Simultaneous quantitation of serum HBV DNA and HBeAg can distinguish between slow and fast viral responses to antiviral therapy in patients with chronic hepatitis B

BACKGROUND: The quantitation of serum HBeAg is not commonly used to monitor viral response to therapy in chronic hepatitis B. METHODS: In this study, 21 patients receiving varying therapies were followed and their viral response monitored by concomitant viral load and HBeAg quantitation in order to study the meaning and the kinetics of both parameters. RESULTS: It was possible to distinguish between three different patterns of viral response. The first was characterized by a simultaneous decrease in serum HBV DNA and HBeAg. The second pattern was characterized by a decrease in serum HBeAg but persistent detection of HBV DNA. The third pattern was characterized by undetectable HBV DNA with persistent HBeAg positivity, which points to a non-response (Pattern III-B) except when HBeAg levels showed a slow but steady drop, characterizing a "slow responder" patient (Pattern III-A). CONCLUSIONS: The first pattern is compatible with a viral response. A long-term HBeAg seropositivity with a slow and persistent decrease (Pattern III-A) is also compatible with a viral response and calls for a prolongation of anti-viral treatment.

High prevalence of the simultaneous excretion of polyomaviruses JC and BK in the urine of HIV-infected patients without neurological symptoms in São Paulo, Brazil

OBJECTIVE: To evaluate the prevalence of the urinary excretion of BKV and JCV in HIV-infected patients without neurological symptoms. METHODS: Urine samples from HIV-infected patients without neurological symptoms were tested for JC virus and BK virus by PCR. Samples were screened for the presence of polyomavirus with sets of primers complementary to the early region of JCV and BKV genome (AgT). The presence of JC virus or BK virus were confirmed by two other PCR assays using sets of primers complementary to the VP1 gene of each virus. Analysis of the data was performed by the Kruskal-Wallis test for numerical data and Pearson or Yates for categorical variables. RESULTS: A total of 75 patients were included in the study. The overall prevalence of polyomavirus DNA urinary shedding was 67/75 (89.3%). Only BKV DNA was detected in 14/75 (18.7%) urine samples, and only JCV DNA was detected in 11/75 (14.7%) samples. Both BKV and JCV DNA were present in 42/75 (56.0%) samples. CONCLUSION: In this study we found high rates of excretion of JCV, BKV, and simultaneous excretion in HIV+ patients. Also these results differ from the others available on the literature.

Stochastic modeling of the thermal and catalytic degradation of polyethylene using simultaneous DSC/TG analysis

Dissertação para obtenção do Grau de Mestre em Engenharia Química e Bioquímica

Simultaneous occurrence of pulmonary tuberculosis and carcinomatous lymphangitis

Tuberculosis is an important cause of mortality due to its high prevalence, considering that one third of the world’s population is infected with the tuberculosis bacillus. We report the first case of carcinomatous lymphangitis associated with active pulmonary tuberculosis. Carcinomatous lymphangitis is a rare event that may be confounded with tuberculosis because of its radiographic and clinical characteristics.

Simultaneous occurrence of brain tumor and myeloradiculopathy in schistosomiasis mansoni: case report

Simultaneous occurrence of brain tumor and myeloradiculopathy in cases of Manson's schistosomiasis have only rarely been described. We report the case of a 38-year-old man who developed seizures during a trip to Puerto Rico and in whom a brain tumor was diagnosed by magnetic resonance imaging: brain biopsy revealed the diagnosis of schistosomiasis. He was transferred to a hospital in the United States and, during hospitalization, he developed sudden paraplegia. The diagnosis of myeloradiculopathy was confirmed at that time. He was administered praziquantel and steroids. The brain tumor disappeared, but the patient was left with paraplegia and fecal and urinary dysfunction. He has now been followed up in Brazil for one year, and his clinical state, imaging examinations and laboratory tests are presented here.

Simultaneous circulation of all four dengue serotypes in Manaus, State of Amazonas, Brazil in 2011

INTRODUCTION: Manaus, the capital city of the state of Amazon with nearly 2 million inhabitants, is located in the middle of the Amazon rain forest and has suffered dengue outbreaks since 1998. METHODS: In this study, blood samples were investigated using reverse transcriptase-polymerase chain reaction (RT-PCR), aimed at identifying dengue virus serotypes. RESULTS: Acute phase sera from 432 patients were tested for the presence of dengue virus. Out of the 432 patients, 137 (31.3%) were found to be positive. All the four dengue virus serotypes were observed. CONCLUSIONS: The simultaneous circulation of the four dengue serotypes is described for the first time in Manaus and in Brazil.

