Human fallopian tube: a new source of multipotent adult mesenchymal stem cells discarded in surgical procedures

Background: The possibility of using stem cells for regenerative medicine has opened a new field of investigation. The search for sources to obtain multipotent stem cells from discarded tissues or through non-invasive procedures is of great interest. It has been shown that mesenchymal stem cells (MSCs) obtained from umbilical cords, dental pulp and adipose tissue, which are all biological discards, are able to differentiate into muscle, fat, bone and cartilage cell lineages. The aim of this study was to isolate, expand, characterize and assess the differentiation potential of MSCs from human fallopian tubes (hFTs). Methods: Lineages of hFTs were expanded, had their karyotype analyzed, were characterized by flow cytometry and underwent in vitro adipogenic, chondrogenic, osteogenic, and myogenic differentiation. Results: Here we show for the first time that hFTs, which are discarded after some gynecological procedures, are a rich additional source of MSCs, which we designated as human tube MSCs (htMSCs). Conclusion: Human tube MSCs can be easily isolated, expanded in vitro, present a mesenchymal profile and are able to differentiate into muscle, fat, cartilage and bone in vitro.

Collagen Hydrolysate Intake Increases Skin Collagen Expression and Suppresses Matrix Metalloproteinase 2 Activity

The effect of daily ingestion of collagen hydrolysate (CH) on skin extracellular matrix proteins was investigated. Four-week-old male Wistar rats were fed a modified AIN-93 diet containing 12% casein as the reference group or CH as the treatment group. A control group was established in which animals were fed a non-protein-modified AIN-93 diet. The diets were administered continuously for 4 weeks when six fresh skin samples from each group were assembled and subjected to extraction of protein. Type I and IV collagens were studied by immunoblot, and activities of matrix metalloproteinase (MMP) 2 and 9 were assessed by zymography. The relative amount of type I and IV collagens was significantly (P<.05) increased after CH intake compared with the reference diet group (casein). Moreover, CH uptake significantly decreased both proenzyme and active forms of MMP2 compared with casein and control groups (P<.05). In contrast, CH ingestion did not influence on MMP9 activity. These results suggest that CH may reduce aging-related changes of the extracellular matrix by stimulating anabolic processes in skin tissue.

Induction of Heme Oxygenase-1 Can Halt and Even Reverse Renal Tubule-Interstitial Fibrosis

Background: The tubule-interstitial fibrosis is the hallmark of progressive renal disease and is strongly associated with inflammation of this compartment. Heme-oxygenase-1 (HO-1) is a cytoprotective molecule that has been shown to be beneficial in various models of renal injury. However, the role of HO-1 in reversing an established renal scar has not yet been addressed. Aim: We explored the ability of HO-1 to halt and reverse the establishment of fibrosis in an experimental model of chronic renal disease. Methods: Sprague-Dawley male rats were subjected to unilateral ureteral obstruction (UUO) and divided into two groups: non-treated and Hemin-treated. To study the prevention of fibrosis, animals were pre-treated with Hemin at days -2 and -1 prior to UUO. To investigate whether HO-1 could reverse established fibrosis, Hemin therapy was given at days 6 and 7 post-surgery. After 7 and/or 14 days, animals were sacrificed and blood, urine and kidney tissue samples were collected for analyses. Renal function was determined by assessing the serum creatinine, inulin clearance, proteinuria/creatininuria ratio and extent of albuminuria. Arterial blood pressure was measured and fibrosis was quantified by Picrosirius staining. Gene and protein expression of pro-inflammatory and pro-fibrotic molecules, as well as HO-1 were performed. Results: Pre-treatment with Hemin upregulated HO-1 expression and significantly reduced proteinuria, albuminuria, inflammation and pro-fibrotic protein and gene expressions in animals subjected to UUO. Interestingly, the delayed treatment with Hemin was also able to reduce renal dysfunction and to decrease the expression of pro-inflammatory molecules, all in association with significantly reduced levels of fibrosis-related molecules and collagen deposition. Finally, TGF-beta protein production was significantly lower in Hemin-treated animals. Conclusion: Treatment with Hemin was able both to prevent the progression of fibrosis and to reverse an established renal scar. Modulation of inflammation appears to be the major mechanism behind HO-1 cytoprotection.

