Chagas disease in a recipient of cord blood transplantation.
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Adult↗
Biomedical subjects
S Gil
Publications and source records attributed to S Gil.
Formulation in tablets of a cholera whole cells inactivated vaccine candidate.
Licensed as well as candidate cholera vaccines available at the present requires the dose preparation (included buffer) at the moment of application. The aim of this work was to evaluate the presentation in oral tablets of an inactivated cholera vaccine to avoid that inconveniences during application. We have therefore compared inactivated cultures of Vibrio cholerae with tablets formulation vaccine. We obtained that antigenic activity (ELISA) and immunogenicity in animal model (ELISA and vibriocidal tests) of V. cholerae inactivated cell remained unaltered in the final tablet formulation. The results suggest that the oral tablet formulation could be a useful pharmaceutical form in order to produce a new and affordable cholera vaccine.
Administration, Oral↗
Conservative treatment with transurethral resection, neoadjuvant chemotherapy followed by radiochemotherapy in stage T2-3 transitional bladder cancer.
PURPOSE: Organ preservation has been investigated in patients (p) with infiltrating transitional cell carcinoma (TCC) of the bladder over the past decade as an alternative to radical cystectomy. This is a trimodal schedule study, including transurethral resection of bladder tumor (TURB), neoadjuvant chemotherapy and concomitant radiochemotherapy (RTC). PATIENTS AND METHODS: From April 1996 until August 2005, 29 evaluable patients (p) with T2-T3NXM0 bladder cancer were enrolled. After a transurethral resection of bladder tumor (TURB), we administered 2 cycles of induction chemotherapy with CMV (15 p) or Gemcitabine-Cisplatin (14 p) followed by radiotherapy 45 Gy 1.8 Gy/fraction and two cycles of concomitant cisplatin 70 mg/m(2). 2-3 weeks later, a cystoscopy with tumor-site biopsy was performed. If complete histological response, p were treated with consolidation radiotherapy until 64.8 Gy. For p with residual or recurrent tumor, cystectomy was performed. RESULTS: We included 28 men and 1 women (median age 63, range 39-72 years) with PS (ECOG) 0-1. The stage was: 21 p T2; 6 p T3a; and 2 p T3b. Toxicity was higher in CMV compared with Gem- Cis: grade (3/4) neutropenia 4/15 (26%) vs 1/14 (7%); febrile neutropenia 3/15 (20%) vs 1/14 (7%); grade (3/4) trombocytopenia 2/15 (13%) vs 1/14 (7%). Toxicities with concomitant RCT were low-moderate: urocystitis (26%) and enteritis (18%). RESPONSE: microscopically complete TURB was obtained in 20 p (69%), but not in 9 p (31%) (7 microscopic, and 2 macroscopic residual tumor). We found a complete histologic response after induction RCT in 25 p (86%). After a median follow-up of 69.4 months (m) (range: 8-97.7), there were 8 deaths, with a overall survival of 72%. Furthermore 14 of 29 p (48%) were alive with intact bladder, and median survival time with intact bladder was 63.6 m (50.1-77.2); were predictive of best outcome T2 stage vs T3 (p < 0.0001), and complete histologic resection in initial TURB vs residual tumor (p = 0.0004). CONCLUSIONS: Combined treatment provide high response rates and can be offered as an alternative option to radical cystectomy in selected patients with TCC. Patients with T2 stage and complete histologic resection in initial TURB had the best outcome.
Adult↗
Anaesthetic management of acute myocardial infarction during labour.
Coronary artery disease is rarely detected during labour and the puerperium. We report the case of a 31-year-old primigravida at 38 weeks of gestation with hypercholesterolaemia and a family history of coronary heart disease, who presented with septal acute myocardial infarction. We decided to perform a caesarean section under general anaesthesia. The patient was later admitted to the intensive care unit. There were no complications during or after surgery. Cardiac ultrasound showed septal hypokinesia with normal systolic function and coronary angiography revealed normal coronary vessels. She remained haemodynamically stable and was discharged from intensive care 48 h later.
Adult↗
Overexpression of dopamine receptor genes and their products in the postnatal rat brain following maternal n-3 fatty acid dietary deficiency.
