Sarcoplasmic reticulum calcium ATPase (SERCA) proteolysis by matrix metalloproteinase-2 contributes to vascular dysfunction in early hypertension.

AIMS: Hypertension is associated with an increased activity of matrix metalloproteinase (MMP)-2 in the vasculature, which, in turn, proteolyzes extra- and intracellular proteins that lead to vascular dysfunction. The activity of sarcoplasmic reticulum calcium ATPase (SERCA) is decreased in the aortas of hypertensive rats. Increased activity of MMP-2 proteolyzed SERCA in rat heart during ischemia and reperfusion injury, thus impairing cardiac function. Therefore, we examined whether increased activity of MMP-2 in early hypertension contributes to proteolyze SERCA in the aortas, thus leading to maladaptive vascular remodeling and dysfunction. MAIN METHODS: Male Sprague-Dawley rats were submitted to two kidney-one clip (2K-1C) or Sham surgery and treated with doxycycline. Systolic blood pressure (SBP) was assessed by tail-cuff plethysmography. After 7 days, aortas were collected for zymography assays, Western blot to SERCA, ATPase activity assay, vascular reactivity, Ki-67 immunofluorescence and hematoxylin/eosin stain. KEY FINDINGS: SBP was increased in 2K-1C rats and doxycycline did not reduce it, but decreased MMP-2 activity and prevented SERCA proteolysis in aortas. Cross sectional area, media to lumen ratio and Ki-67 were all increased in the aortas of hypertensive rats and doxycycline decreased Ki-67. In 2K-1C rats, arterial relaxation to acetylcholine was impaired and doxycycline ameliorated it. SIGNIFICANCE: doxycycline reduced MMP-2 activity in aortas of 2K-1C rats and prevented proteolysis of SERCA and its dysfunction, thus ameliorating hypertension-induced vascular dysfunction.

Spectroscopic behavior of bufotenine and bufotenine N-oxide: Solvent and pH effects and interaction with biomembrane models.

Bufotenine is a fluorescent analog of Dimethyltryptamine (DMT) that has been widely studied due to its psychedelic properties and biological activity. However, little is known about its spectroscopic properties in different media. Thus, we present in this work, for the first time, the spectroscopic behavior of bufotenine and bufotenine N-oxide by means of their fluorescence properties. Both molecules exhibit changes in optical absorption and emission spectra with variations in pH of the medium and in different solvents. Assays in the presence of biomembranes models, like micelles and liposomes, were also performed. In surfactants titration experiments, the spectral shift observed in fluorescence shows the interaction of both molecules with pre-micellar structures and with micelles. Steady state anisotropy measurements show that both bufotenine and bufotenine N-oxide, in the studied concentration range, interact with liposomes without causing changes in the fluidity of the lipid bilayer. These results can be useful in studies that aim at searching for new compounds, inspired by bufotenine and bufotenine N-oxide, with relevant pharmacological activities and also in studies that use these molecules as markers of psychiatric disorders.

Lipid profile and reproductive performance of female offspring of SWISS mouse females supplemented with resveratrol or canjiqueira (Byrsonima cydoniifolia A Juss) during gestation.

This study aimed to resveratrol supplementation (at 5 or 10 mg/kg) and a hydroethanolic extract of canjiqueira fruits (150 mg/kg) on female SWISS mice. Total cholesterol, high-density lipoprotein (HDL), triglyceride levels, gestation rates, and embryonic implantation rates in their female Offspring was evaluated. In conclusion, the consumption of canjiqueira fruit extract altered the lipid profile of their female offspring, and did not impact their reproductive performance. Supplementing female SWISS mice with 10 mg/kg of resveratrol increased total cholesterol, triglycerides, and HDL levels, thereby enhancing the reproductive efficiency of their offspring.

Added value of corpus callosotomy following vagus nerve stimulation in children with Lennox-Gastaut syndrome: A multicenter, multinational study.

