evident, with sylvatic specimens being generally larger than peridomestic examples. These results indicate that differences in the wings of T. brasiliensis may be related to the existence of phenotypic plasticity, and variations in size and shape may be associated with different ecotopes, possibly as a result of conditions in each micro-habitat, such as temperature, relative humidity, food supply and density.

PGC1α gene Gly482Ser polymorphism predicts improved metabolic, inflammatory and vascular outcomes following bariatric surgery.

AIMS/HYPOTHESIS: Bariatric surgery is currently employed as an effective approach to treat class III obesity and class II obesity with co-morbidities. Unfortunately, the general anthropometric and metabolic outcomes of the surgery are not homogeneous, and defining the eligibility criteria that allow for a more precise prediction of the outcomes of this invasive procedure will refine the selection of patients. Here we tested the hypothesis that the Gly482Ser polymorphism of the ppargc1a gene would predict different outcomes following bariatric surgery. METHODS: Fifty-five patients (26 Gly/Gly and 29 Gly/Ser+Ser/Ser) selected for the Roux-en-Y gastric bypass according to the National Institutes of Health Consensus Statement criteria were followed up for 1 year, monitoring their anthropometric, metabolic and inflammatory parameters. RESULTS: Patients with the Gly482Ser polymorphism had significantly improved reductions in the waist/hip ratio, fasting blood glucose, C-reactive protein, blood leukocyte count, serum interleukin-6 and intima-media thickness of the carotid artery, as compared with Gly/Gly patients. CONCLUSIONS/INTERPRETATION: Thus, the Gly482Ser polymorphism may predict a more favorable metabolic and inflammatory outcome for obese patients submitted to bariatric surgery, leading to a reduced atherosclerotic risk.

Spatial carrier distribution in InP/GaAs type II quantum dots and quantum posts.

We performed a detailed investigation of the structural and optical properties of multi-layers of InP/GaAs quantum dots, which present a type II interface arrangement. Transmission electronic microscopy analysis has revealed relatively large dots that coalesce forming so-called quantum posts when the GaAs layer between the InP layers is thin. We observed that the structural properties and morphology affect the resulting radiative lifetime of the carriers in our systems. The carrier lifetimes are relatively long, as expected for type II systems, as compared to those observed for single layer InP/GaAs quantum dots. The interface intermixing effect has been pointed out as a limiting factor for obtaining an effective spatial separation of electrons and holes in the case of single layer InP/GaAs quantum-dot samples. In the present case this effect seems to be less critical due to the particular carrier wavefunction distribution along the structures.

Influência do manejo higiênico-sanitário na infecção por helmintos gastrintestinais em suínos de granjas tecnificadas e de subsistência abatidos na região metropolitana de Recife e Zona da Mata do estado de Pernambuco, Brasil / Influence of hygiene management on gastrointestinal helminth infection in pigs in metropolitan Recife and the Coastal Zone of the state of Pernambuco, Brazil

Objetivou-se com este trabalho analisar a influência do manejo higiênico-sanitário nos níveis de infecção por parasitos gastrintestinais em suínos de granjas tecnificadas e de subsistência abatidos na Região Metropolitana de Recife e Zona da Mata do Estado de Pernambuco. Para isso, o processo de abate de suínos em três abatedouros inscritos no sistema de inspeção estadual foi acompanhado durante o período de julho de 2008 a maio de 2009, num total de 447 suínos oriundos de 11 propriedades de municípios do Estado de Pernambuco, sendo oito granjas tecnificadas e três de subsistência. Amostras fecais foram coletadas da ampola retal no abatedouro e avaliadas pelos métodos de Gordon & Whitlock e Roberts & O´Sullivan. Realizou-se a aplicação de um questionário investigativo para conhecer a situação das granjas. Para o OPG a positividade foi de 2,7% (12/447), sendo 2,5% (11/447) para ovos tipo Strongyloidea e 0,2% (1/447) para Trichuris sp. Para a coprocultura, 5,5% (19/349) foram positivas para helmintos, sendo 2,9% (10/349) para Hyostrongylus sp., 0,3% (1/349) para Trichostrongylus sp., 2,0% (7/349) para Oesophagostomum spp. e infecção mista por Hyostrongylus sp. e Oesophagostomum spp. em 0,3% (1/349). Associação significativa (p < 0,05) com a ocorrência de helmintos foi obtida para as variáveis "gênero de helminto", "alimentação", "assistência veterinária", "quarentena", "comércio de animais vivos", "anti-helmíntico", "fonte de água", "tratamento de água", "qualidade de higiene das baias", "limpeza das instalações" e "conhecimento de verminose e manchas leitosas", com percentuais de positividade significativamente mais elevados entre os animais das granjas de subsistência.