A combination of PCR-Select cDNA subtraction and gene array hybridization was used to identify differentially expressed genomic markers in brains of rats fed for 3 weeks in utero and 2 weeks after birth on an n-3 polyunsaturated fatty acid (PUFA)-deficient diet supplied to dams. Total RNA was isolated, switch mechanism at 5'-end of the RNA transcripts (SMART) applied and used for PCR-Select subtraction of PUFA-deficient and adequately-fed control preparations. Subtracted and amplified ds-cDNA end-products were fragmented, terminally labeled with biotin-ddUTP and hybridized with a RN-U34A gene array. A 10-fold increase in potential genes with log2(Tester/Driver) = 1.4 was found compared with traditional gene array technology when the same chip was tested using non-subtracted targets. Reverse transcription-real-time relative PCR confirmed 30% of the transcripts. Among the validated transcripts, D1 and D2 receptors for dopamine (DA), were most prominent among a number of over-expressed neurotransmitter receptors and retinoic acid receptor (RXR alpha-2 and alpha-1). Immunohistochemical staining of brain sections from 2-week-old pups revealed a substantial enrichment of the D2 receptor in discrete regions of the mesolimbic and mesocortical pathways as well as in a large number of brain areas from the n-3 PUFA-deficient pups. Punches of the same areas run on western blots showed similar results. The overwhelming expression of D1 and D2 receptors may be attributed to a behavioral hypersensitivity caused by the possible impairment of DA production during brain development, which may have implications in certain disorders of the nervous system.
Animals↗
Increased expression of MDR1 mRNAs and P-glycoprotein in placentas from HIV-1 infected women.
P-glycoprotein transports several compounds including protease inhibitors, actually used in the clinical management of HIV-1 infection. Since P-glycoprotein is expressed in placental trophoblasts, its efflux activity could interfere with placental transfer of antiretrovirals. The purpose of this study was to investigate the expression of P-gp-encoding MDR1 gene and P-gp itself in full-term placentas from uninfected (n=35) and HIV-1 infected women (n=24). MDR1 transcripts were quantified by real-time PCR using relative (MDR1 normalized upon 28S levels) and absolute (copy number) determinations. P-glycoprotein localization and expression were evaluated by immunohistochemistry and western blot analysis, respectively. Relative or absolute PCR quantification showed a significant 3.3-fold (p<0.0009) or 3.7-fold (p<0.0002) mean increase in MDR1 placental transcription in HIV-infected compared to non-infected women, respectively. Ratios of individual HIV-positive values to HIV-negative mean ranged from 0.1 to 21.8. Moreover a significant 2.5-fold increased expression of immunoreactive P-glycoprotein was evidenced in placentas from HIV-infected women (p<0.0001). This MDR1 overexpression was observed in a similar extent in placentas from pregnant women treated with Zidovudine alone or in combination with Nelfinavir and/or Lamivudine. Our findings suggest that P-glycoprotein in placentas from HIV-infected women would contribute to modulate the materno-fetal transport of antiretrovirals across the placental barrier and consequently diminish fetal exposure to these compounds.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Process development for a Cuban cholera vaccine based on the attenuated strain Vibrio cholerae 638.
Genetically modified Vibrio cholerae strain 638 (biotype El Tor, serotype Ogawa) has previously been shown to be immunogenic in animal models and in human trials. Our objective in the work reported herein was to describe the process development methods for the production of the 638 attenuated cholera vaccine. Cell seed bank, culture of biomass, lyophilization and final formulation were processes were developed. The results show kinetics of culture that fulfils a logistical model. The microbiological properties, colonizing capability, immunogenicity and non-toxigenicity of the final product were indistinguishable from the properties of the working seed lot. We conclude that the non-reactogenic, immunogenic and protective strain 638 is robust and can withstand the fermentation processes required for large-scale production of a vaccine.
Animals↗
Colloidal carriers and blood-brain barrier (BBB) translocation: a way to deliver drugs to the brain?
The major problem in drug delivery to the brain is the presence of the blood-brain barrier (BBB) which limits drug penetration even if in certain pathological situations the BBB is partly disrupted. Therefore, various strategies have been proposed to improve the delivery of drugs to this tissue. This review presents the status of the BBB in healthy patients and in pathologies like neurodegenerative, cerebrovascular and inflammatory diseases. The second part of this article aims to review the invasive and non-invasive strategies developed to circumvent the BBB and deliver drugs into the brain. The use of nanotechnologies (liposomes, nanoparticles) is especially discussed in the ultimate part of the review evidencing their potentiality as non-invasive technique in the brain delivery of drugs with the possibility to target specific brain tissue thanks to ligand linked to carrier surface.
Animals↗
A relevant in vitro rat model for the evaluation of blood-brain barrier translocation of nanoparticles.