OBJECTIVE: Lennox-Gastaut syndrome (LGS) is a severe form of epileptic encephalopathy, presenting during the first years of life, and is very resistant to treatment. Once medical therapy has failed, palliative surgeries such as vagus nerve stimulation (VNS) or corpus callosotomy (CC) are considered. Although CC is more effective than VNS as the primary neurosurgical treatment for LGS-associated drop attacks, there are limited data regarding the added value of CC following VNS. This study aimed to assess the effectiveness of CC preceded by VNS. METHODS: This multinational, multicenter retrospective study focuses on LGS children who underwent CC before the age of 18 years, following prior VNS, which failed to achieve satisfactory seizure control. Collected data included epilepsy characteristics, surgical details, epilepsy outcomes, and complications. The primary outcome of this study was a 50% reduction in drop attacks. RESULTS: A total of 127 cases were reviewed (80 males). The median age at epilepsy onset was 6 months (interquartile range [IQR] = 3.12-22.75). The median age at VNS surgery was 7 years (IQR = 4-10), and CC was performed at a median age of 11 years (IQR = 8.76-15). The dominant seizure type was drop attacks (tonic or atonic) in 102 patients. Eighty-six patients underwent a single-stage complete CC, and 41 an anterior callosotomy. Ten patients who did not initially have a complete CC underwent a second surgery for completion of CC due to seizure persistence. Overall, there was at least a 50% reduction in drop attacks and other seizures in 83% and 60%, respectively. Permanent morbidity occurred in 1.5%, with no mortality. SIGNIFICANCE: CC is vital in seizure control in children with LGS in whom VNS has failed. Surgical risks are low. A complete CC has a tendency toward better effectiveness than anterior CC for some seizure types.

A comparative phylogenomic analysis of birds reveals heterogeneous differentiation processes among Neotropical savannas.

The main objective of this study was to evaluate biogeographical hypotheses of diversification and connection between isolated savannas north (Amazonian savannas) and south (Cerrado core) of the Amazon River. To achieve this, we used genomic markers (genotyping-by-sequencing) to evaluate the genetic structure, population phylogenetic relationships and historical range shifts of four Neotropical passerines with peri-Atlantic distributions: the narrow-billed woodcreeper (Lepidocolaptes angustirostris), the plain-crested elaenia (Elaenia cristata), the grassland sparrow (Ammodramus humeralis) and the white-banded tanager (Neothraupis fasciata). Population genetic analyses indicated that landscape (e.g., geographic distance, landscape resistance and percentage of tree cover) and climate metrics explained divergence among populations in most species, but without indicating a differential role between current and historical factors. Our results did not fully support the hypothesis that isolated populations in Amazonian savannas have been recently derived from the Cerrado core domain. Intraspecific phylogenies and gene flow analyses supported multiple routes of connection between the Cerrado and Amazonian savannas, rejecting the hypothesis that the Atlantic corridor explains the peri-Atlantic distribution. Our results reveal that the biogeographical history of the region is complex and cannot be explained by simple vicariant models.

Midline Brain Shift After Hemispheric Surgery: Natural History, Clinical Significance, and Association With Cerebrospinal Fluid Diversion.

BACKGROUND: Hemispherectomy and its modern variants are effective surgical treatments for medically intractable unihemispheric epilepsy. Although some complications such as posthemispherectomy hydrocephalus are well documented, midline brain shift (MLBS) after hemispheric surgery has only been described anecdotally and never formally studied. OBJECTIVE: To assess the natural history and clinical relevance of MLBS and determine whether cerebrospinal fluid (CSF) shunting of the ipsilateral surgical cavity exacerbates MLBS posthemispheric surgery. METHODS: A retrospective review of consecutive pediatric patients who underwent hemispheric surgery for intractable epilepsy and at least 6 months of follow-up at UCLA between 1994 and 2018 was performed. Patients were grouped by MLBS severity, shunt placement, valve type, and valve opening pressure (VOP). MLBS was evaluated using the paired samples t-test and analysis of covariance adjusting for follow-up time and baseline postoperative MLBS. RESULTS: Seventy patients were analyzed, of which 23 (33%) required CSF shunt placement in the ipsilateral surgical cavity for posthemispherectomy hydrocephalus. MLBS increased between first and last follow-up for nonshunted (5.3 ± 4.9-9.7 ± 6.6 mm, P < .001) and shunted (6.6 ± 3.5-16.3 ± 9.4 mm, P < .001) patients. MLBS progression was greater in shunted patients (P = .001). Shunts with higher VOPs did not increase MLBS relative to nonshunted patients (P = .834), whereas MLBS increased with lower VOPs (P = .001). Severe MLBS was associated with debilitating headaches (P = .048). CONCLUSION: Patients undergoing hemispheric surgery often develop postoperative MLBS, ie, exacerbated by CSF shunting of the ipsilateral surgical cavity, specifically when using lower VOP settings. MLBS exacerbation may be related to overshunting. Severe MLBS is associated with debilitating headaches.