Association of Trypanosoma vivax in extracellular sites with central nervous system lesions and changes in cerebrospinal fluid in experimentally infected goats

Changes in cerebrospinal fluid (CSF) and anatomical and histopathological central nervous system (CNS) lesions were evaluated, and the presence of Trypanosoma vivax in CNS tissues was investigated through PCR. Twelve adult male goats were divided into three groups (G): G1, infected with T. vivax and evaluated during the acute phase; G2, infected goats evaluated during the chronic phase; and G3, consisting of non-infected goats. Each goat from G1 and G2 was infected with 1.25 x 10(5) trypomastigotes. Cerebrospinal fluid (CSF) analysis and investigation of T. vivax was performed at the 15(th) day post-infection (dpi) in G1 goats and on the fifth day after the manifestation of nervous system infection signs in G2 goats. All goats were necropsied, and CNS fragments from G1 and G2 goats were evaluated by PCR for the determination of T. vivax. Hyperthermia, anemia and parasitemia were observed from the fifth dpi for G1 and G2, with the highest parasitemia peak between the seventh and 21(st) dpi. Nervous system infection signs were observed in three G2 goats between the 30(th) and 35(th) dpi. CSF analysis revealed the presence of T. vivax for G2. Meningitis and meningoencephalitis were diagnosed in G2. PCR were positive for T. vivax in all the samples tested. In conclusion, T. vivax may reach the nervous tissue resulting in immune response from the host, which is the cause of progressive clinical and pathological manifestations of the CNS in experimentally infected goats.

Supramolecular polymorphism of DNA in non-cationic L(alpha) lipid phases

The structure of a complex between hydrated DNA and a non-cationic lipid is studied, including its phase diagram. The complex is spontaneously formed by adding DNA fragments (ca. 150 base pairs in length) to non-cationic lipids and water. The self-assembly process often leads to highly ordered structures. The structures were studied by combining X-ray scattering, fluorescence and polarized microscopy, as well as freeze-fracture experiments with transmission electron microscopy. We observe a significant increase of the smectic order as DNA is incorporated into the water layers of the lamellar host phase, and stabilization of single phase domains for large amounts of DNA. The effect of confinement on DNA ordering is investigated by varying the water content, following three dilution lines. A rich polymorphism is found, ranging from weakly correlated DNA-DNA in-plane organizations to highly ordered structures, where transmembrane correlations lead to the formation of columnar rectangular and columnar hexagonal superlattices of nucleotides embedded between lipid lamellae. From these observations, we suggest that addition of DNA to the lamellar phase significantly restricts membrane fluctuations above a certain concentration and helps the formation of the lipoplex. The alteration of membrane steric interactions, together with the appearance of interfacial interactions between membranes and DNA molecules may be a relevant mechanism for the emergence of highly ordered structures in the concentrated regime.

On the influence of non-thermal pressure on the mass determination of galaxy clusters

Aims. Given that in most cases just thermal pressure is taken into account in the hydrostatic equilibrium equation to estimate galaxy cluster mass, the main purpose of this paper is to consider the contribution of all three non-thermal components to total mass measurements. The non-thermal pressure is composed by cosmic rays, turbulence and magnetic pressures. Methods. To estimate the thermal pressure we used public XMM-Newton archival data of five Abell clusters to derive temperature and density profiles. To describe the magnetic pressure, we assume a radial distribution for the magnetic field, B(r) proportional to rho(alpha)(g). To seek generality we assume alpha within the range of 0.5 to 0.9, as indicated by observations and numerical simulations. Turbulent motions and bulk velocities add a turbulent pressure, which is considered using an estimate from numerical simulations. For this component, we assume an isotropic pressure, P(turb) = 1/3 rho(g)(sigma(2)(r) + sigma(2)(t)). We also consider the contribution of cosmic ray pressure, P(cr) proportional to r(-0.5). Thus, besides the gas (thermal) pressure, we include these three non-thermal components in the magnetohydrostatic equilibrium equation and compare the total mass estimates with the values obtained without them. Results. A consistent description for the non-thermal component could yield a variation in mass estimates that extends from 10% to similar to 30%. We verified that in the inner parts of cool core clusters the cosmic ray component is comparable to the magnetic pressure, while in non-cool core clusters the cosmic ray component is dominant. For cool core clusters the magnetic pressure is the dominant component, contributing more than 50% of the total mass variation due to non-thermal pressure components. However, for non-cool core clusters, the major influence comes from the cosmic ray pressure that accounts for more than 80% of the total mass variation due to non-thermal pressure effects. For our sample, the maximum influence of the turbulent component to the total mass variation can be almost 20%. Although all of the assumptions agree with previous works, it is important to notice that our results rely on the specific parametrization adopted in this work. We show that this analysis can be regarded as a starting point for a more detailed and refined exploration of the influence of non-thermal pressure in the intra-cluster medium (ICM).