Poly(MePEG2000cyanoacrylate-co-hexadecylcyanoacrylate) (PEG-PHDCA) nanoparticles have demonstrated their capacity to reach the rat central nervous system after intravenous injection. For insight into the transport of colloidal systems across the blood-brain barrier (BBB), we developed a relevant in vitro rat BBB model consisting of a coculture of rat brain endothelial cells (RBECs) and rat astrocytes. The RBECs used in our model displayed and retained structural characteristics of brain endothelial cells, such as expression of P-glycoprotein, occludin and ZO-1, and immunofluorescence studies showed the specific localization of occludin and ZO1. The high values of transendothelial electrical resistance and low permeability coefficients of marker molecules demonstrated the functionality of this model. The comparative passage of polyhexadecylcyanoacrylate and PEG-PHDCA nanoparticles through this model was investigated, showing a higher passage of PEGylated nanoparticles, presumably by endocytosis. This result was confirmed by confocal microscopy. Thanks to a good in vitro/in vivo correlation, this rat BBB model will help in understanding the mechanisms of nanoparticle translocation and in designing new types of colloidal carriers as brain delivery systems.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
[Management of anesthesia in a pregnant woman with severe aortic stenosis and von Willebrand's disease].
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Adult↗
Overexpression of genes in the CA1 hippocampus region of adult rat following episodes of global ischemia.
Ischemic stress is associated with marked changes in gene expression in the hippocampus--albeit little information exists on the activation of nonabundant genes. We have examined the expression of several known genes and identified novel ones in the adult rat hippocampus after a mild, transient, hypovolemic and hypotensive, global ischemic stress. An initial differential screening using a prototype array to assess gene expression after stress followed by a suppression subtractive hybridization protocol and cDNA microarray revealed 124 nonoverlapped transcripts predominantly expressed in the CA1 rat hippocampus region in response to ischemic stress. About 78% of these genes were not detected with nonsubtracted probes. Reverse transcription polymerase chain reaction (RT-PCR) and in situ hybridization on these 124 transcripts confirmed the differential expression of at least 83. Most robustly expressed were gene sequences NFI-B, ATP1B1, RHOGAP, PLA2G4A, BAX, CASP3, P53, MAO-A, FRA1, HSP70.2, and NR4A1 (NUR77), as well as sequence tags of unknown function. New stress-related genes of similar functional motifs were identified, reemphasizing the importance of functional grouping in the analysis of multiple gene expression profiles. These data indicate that ischemia elicits expression of an array of functional gene clusters that may be used as an index for stress severity and a template for target therapy design.
Animals↗
False-positive amniotic fluid acetylcholinesterase PAGE due to contamination by the AFP diluent of an automated instrument.
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Acetylcholinesterase↗
Utilizing Solanum glaucophyllum alone or with phytase to improve phosphorus utilization in broilers.
Experiments were conducted to determine if Solanum glaucophyllum (SG), a plant containing a glycoside of 1,25-dihydroxyvitamin D, could be used as a feed additive to improve P utilization of broilers. SG leaves (1, 2.5, or 5 g/kg), 1,25-dihydroxyvitamin D (15 microg/kg), or Ca and P (to achieve a 0.92% Ca:0.65% P:0.41% nonphytate P control diet) were added to a 0.56% Ca/0.45% P/0.28% nonphytate P basal diet and fed to broilers from 7 to 28 d of age. Birds fed basal ration alone exhibited reduced weight gain, bone density, and bone mineral content when compared with birds fed the 0.92% Ca:0.65% P diet. Adding 5 g SG leaves or 15 microg of 1,25-dihydroxyvitamin D/kg to the basal diet increased body weight gain, plasma Ca and P, bone ash, and bone density above basal diet levels. Plasma P and weight gain of birds fed 5 g SG or 15 microg of 1,25-dihydroxyvitamin D/kg basal diet were equivalent to those observed in birds fed the 0.92% Ca:0.65% P diet. In experiment 2, the effect of higher doses of SG, as well as the additive effect of SG with 1,200 phytase units/kg diet, were examined in chicks fed a 0.59% Ca and 0.42% P basal diet. Two levels of SG leaves (7.5 g and 10 g), phytase, or both SG (7.5 g) and phytase were added per kilogram of basal diet. Adding SG or phytase to the basal diet increased weight gain, plasma Ca, plasma P, and bone mineral content over that observed in birds fed basal diet alone. Combining SG with phytase provided no significant gains in growth or bone parameters over treatment with phytase alone.
6-Phytase↗
Expression at mRNA level of cytokines and A238L gene in porcine blood-derived macrophages infected in vitro with African swine fever virus (ASFV) isolates of different virulence.
Porcine macrophage cultures were infected with two ASFV isolates of variable virulence and mRNA levels of several relevant macrophage-derived cytokines were quantified by real time PCR. At six hours post infection, a clear enhancement of mRNA expression of TNFalpha, IL6, IL12 and IL15 was observed in macrophages infected with the low virulent ASFV/NH/P68 (NHV) when compared to those infected with the highly virulent ASFV/L60 (L60). The sequence of the A238L gene homologue to the cellular IkappaB was found identical in both viral isolates and its expression at mRNA level was higher in macrophages infected with NHV when compared to macrophages infected with L60. Furthermore our results suggest a negative correlation between the mRNA expression of A238L gene and the mRNA expression of the above mentioned cytokines (with the exception of IL10) in L60 infected macrophages in opposition to the positive correlation (with exception of the IL1) suggested in NHV infection. Overall, our data strongly emphasize that virulence of ASFV isolates may depend on their capacity to regulate the expression of macrophage-derived cytokines relevant for the development of host protective responses by yet unknown mechanisms triggered by the virus at early stages of the cellular infection.