Epilepsy surgery in infants up to 3 months of age: Safety, feasibility, and outcomes: A multicenter, multinational study.

OBJECTIVE: Drug-resistant epilepsy (DRE) during the first few months of life is challenging and necessitates aggressive treatment, including surgery. Because the most common causes of DRE in infancy are related to extensive developmental anomalies, surgery often entails extensive tissue resections or disconnection. The literature on "ultra-early" epilepsy surgery is sparse, with limited data concerning efficacy controlling the seizures, and safety. The current study's goal is to review the safety and efficacy of ultra-early epilepsy surgery performed before the age of 3 months. METHODS: To achieve a large sample size and external validity, a multinational, multicenter retrospective study was performed, focusing on epilepsy surgery for infants younger than 3 months of age. Collected data included epilepsy characteristics, surgical details, epilepsy outcome, and complications. RESULTS: Sixty-four patients underwent 69 surgeries before the age of 3 months. The most common pathologies were cortical dysplasia (28), hemimegalencephaly (17), and tubers (5). The most common procedures were hemispheric surgeries (48 procedures). Two cases were intentionally staged, and one was unexpectedly aborted. Nearly all patients received blood products. There were no perioperative deaths and no major unexpected permanent morbidities. Twenty-five percent of patients undergoing hemispheric surgeries developed hydrocephalus. Excellent epilepsy outcome (International League Against Epilepsy [ILAE] grade I) was achieved in 66% of cases over a median follow-up of 41 months (19-104 interquartile range [IQR]). The number of antiseizure medications was significantly reduced (median 2 drugs, 1-3 IQR, p < .0001). Outcome was not significantly associated with the type of surgery (hemispheric or more limited resections). SIGNIFICANCE: Epilepsy surgery during the first few months of life is associated with excellent seizure control, and when performed by highly experienced teams, is not associated with more permanent morbidity than surgery in older infants. Thus surgical treatment should not be postponed to treat DRE in very young infants based on their age.

Knowledge of Zika Virus Transmission and Its Prevention among High-Risk Pregnant Women in Brazil.

Recent outbreaks of Zika virus (ZIKV) infection highlight the urgent need to evaluate the efficacy of current public health measures to educate susceptible groups about how to prevent infection, modes of viral transmission, and consequences of infection. We performed a cross-sectional study in the city of Jundiaí, São-Paulo, from March 2016 to August 2017. In 315 high-risk pregnant women we evaluated the rate of ZIKV infection, knowledge of pathways of ZIKV transmission, and the use of protective measures. Data were analyzed and correlated with sociodemographic variables. The rate of ZIKV infection was 10.8%. ZIKV transmission by mosquitoes was the best-known means of virus acquisition, while transmission of ZIKV by sexual intercourse as well as mother-fetus transmission was known by less than half of the women. The use of insect repellent, reported by 53% of participants, was correlated with higher education and personal directives from health professionals. Condom use was reported by 19.5% of subjects. Improved strategies to increase awareness of ZIKV infection and its consequences, designed to appeal to specific, targeted populations, are clearly necessary to more accurately prevent the spread of this infection and diminish adverse consequences in the pregnant population.

Chronic serotonin reuptake inhibition uncouples brown fat mitochondria and induces beiging/browning process of white fat in overfed rats.