Determination of post-mortem interval using in situ tissue optical fluorescence

In this study we have used fluorescence spectroscopy to determine the post-mortem interval. Conventional methods in forensic medicine involve tissue or body fluids sampling and laboratory tests, which are often time demanding and may depend on expensive analysis. The presented method consists in using time-dependent variations on the fluorescence spectrum and its correlation with the time elapsed after regular metabolic activity cessation. This new approach addresses unmet needs for post-mortem interval determination in forensic medicine, by providing rapid and in situ measurements that shows improved time resolution relative to existing methods. (C) 2009 Optical Society of America

Non-Markovian dynamics of quantum discord

We evaluate the quantum discord dynamics of two qubits in independent and common non-Markovian environments. We compare the dynamics of entanglement with that of quantum discord. For independent reservoirs the quantum discord vanishes only at discrete instants whereas the entanglement can disappear during a finite time interval. For a common reservoir, quantum discord and entanglement can behave very differently with sudden birth of the former but not of the latter. Furthermore, in this case the quantum discord dynamics presents sudden changes in the derivative of its time evolution which is evidenced by the presence of kinks in its behavior at discrete instants of time.

GLOBAL WELL-POSEDNESS AND NON-LINEAR STABILITY OF PERIODIC TRAVELING WAVES FOR A SCHRODINGER-BENJAMIN-ONO SYSTEM

The objective of this paper is two-fold: firstly, we develop a local and global (in time) well-posedness theory for a system describing the motion of two fluids with different densities under capillary-gravity waves in a deep water flow (namely, a Schrodinger-Benjamin-Ono system) for low-regularity initial data in both periodic and continuous cases; secondly, a family of new periodic traveling waves for the Schrodinger-Benjamin-Ono system is given: by fixing a minimal period we obtain, via the implicit function theorem, a smooth branch of periodic solutions bifurcating a Jacobian elliptic function called dnoidal, and, moreover, we prove that all these periodic traveling waves are nonlinearly stable by perturbations with the same wavelength.

Non-Cardiac Surgery in Developing Countries: Epidemiological Aspects and Economical Opportunities - The Case of Brazil

Background: Worldwide distribution of surgical interventions is unequal. Developed countries account for the majority of surgeries and information about non-cardiac operations in developing countries is scarce. The purpose of our study was to describe the epidemiological data of non-cardiac surgeries performed in Brazil in the last years. Methods and Findings: This is a retrospective cohort study that investigated the time window from 1995 to 2007. We collected information from DATASUS, a national public health system database. The following variables were studied: number of surgeries, in-hospital expenses, blood transfusion related costs, length of stay and case fatality rates. The results were presented as sum, average and percentage. The trend analysis was performed by linear regression model. There were 32,659,513 non-cardiac surgeries performed in Brazil in thirteen years. An increment of 20.42% was observed in the number of surgeries in this period and nowadays nearly 3 million operations are performed annually. The cost of these procedures has increased tremendously in the last years. The increment of surgical cost was almost 200%. The total expenses related to surgical hospitalizations were more than $10 billion in all these years. The yearly cost of surgical procedures to public health system was more than $1.27 billion for all surgical hospitalizations, and in average, U$445.24 per surgical procedure. The total cost of blood transfusion was near $98 million in all years and annually approximately $10 million were spent in perioperative transfusion. The surgical mortality had an increment of 31.11% in the period. Actually, in 2007, the surgical mortality in Brazil was 1.77%. All the variables had a significant increment along the studied period: r square (r(2)) = 0.447 for the number of surgeries (P = 0.012), r(2) = 0.439 for in-hospital expenses (P = 0.014) and r(2) = 0.907 for surgical mortality (P = 0.0055). Conclusion: The volume of surgical procedures has increased substantially in Brazil through the past years. The expenditure related to these procedures and its mortality has also increased as the number of operations. Better planning of public health resource and strategies of investment are needed to supply the crescent demand of surgery in Brazil.