The aim of the present study was to analyze the influence of management systems at intensive high-tech farms and subsistence farms on the prevalence of swine gastrointestinal helminthes in metropolitan Recife and the coastal zone of the state of Pernambuco, Brazil. For such, the slaughtering process at three slaughterhouses registered with the state inspection system was followed up between July 2008 to May 2009, totaling 447 pigs from 11 properties (8 high-tech farms and 3 subsistence farms). Fecal samples were collected and the parasitological examinations were carried out using the modified McMaster technique and coproculture for identification of larvae. A questionnaire was administered to determine the management condition of each farm. Strongyloidea eggs were present in 2.5% (11/447) of the pigs, and 0.2% (1/447) were positive for Trichuris sp. Coproculture revealed that 5.5% (19/349) were positive for helminthes, 2.9% (10/349) for Hyostrongylus sp., 0.3% (1/349) for Trichostrongylus sp., 2.0% (7/349) for Oesophagostomum sp., and 0.3% (1/349) with mixed infection by Hyostrongylus and Oesophagostomum sp. The occurrence of helminthes was significantly associated (p < 0.05) with helminth gender, feeding, veterinary care, quarantine, live animal trade, anti-helminth agents, water supply, water treatment, hygiene quality of stalls, dung removal frequency and knowledge regarding worms and milk spots. The percentages of positivity were significantly higher among animals on the subsistence farms.

INFLUÊNCIA DO MANEJO HIGIÊNICO-SANITÁRIO NA INFECÇÃO POR HELMINTOS GASTRINTESTINAIS EM SUÍNOS DE GRANJAS TECNIFICADAS E DE SUBSISTÊNCIA ABATIDOS NA REGIÃO METROPOLITANA DE RECIFE E ZONA DA MATA DO ESTADO DE PERNAMBUCO, BRASIL

ABSTRACT The aim of the present study was to analyze the influence of management systems at intensive high-tech farms and subsistence farms on the prevalence of swine gastrointestinal helminthes in metropolitan Recife and the coastal zone of the state of Pernambuco, Brazil. For such, the slaughtering process at three slaughterhouses registered with the state inspection system was followed up between July 2008 to May 2009, totaling 447 pigs from 11 properties (8 high-tech farms and 3 subsistence farms). Fecal samples were collected and the parasitological examinations were carried out using the modified McMaster technique and coproculture for identification of larvae. A questionnaire was administered to determine the management condition of each farm. Strongyloidea eggs were present in 2.5% (11/447) of the pigs, and 0.2% (1/447) were positive for Trichuris sp. Coproculture revealed that 5.5% (19/349) were positive for helminthes, 2.9% (10/349) for Hyostrongylus sp., 0.3% (1/349) for Trichostrongylus sp., 2.0% (7/349) for Oesophagostomum sp., and 0.3% (1/349) with mixed infection by Hyostrongylus and Oesophagostomum sp. The occurrence of helminthes was significantly associated (p 0.05) with helminth gender, feeding, veterinary care, quarantine, live animal trade, anti-helminth agents, water supply, water treatment, hygiene quality of stalls, dung removal frequency and knowledge regarding worms and milk spots. The percentages of positivity were significantly higher among animals on the subsistence farms.