AIM: To investigate whether a chronic 5-HT reuptake inhibitor (i.e. Fluoxetine-FLX) exposure in young adult rats overfed during suckling period would modulate interscapular brown adipose tissue (iBAT) mitochondria and browning agents in white adipose tissue (WAT). METHODS: Male Wistar rats were assigned into either a normofed group (n = 9 per group) or an overfed group (n = 3 per group) induced by litter size reduction at postnatal day 3 (PND3). Pharmacological manipulation was carried out between PND39 and PND59 and groups were assigned accordingly: Normofed + vehicle solution - NaCl 0.9% (NV group), normofed + FLX solution - 10 mg/kg b.w. (NF group), overfed + vehicle (OV group) and overfed + FLX (OF group). We evaluated mitochondrial oxygen consumption and reactive species (RS) production, oxidative stress analyses (MDA concentration, carbonyl content, REDOX state [GSH/GSSG], global oxy score) in the iBAT, gene (leptin, Ucp1, Sirt1, Pgc1α and Prdm16) and protein (UCP1) expression in the iBAT and epididymal WAT (eWAT). KEY FINDINGS: OV group increased body weight gain, Lee index and oxidative stress in the iBAT. Both FLX-treated groups showed less weight gain compared to their controls. OF group showed different leptin expression in the WAT and iBAT; increased functional UCP1 content and mitochondrial activity with less oxidative stress in the iBAT and upregulation of browning genes in eWAT (Pgc1α, Prdm16 and Ucp1). CONCLUSION: Altogether our findings indicated that FLX treatment in young adult overfed animals improved the iBAT mitochondrial function, reduced oxidative stress and induced transcriptional activation of browning agents in white adipose tissue.

High-Protein Diet Associated with Bocaiuva Supplementation Decreases Body Fat and Improves Glucose Tolerance in Resistance-Trained Rats.

High-protein diets (HPDs) are widely used for health and performance. However, the combination of whey protein and natural foods (i.e., fruits) is still unclear. Thus, we evaluated the role of supplemental HPD with Bocaiuva (Acrocomia sp.) in metabolic and body composition parameters of rats submitted to resistance training (RT). Wistar rats (203.3 ± 30 g) were randomly allocated to five groups: normoproteic control (CON, n = 5), sedentary high-protein (SH, n = 5), RT + H (trained high-protein [TH], n = 5), sedentary+Bocaiuva (SH+B, n = 4), and RT+Bocaiuva (TH+B, n = 4) diet groups. After 12 weeks of RT, the maximal strength increased in both trained groups (P < .05). The TH + B group had lower values of adiposity index (AI) (3.8 ± 0.7% vs. 6.8 ± 1.3%) and visceral fat (0.038 ± 0.004 g/g vs. 0.067 ± 0.012 g/g) compared with the SH group, respectively (P < .05). The other groups did not show differences in values of AI (CON, 5.4 ± 1.6%, TH, 5.4 ± 1.3%, and SH+B, 5.5 ± 1.2%). In addition, the fasting glucose of trained groups (TH, 106.0 ± 4.5, and TH+B, 100.4 ± 13.5 dL/mg) was significantly lower when compared with controls (SH, 120.0 ± 14.4, and SH+B, 119 ± 6.4 dL/mg) (P < .05). Bocaiuva combined with an HPD reduced visceral fat and AI in addition to improving glucose tolerance of rats submitted to RT.

Evaluation of Level of Essential Elements and Toxic Metal in the Medicinal Plant Hymenaea martiana Hayne (Jatobá) Used by Mid-West Population of Brazil.

Hymenaea martiana Hayne belongs to the family Fabaceae (Leguminosae) and presents the popular name of jatobá. It is a tree that demonstrates medicinal purposes and represents a food source in Brazil. The potential contribution of each species to recommended nutrient intakes (DRI) and Brazilian Health Surveillance Agency (ANVISA) for children and adults were calculated. A comparison between the quantified contents of micro- and macronutrients Al, Ca, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, P, S, and Zn in leaves tea and tea of the bark of this plant was made with the recommendation of FDA and ANVISA. General safety regarding metal content (Na, K, Ca, Fe, Zn, and Ni) and nonmetal (P) was assured as none of them exceed the safety limit of the daily intake. However, the content of Mn observed in the teas of H. martiana Hayne is above the UL for tolerable intake level for children aged 1-6 years. There are no limits established for the UL of Cr and S for children and adults. The data on quantification of mineral concentration in the species Hymenaea martiana Hayne obtained can serve as a tool to decide the dosage of preparations from this plant used for medicinal purposes.