Placebo Response of Non-Pharmacological and Pharmacological Trials in Major Depression: A Systematic Review and Meta-Analysis

Background: Although meta-analyses have shown that placebo responses are large in Major Depressive Disorder (MDD) trials; the placebo response of devices such as repetitive transcranial magnetic stimulation (rTMS) has not been systematically assessed. We proposed to assess placebo responses in two categories of MDD trials: pharmacological (antidepressant drugs) and non-pharmacological (device-rTMS) trials. Methodology/Principal Findings: We performed a systematic review and meta-analysis of the literature from April 2002 to April 2008, searching MEDLINE, Cochrane, Scielo and CRISP electronic databases and reference lists from retrieved studies and conference abstracts. We used the keywords placebo and depression and escitalopram for pharmacological studies; and transcranial magnetic stimulation and depression and sham for non-pharmacological studies. All randomized, double-blinded, placebo-controlled, parallel articles on major depressive disorder were included. Forty-one studies met our inclusion criteria-29 in the rTMS arm and 12 in the escitalopram arm. We extracted the mean and standard values of depression scores in the placebo group of each study. Then, we calculated the pooled effect size for escitalopram and rTMS arm separately, using Cohen's d as the measure of effect size. We found that placebo response are large for both escitalopram (Cohen's d-random-effects model-1.48; 95% C.I. 1.26 to 1.6) and rTMS studies (0.82; 95% C.I. 0.63 to 1). Exploratory analyses show that sham response is associated with refractoriness and with the use of rTMS as an add-on therapy, but not with age, gender and sham method utilized. Conclusions/Significance: We confirmed that placebo response in MDD is large regardless of the intervention and is associated with depression refractoriness and treatment combination (add-on rTMS studies). The magnitude of the placebo response seems to be related with study population and study design rather than the intervention itself.

Role of the gp85/Trans-Sialidases in Trypanosoma cruzi Tissue Tropism: Preferential Binding of a Conserved Peptide Motif to the Vasculature In Vivo

Background: Transmitted by blood-sucking insects, the unicellular parasite Trypanosoma cruzi is the causative agent of Chagas' disease, a malady manifested in a variety of symptoms from heart disease to digestive and urinary tract dysfunctions. The reasons for such organ preference have been a matter of great interest in the field, particularly because the parasite can invade nearly every cell line and it can be found in most tissues following an infection. Among the molecular factors that contribute to virulence is a large multigene family of proteins known as gp85/trans-sialidase, which participates in cell attachment and invasion. But whether these proteins also contribute to tissue homing had not yet been investigated. Here, a combination of endothelial cell immortalization and phage display techniques has been used to investigate the role of gp85/trans-sialidase in binding to the vasculature. Methods: Bacteriophage expressing an important peptide motif (denominated FLY) common to all gp85/trans-sialidase proteins was used as a surrogate to investigate the interaction of this motif with the endothelium compartment. For that purpose phage particles were incubated with endothelial cells obtained from different organs or injected into mice intravenously and the number of phage particles bound to cells or tissues was determined. Binding of phages to intermediate filament proteins has also been studied. Findings and Conclusions: Our data indicate that FLY interacts with the endothelium in an organ-dependent manner with significantly higher avidity for the heart vasculature. Phage display results also show that FLY interaction with intermediate filament proteins is not limited to cytokeratin 18 (CK18), which may explain the wide variety of cells infected by the parasite. This is the first time that members of the intermediate filaments in general, constituted by a large group of ubiquitously expressed proteins, have been implicated in T. cruzi cell invasion and tissue homing.