African Swine Fever↗
Direct evidence for neutrino flavor transformation from neutral-current interactions in the Sudbury Neutrino Observatory.
Observations of neutral-current nu interactions on deuterium in the Sudbury Neutrino Observatory are reported. Using the neutral current (NC), elastic scattering, and charged current reactions and assuming the standard 8B shape, the nu(e) component of the 8B solar flux is phis(e) = 1.76(+0.05)(-0.05)(stat)(+0.09)(-0.09)(syst) x 10(6) cm(-2) s(-1) for a kinetic energy threshold of 5 MeV. The non-nu(e) component is phi(mu)(tau) = 3.41(+0.45)(-0.45)(stat)(+0.48)(-0.45)(syst) x 10(6) cm(-2) s(-1), 5.3sigma greater than zero, providing strong evidence for solar nu(e) flavor transformation. The total flux measured with the NC reaction is phi(NC) = 5.09(+0.44)(-0.43)(stat)(+0.46)(-0.43)(syst) x 10(6) cm(-2) s(-1), consistent with solar models.
Journal Article↗
Measurement of day and night neutrino energy spectra at SNO and constraints on neutrino mixing parameters.
The Sudbury Neutrino Observatory (SNO) has measured day and night solar neutrino energy spectra and rates. For charged current events, assuming an undistorted 8B spectrum, the night minus day rate is 14.0%+/-6.3%(+1.5%)(-1.4%) of the average rate. If the total flux of active neutrinos is additionally constrained to have no asymmetry, the nu(e) asymmetry is found to be 7.0%+/-4.9%(+1.3%)(-1.2%). A global solar neutrino analysis in terms of matter-enhanced oscillations of two active flavors strongly favors the large mixing angle solution.
Journal Article↗
Measurement of the rate of nu(e) + d --> p + p + e(-) interactions produced by (8)B solar neutrinos at the Sudbury Neutrino Observatory.
Solar neutrinos from (8)B decay have been detected at the Sudbury Neutrino Observatory via the charged current (CC) reaction on deuterium and the elastic scattering (ES) of electrons. The flux of nu(e)'s is measured by the CC reaction rate to be straight phi(CC)(nu(e)) = 1.75 +/- 0.07(stat)(+0.12)(-0.11)(syst) +/- 0.05(theor) x 10(6) cm(-2) s(-1). Comparison of straight phi(CC)(nu(e)) to the Super-Kamiokande Collaboration's precision value of the flux inferred from the ES reaction yields a 3.3 sigma difference, assuming the systematic uncertainties are normally distributed, providing evidence of an active non- nu(e) component in the solar flux. The total flux of active 8B neutrinos is determined to be 5.44+/-0.99 x 10(6) cm(-2) s(-1).
Journal Article↗
Lipid constituents in oligodendroglial cells alter susceptibility to H2O2-induced apoptotic cell death via ERK activation.
The present work examines the effect of membrane lipid composition on activation of extracellular signal-regulated protein kinases (ERK) and cell death following oxidative stress. When subjected to 50 microM docosahexaenoic acid (DHA, 22 : 6 n-3), cellular phospholipids of OLN 93 cells, a clonal line of oligodendroglia origin low in DHA, were enriched with this polyunsaturated fatty acid. In the presence of 1 mM N,N-dimethylethanolamine (dEa) a new phospholipid species analog was formed in lieu of phosphatidylcholine. Exposure of DHA-enriched cells to 0.5 mM H2O2, caused sustained activation of ERK up to 24 h. At this time massive apoptotic cell death was demonstrated by ladder and TUNEL techniques. H2O2-induced stress applied to dEa or DHA/dEa co-supplemented cells showed only a transient ERK activation and no cell death after 24 h. Moreover, while ERK was rapidly translocated into the nucleus in DHA-enriched cells, dEa supplements completely blocked ERK nuclear translocation. This study suggests that H2O2-induced apoptotic cell death is associated with prolonged ERK activation and nuclear translocation in DHA-enriched OLN 93 cells, while both phenomena are prevented by dEa supplements. Thus, the membrane lipid composition ultimately modulates ERK activation and translocation and therefore can promote or prevent apoptotic cell death.
Apoptosis↗