RESUMO Objetivou-se com este trabalho analisar a influência do manejo higiênico-sanitário nos níveis de infecção por parasitos gastrintestinais em suínos de granjas tecnificadas e de subsistência abatidos na Região Metropolitana de Recife e Zona da Mata do Estado de Pernambuco. Para isso, o processo de abate de suínos em três abatedouros inscritos no sistema de inspeção estadual foi acompanhado durante o período de julho de 2008 a maio de 2009, num total de 447 suínos oriundos de 11 propriedades de municípios do Estado de Pernambuco, sendo oito granjas tecnificadas e três de subsistência. Amostras fecais foram coletadas da ampola retal no abatedouro e avaliadas pelos métodos de Gordon & Whitlock e Roberts & O´Sullivan. Realizou-se a aplicação de um questionário investigativo para conhecer a situação das granjas. Para o OPG a positividade foi de 2,7% (12/447), sendo 2,5% (11/447) para ovos tipo Strongyloidea e 0,2% (1/447) para Trichuris sp. Para a coprocultura, 5,5% (19/349) foram positivas para helmintos, sendo 2,9% (10/349) para Hyostrongylus sp., 0,3% (1/349) para Trichostrongylus sp., 2,0% (7/349) para Oesophagostomum spp. e infecção mista por Hyostrongylus sp. e Oesophagostomum spp. em 0,3% (1/349). Associação significativa (p 0,05) com a ocorrência de helmintos foi obtida para as variáveis gênero de helminto, alimentação, assistência veterinária, quarentena, comércio de animais vivos, anti-helmíntico, fonte de água, tratamento de água, qualidade de higiene das baias, limpeza das instalações e conhecimento de verminose e manchas leitosas, com percentuais de positividade significativamente mais elevados entre os animais das granjas de subsistência.

Could the bug Triatoma sherlocki be vectoring Chagas disease in small mining communities in Bahia, Brazil?

Searches for Chagas disease vectors were performed at the type locality from which Triatoma sherlocki Papa et al. (Hemiptera: Reduviidae: Triatominae) was described in the municipality of Gentio do Ouro, in the state of Bahia, Brazil, and in a small artisan quarry-mining community approximately 13 km distant in a remote area of the same municipality. The latter site represents a new locality record for this species. Adults, nymphs and exuviae of T. sherlocki were found in 21% of human dwellings, indicating that the species is in the process of domiciliation. Prevalence of Trypanosoma cruzi infection in collected bugs was 10.8%. Simple predictive approaches based on environmental similarity were used to identify additional sites likely suitable for this species. The approach successfully predicted an additional five sites for the species in surrounding landscapes. Ecological and entomological indicators were combined to discuss whether this scenario likely represents an isolated case or an emerging public health problem.

Doppler velocimetry of the uterine, umbilical and fetal middle cerebral arteries in pregnant women undergoing tocolysis with oral nifedipine.

OBJECTIVES: To evaluate Doppler velocimetry (resistance index (RI) and peak systolic velocity (PSV)) in the maternal-fetal circulation before and 5 and 24 h after tocolysis with oral nifedipine. METHODS: This was a prospective, observational, analytic cohort study performed in 47 pregnant women undergoing nifedipine tocolysis, each subject acting as her own control. Doppler assessment of uterine, umbilical and fetal middle cerebral (MCA) arteries was performed before and 5 and 24 h after an initial 20-mg sublingual dose, which was repeated twice at 20-min intervals if contractions failed to diminish. The maintenance dose consisted of 20 mg orally every 6 h for 24 h up to a total of 100-120 mg nifedipine. We analyzed whether there was a time effect and compared values at the different time-points. RESULTS: The MCA-RI had decreased significantly after 24 h of tocolysis (0 h = 0.85; 5 h = 0.85; 24 h = 0.81; P = 0.001), with no differences in uterine or umbilical arteries or in the MCA to umbilical artery ratio. The MCA-PSV had reduced significantly after 5 h (0 h = 41.5 cm/s; 5 h = 34.7 cm/s; P = 0.001), returning close to baseline levels between 5 and 24 h. The PSV increased significantly between 5 and 24 h in the right uterine artery (5 h = 55.1 cm/s; 24 h = 65.0 cm/s; P = 0.037) and in the umbilical artery (5 h = 28.4 cm/s; 24 h = 33.1 cm/s; P = 0.038). CONCLUSIONS: Nifedipine tocolysis is associated with a reduction in RI in the MCA but not in the uterine or umbilical arteries, a reduction in PSV in the MCA after 5 h but returning to baseline within 24 h, and an increase in PSV between 5 and 24 h in the umbilical and right uterine arteries.