Nutraceutical Potential of Carica papaya in Metabolic Syndrome.

Carica papaya L. is a well-known fruit worldwide, and its highest production occurs in tropical and subtropical regions. The pulp contains vitamins A, C, and E, B complex vitamins, such as pantothenic acid and folate, and minerals, such as magnesium and potassium, as well as food fibers. Phenolic compounds, such as benzyl isothiocyanate, glucosinolates, tocopherols (α and δ), ß-cryptoxanthin, ß-carotene and carotenoids, are found in the seeds. The oil extracted from the seed principally presents oleic fatty acid followed by palmitic, linoleic and stearic acids, whereas the leaves have high contents of food fibers and polyphenolic compounds, flavonoids, saponins, pro-anthocyanins, tocopherol, and benzyl isothiocyanate. Studies demonstrated that the nutrients present in its composition have beneficial effects on the cardiovascular system, protecting it against cardiovascular illnesses and preventing harm caused by free radicals. It has also been reported that it aids in the treatment of diabetes mellitus and in the reduction of cholesterol levels. Thus, both the pulp and the other parts of the plant (leaves and seeds) present antioxidant, anti-hypertensive, hypoglycemic, and hypolipidemic actions, which, in turn, can contribute to the prevention and treatment of obesity and associated metabolic disorders.

Antiproliferative Activity of Extracts of Campomanesia adamantium (Cambess.) O. Berg and Isolated Compound Dimethylchalcone Against B16-F10 Murine Melanoma.

Campomanesia adamantium, a native species of the Brazilian Cerrado, is characterized as a natural source of phenolic compounds and has known potential anticancer activities. This study aimed to evaluate the chemical profile of dichloromethane extracts of pulp (DEGPU) and peel (DEGPE) from the fruits of C. adamantium and to identify compounds with antiproliferative effects in vitro against melanoma cells by sulforhodamine B (SRB) assay, apoptosis induction assay, caspase-3 activation assay, nitric oxide (NO) release in coculture of B16-F10 cells and murine peritoneal macrophages. The chemical profiles of DEGPU and DEGPE were analyzed by high performance liquid chromatography coupled to diode array detector and mass spectrometer using the electrospray ionization interface (HPLC-DAD-ESI-MS/MS). Thirteen compounds were identified in both extracts and the chromatographic study of the most active extract in SRB assay DEGPU (GI50 of 16.17 µg/mL) resulted in the isolation of seven compounds. The isolated compound dimethylchalcone (DMC) had the highest antiproliferative activity against B16-F10 with a GI50 of 7.11 µg/mL. DEGPU extract activated caspase-3 in 29% of cells at 25 µg/mL and caused a 50% decrease in NO release in coculture. DEGPU can be characterized as a source of bioactive compounds such as DMC, as seen from its antiproliferative effect in vitro by inducing B16-F10 cells to undergo apoptosis, essential feature in the search for new anticancer drugs.

Protective effects of estrogen against cardiovascular disease mediated via oxidative stress in the brain.

During their reproductive years women produce significant levels of estrogens, predominantly in the form of estradiol, that are thought to play an important role in cardioprotection. Mechanisms underlying this action include both estrogen-mediated changes in gene expression, and post-transcriptional activation of protein signaling cascades in the heart and in neural centers controlling cardiovascular function, in particular, in the brainstem. There, specific neurons, especially those of the bulbar region play an important role in the neuronal control of the cardiovascular system because they control the outflow of sympathetic activity and parasympathetic activity as well as the reception of chemical and mechanical signals. In the present review, we discuss how estrogens exert their cardioprotective effect in part by modulating the actions of internally generated products of cellular oxidation such as reactive oxygen species (ROS) in brain stem neurons. The significance of this review is in integrating the literature of oxidative damage in the brain with the literature of neuroprotection by estrogen in order to better understand both the benefits and limitations of using this hormone to prevent cardiovascular disease.