Identification of protein-coding and non-coding RNA expression profiles in CD34(+) and in stromal cells in refractory anemia with ringed sideroblasts

Background: Myelodysplastic syndromes (MDS) are a group of clonal hematological disorders characterized by ineffective hematopoiesis with morphological evidence of marrow cell dysplasia resulting in peripheral blood cytopenia. Microarray technology has permitted a refined high-throughput mapping of the transcriptional activity in the human genome. Non-coding RNAs (ncRNAs) transcribed from intronic regions of genes are involved in a number of processes related to post-transcriptional control of gene expression, and in the regulation of exon-skipping and intron retention. Characterization of ncRNAs in progenitor cells and stromal cells of MDS patients could be strategic for understanding gene expression regulation in this disease. Methods: In this study, gene expression profiles of CD34(+) cells of 4 patients with MDS of refractory anemia with ringed sideroblasts (RARS) subgroup and stromal cells of 3 patients with MDS-RARS were compared with healthy individuals using 44 k combined intron-exon oligoarrays, which included probes for exons of protein-coding genes, and for non-coding RNAs transcribed from intronic regions in either the sense or antisense strands. Real-time RT-PCR was performed to confirm the expression levels of selected transcripts. Results: In CD34(+) cells of MDS-RARS patients, 216 genes were significantly differentially expressed (q-value <= 0.01) in comparison to healthy individuals, of which 65 (30%) were non-coding transcripts. In stromal cells of MDS-RARS, 12 genes were significantly differentially expressed (q-value <= 0.05) in comparison to healthy individuals, of which 3 (25%) were non-coding transcripts. Conclusions: These results demonstrated, for the first time, the differential ncRNA expression profile between MDS-RARS and healthy individuals, in CD34(+) cells and stromal cells, suggesting that ncRNAs may play an important role during the development of myelodysplastic syndromes.

Treatment of Osteomyelitis in the Feet of Diabetic Patients by Photodynamic Antimicrobial Chemotherapy

Objective: This article describes two inexpensive photodynamic antimicrobial chemotherapy (PACT) protocols to provide intensive local care on ulcerated feet of diabetic patients with osteomyelitis. Background Data: Patients with this condition generally have poor quality of life. The usual treatment consists of the administration of a cocktail of drugs including anti-inflammatories, promoters of blood circulation, and systemic antibiotics. However, depending on the conditions of the tissues, amputation may be required. Consequently, it is important to develop PACT protocols that can help avoid amputation. Materials and Methods: Two PACT protocols were applied to two diabetic patients with osteomyelitis. These protocols were based on several PACT sessions that consisted of: (1) local injection of mixtures of phenothiazines (2% in water) and Hypericum perforatum extract (10% in propylene glycol), and (2) illumination, lasting 10 min, applied to the lesion's interior and exterior using, respectively, an optical fiber and a non-coherent light source. The frequency of PACT was daily or every other day in the beginning, and weekly after tissue recovery begun. The patients were followed clinically and by radiographic testing. Results: Both PACT protocols helped cure these patients who were about to have amputation of their feet. Radiograms showed that bone had healed and that the bone's texture had improved. Conclusion: Here we have described efficient and affordable PACT protocols to treat osteomyelitis in the feet of diabetic patients. This treatment modality should be considered by vascular surgeons and by orthopedists to treat osteomyelitis that is resistant to conventional treatments.

Nitrogen availability patterns in white-sand vegetations of Central Brazilian Amazon

Addressing spatial variability in nitrogen (N) availability in the Central Brazilian Amazon, we hypothesized that N availability varies among white-sand vegetation types (campina and campinarana) and lowland tropical forests (dense terra-firme forests) in the Central Brazilian Amazon, under the same climate conditions. Accordingly, we measured soil and foliar N concentration and N isotope ratios (delta(15)N) throughout the campina-campinarana transect and compared to published dense terra-firme forest results. There were no differences between white-sand vegetation types in regard to soil N concentration, C:N ratio and delta(15)N across the transect. Both white-sand vegetation types showed very low foliar N concentrations and elevated foliar C:N ratios, and no significant difference between site types was observed. Foliar delta(15)N was depleted, varying from -9.6 to 1.6aEuro degrees in the white-sand vegetations. The legume Aldina heterophylla had the highest average delta(15)N values (-1.5aEuro degrees) as well as the highest foliar N concentration (2.1%) while the non-legume species had more depleted delta(15)N values and the average foliar N concentrations varied from 0.9 to 1.5% among them. Despite the high variation in foliar delta(15)N among plants, a significant and gradual (15)N-enrichment in foliar isotopic signatures throughout the campina-campinarana transect was observed. Individual plants growing in the campinarana were significantly enriched in (15)N compared to those in campina. In the white-sand N-limited ecosystems, the differentiation of N use seems to be a major cause of variations observed in foliar delta(15)N values throughout the campina-campinarana transect.