Gentle handling temporarily increases c-Fos in the substantia nigra pars compacta.

Dopaminergic neurotransmission is involved in the regulation of sleep. In particular, the nigrostriatal pathway is an important center of sleep regulation. We hypothesized that dopaminergic neurons located in substantia nigra pars compacta (SNpc) could be activated by gentle handling, a method to obtain sleep deprivation (SD). Adult male C57/BL6J mice (N = 5/group) were distributed into non-SD (NSD) or SD groups. SD animals were subjected to SD once for 1 or 3 h by gentle handling. Two experiments were performed. The first determined the activation of SNpc neurons after SD, and the second examined the same parameters after pharmacologically induced dopaminergic depletion using intraperitoneal reserpine (2 mg/kg). After 1 or 3 h, SD and NSD mice were subjected to motor evaluation using the open field test. Immediately after the behavioral test, the mice were perfused intracardially to fix the brain and for immunohistochemical analysis of c-Fos protein expression within the SNpc. The open field test indicated that SD for 1 or 3 h did not modify motor behavior. However, c-Fos protein expression was increased after 1 h of SD compared with the NSD and 3-h SD groups. These immunohistochemistry data indicate that these periods of SD are not able to produce dopaminergic supersensitivity. Nevertheless, the increased expression of c-Fos within the SNpcsuggests that dopaminergic nigral activation was triggered by SD earlier than motor responsiveness. Dopamine-depleted mice(experiment 2) exhibited a similar increase of c-Fos expression compared to control animals indicating that dopamine neurons are still activated in the 1-h SD group despite the exhaustion of dopamine. This finding suggests that this range (2-5-fold) of neuronal activation may serve as a marker of SD.

Gentle handling temporarily increases c-Fos in the substantia nigra pars compacta

Dopaminergic neurotransmission is involved in the regulation of sleep. In particular, the nigrostriatal pathway is an important center of sleep regulation. We hypothesized that dopaminergic neurons located in substantia nigra pars compacta (SNpc) could be activated by gentle handling, a method to obtain sleep deprivation (SD). Adult male C57/BL6J mice (N = 5/group) were distributed into non-SD (NSD) or SD groups. SD animals were subjected to SD once for 1 or 3 h by gentle handling. Two experiments were performed. The first determined the activation of SNpc neurons after SD, and the second examined the same parameters after pharmacologically induced dopaminergic depletion using intraperitoneal reserpine (2 mg/kg). After 1 or 3 h, SD and NSD mice were subjected to motor evaluation using the open field test. Immediately after the behavioral test, the mice were perfused intracardially to fix the brain and for immunohistochemical analysis of c-Fos protein expression within the SNpc. The open field test indicated that SD for 1 or 3 h did not modify motor behavior. However, c-Fos protein expression was increased after 1 h of SD compared with the NSD and 3-h SD groups. These immunohistochemistry data indicate that these periods of SD are not able to produce dopaminergic supersensitivity. Nevertheless, the increased expression of c-Fos within the SNpc suggests that dopaminergic nigral activation was triggered by SD earlier than motor responsiveness. Dopamine-depleted mice (experiment 2) exhibited a similar increase of c-Fos expression compared to control animals indicating that dopamine neurons are still activated in the 1-h SD group despite the exhaustion of dopamine. This finding suggests that this range (2-5-fold) of neuronal activation may serve as a marker of SD.

Lack of association of GSTT1, GSTM1, GSTO1, GSTP1 and CYP1A1 polymorphisms for susceptibility and outcome in Brazilian prostate cancer patients.

The polymorphic inheritance of human drug-metabolizing enzymes, such as those encoded by the GST and CYP systems, has been implicated in both cancer risk and prognostic. In an effort to increase our understanding of the interaction between potential environmental exposure, lifestyle, and genetic factors in the predisposition and response to radiotherapy of prostate cancer patients, we examined GSTT1, GSTM1, GSTO1, GSTP1 and CYP1A1 genotypes in a Brazilian population. We studied 125 prostate cancer patients and 100 benign prostatic hyperplasia patients paired for ethnic and lifestyle characteristics. Lifetime occupational history, dietary patterns, cigarette-smoking, and other anamnestic data were obtained through interviews. Outcome was evaluated in 42 stage