Spatiotemporal Image Correlation Analysis for 3D Flow Field Mapping in Microfluidic Devices.

Microfluidic devices reproducing 3D networks are particularly valuable for nanomedicine applications such as tissue engineering and active cell sorting. There is however a gap in the possibility to measure how the flow evolves in such 3D structures. We show here that it is possible to map 3D flows in complex microchannel networks by combining wide field illumination to image correlation approaches. For this purpose, we have derived the spatiotemporal image correlation analysis of time stacks of single-plane illumination microscopy images. From the detailed analytical and numerical analysis of the resulting model, we developed a fitting method that allows us to measure, besides the in-plane velocity, the out-of-plane velocity component down to vz ≅ 65 µm/s. We have applied this method successfully to the 3D reconstruction of flows in microchannel networks with planar and 3D ramifications. These different network architectures have been realized by exploiting the great prototyping ability of a 3D printer, whose precision can reach few tens of micrometers, coupled to poly dimethyl-siloxane soft-printing lithography.

Image Cross-Correlation Analysis of Time Varying Flows.

In vivo studies of blood circulation pathologies have great medical relevance and need methods for the characterization of time varying flows at high spatial and time resolution in small animal models. We test here the efficacy of the combination of image correlation techniques and single plane illumination microscopy (SPIM) in characterizing time varying flows in vitro and in vivo. As indicated by numerical simulations and by in vitro experiments on straight capillaries, the complex analytical form of the cross-correlation function for SPIM detection can be simplified, in conditions of interest for hemodynamics, to a superposition of Gaussian components, easily amenable to the analysis of variable flows. The possibility to select a wide field of view with a good spatial resolution along the collection optical axis and to compute the cross-correlation between regions of interest at varying distances on a single time stack of images allows one to single out periodic flow components from spurious peaks on the cross-correlation functions and to infer the duration of each flow component. We apply this cross-correlation analysis to the blood flow in Zebrafish embryos at 4 days after fertilization, measuring the average speed and the duration of the systolic and diastolic phases.

Development of a water-in-oil-in-water multiple emulsion system integrating biomimetic aqueous-core lipid nanodroplets for protein entity stabilization. Part II: process and product characterization.

The aqueous-core enclosed in lipid nanoballoons integrating multiple emulsions of the type water-in-oil-in-water mimic, at least in theory, the environment within viable cells, thus being suitable for housing hydrophilic protein entities such as bioactive proteins, peptides and bacteriophage particles. This study reports a complete physicochemical characterization of optimized biomimetic aqueous-core lipid nanoballoons housing hydrophilic (BSA) protein entities, evolved from a statistical 23×31 factorial design study (three variables at two levels and one variable at three levels) that was the subject of the first paper of a series of three, aiming at complete stabilization of the three-dimensional structure of protein entities attempted via housing the said molecular entities within biomimetic aqueous-core lipid nanoballoons integrating a multiple (W/O/W) emulsion. The statistical factorial design followed led to the production of an optimum W/O/W multiple emulsion possessing quite homogeneous particles with an average hydrodynamic size of (186.2 ± 2.6) nm and average Zeta potential of (-36.5 ± 0.9) mV, and exhibiting a polydispersity index of 0.206 ± 0.014. Additionally, the results obtained for the diffusion coefficient of the lipid nanoballoons integrating the optimized W/O/W multiple emulsion were comparable and of the same order of magnitude (10-12 m2 s-1) as those published by other authors since, typically, diffusion coefficients for molecules range from 10-10 to 10-7 m2 s-1, but diffusion coefficients for nanoparticles are typically of the order of magnitude of 10-12 m2 s-1.

Saúde e protocolos de qualidade / Health and quality protocols

A aferição da qualidade da assistência hospitalar pode ser feita de inúmeras maneiras, entre as quais, a baseada em protocolos que permitem a criação, manutenção de valores e exemplos para profissionais, que interferirão na sua formação e na conduta diária frente ao paciente e à instituição, bem como comparação de resultados entre os serviços, melhorando-os continuamente. Na Secretaria de Estado da Saúde de São Paulo (SES/SP) iniciou-se trabalho de avaliação dos Hospitais de Ensino vinculados ao Sistema Único de Saúde (SUS) do Estado de São Paulo, certificados e contratualizados pelo sistema desde o início do processo, em 2004, instituído por comissão interinstitucional, composta por ministérios, SES/SP e entidades de classe. A partir de 2006, estão sendo avaliados indicadores de mortalidade, volume e utilidade destas unidades de ensino, bem como dos outros hospitais conveniados-SUS, que são comparados com indicadores selecionados do protocolo da Agency for Health care Research and Quality (AHRQ), dos Estados Unidos da América. Esta atividade tem sido importante no monitoramento das unidades, no retorno de informações para continuar aprimorando a qualidade da assistência, pesquisa e ensino. A série histórica conta atualmente com nove anos (2006 a 2014) e aponta melhoras dos indicadores, embora estejam abaixo da média encontrada nos estabelecimentos americanos...

Fructose affecting morphology and inducing ß-fructofuranosidases in Penicillium janczewskii.

Fructose, glucose, and an equimolar mixture of both sugars affected differently hyphae thickness, biomass production and secretion of ß-fructofuranosidase in Penicillium janczewskii. Reduced growth, thinner hyphae and visible injuries were early observed during fungal cultivation in fructose-containing medium, reaching the maximum between 12 and 15 days of culture. Total sugar content from the cell wall was lower when fructose was supplied and polysaccharides lower than 10 kDa predominated, regardless the culture age. Maximal inulinase and invertase activities were detected in culture filtrates after 12 days, excepting in the glucose-containing medium. Structural changes in cell walls coincided with the increase of extracellular enzyme activity in the fructose-containing medium. The fragility of the hyphae might be related with both low carbohydrate content and predominance of low molecular weight glucans in the walls. Data presented here suggest changes in carbohydrate component of the cell walls are induced by the carbon source.

CD11c(+) CD103(+) cells of Mycobacterium tuberculosis-infected C57BL/6 but not of BALB/c mice induce a high frequency of interferon-γ- or interleukin-17-producing CD4(+) cells.

The magnitude of the cellular adaptive immune response is critical for the control of Mycobacterium tuberculosis infection in the chronic phase. In addition, the genetic background is equally important for resistance or susceptibility to tuberculosis. In this study, we addressed whether lung populations of dendritic cells, obtained from genetically different hosts, would play a role in the magnitude and function of CD4(+) populations generated after M. tuberculosis infection. Thirty days post-infection, C57BL/6 mice, which generate a stronger interferon-γ (IFN-γ)-mediated immune response than BALB/c mice, exhibited a higher number and frequency of lung CD11c(+)  CD11b(-)  CD103(+) cells compared with BALB/c mice, which exhibited a high frequency of lung CD11c(+)  CD11b(+)  CD103(-) cells. CD11c(+)  CD11b(-)  CD103(+) cells, purified from lungs of infected C57BL/6 mice, but not from infected BALB/c mice, induced a higher frequency of IFN-γ-producing or interleukin-17 (IL-17)-producing CD4(+) cells. Moreover, CD4(+) cells also arrive at the lung of C57BL/6 mice faster than in BALB/c mice. This pattern of immune response seems to be associated with higher gene expression for CCL4, CCL19, CCL20 and CCR5 in the lungs of infected C57BL/6 mice compared with infected BALB/c mice. The results described here show that the magnitude of IFN-γ-producing or IL-17-producing CD4(+) cells is dependent on CD11c(+)  CD11b(-)  CD103(+) cells, and this pattern of immune response is directly associated with the host genetic background. Therefore, differences in the genetic background contribute to the identification of immunological biomarkers that can be used to design human assays to predict progression of M. tuberculosis infection.