Exploring the potentialities of a new type of CFRP laminate for the simultaneous flexural and shear strengthening of RC beams: numerical research

This study aims to develop an innovative carbon fibre reinforced polymer (CFRP) laminate with a U configuration to address strengthening interventions, where the increment of both flexural and shear capacity of reinforced concrete (RC) elements is required. This strengthening solution combines the near surface mounted (NSM) and embedded through section (ETS) techniques in the same application, since these techniques have already evidenced high performance on flexural and shear strengthening of RC beams using FRP systems, respectively. In fact, the proposed hybrid technique aims to mobilize the advantages provided by these two strengthening techniques by using an innovative CFRP laminate. The strengthening efficacy of this new hybrid NSM/ETS technique was numerically assessed and compared to the corresponding efficiency of NSM and ETS techniques applied separately for the flexural and shear strengthening of RC beams, respectively. The numerical models are described and the main relevant results are presented and discussed.

Simultaneous measurements of the tt¯, W+W−, and Z/γ∗→ττ production cross-sections in pp collisions at s√=7 TeV with the ATLAS detector

Simultaneous measurements of the tt¯, W+W−, and Z/γ∗→ττ production cross-sections using an integrated luminosity of 4.6 fb−1 of pp collisions at s√=7 TeV collected by the ATLAS detector at the LHC are presented. Events are selected with two high transverse momentum leptons consisting of an oppositely charged electron and muon pair. The three processes are separated using the distributions of the missing transverse momentum of events with zero and greater than zero jet multiplicities. Measurements of the fiducial cross-section are presented along with results that quantify for the first time the underlying correlations in the predicted and measured cross-sections due to proton parton distribution functions. These results indicate that the correlated NLO predictions for tt¯ and Z/γ∗→ττ significantly underestimate the data, while those at NNLO generally describe the data well. The full cross-sections are measured to be σ(tt¯)=181.2±2.8+9.7−9.5±3.3±3.3 pb, σ(W+W−)=53.3±2.7+7.3−8.0±1.0±0.5 pb, and σ(Z/γ∗→ττ)=1174±24+72−87±21±9 pb, where the cited uncertainties are due to statistics, systematic effects, luminosity and the LHC beam energy measurement, respectively.

On line pre-concentration for simultaneous determination of low molecular weight organic acids and inorganic anions in Amazonian river water samples employing ion chromatography with conductivity detection

An ion chromatography procedure, employing an IonPac AC15 concentrator column was used to investigate on line preconcentration for the simultaneous determination of inorganic anions and organic acids in river water. Twelve organic acids and nine inorganic anions were separated without any interference from other compounds and carry-over problems between samples. The injection loop was replaced by a Dionex AC15 concentrator column. The proposed procedure employed an auto-sampler that injected 1.5 ml of sample into a KOH mobile phase, generated by an Eluent Generator, at 1.5 mL min-1, which carried the sample to the chromatographic columns (one guard column, model AG-15, and one analytical column, model AS15, with 250 x 4mm i.d.). The gradient elution concentrations consisted of a 10.0 mmol l-1 KOH solution from 0 to 6.5 min, gradually increased to 45.0 mmol l-1 KOH at 21 min., and immediatelly returned and maintained at the initial concentrations until 24 min. of total run. The compounds were eluted and transported to an electro-conductivity detection cell that was attached to an electrochemical detector. The advantage of using concentrator column was the capability of performing routine simultaneous determinations for ions from 0.01 to 1.0 mg l-1 organic acids (acetate, propionic acid, formic acid, butyric acid, glycolic acid, pyruvate, tartaric acid, phthalic acid, methanesulfonic acid, valeric acid, maleic acid, oxalic acid, chlorate and citric acid) and 0.01 to 5.0 mg l-1 inorganic anions (fluoride, chloride, nitrite, nitrate, bromide, sulfate and phosphate), without extensive sample pretreatment and with an analysis time of only 24 minutes.

Simultaneous detection of cyclopiazonic acid and aflatoxin B1 by HPLC in methanol/water mobile phase

A simple procedure for the simultaneous detection of cyclopiazonic acid (CPA) and aflatoxin B1 from fungal extracts is presented, using a methanol and water mobile phase and fluorescence detection. This methodology has been tested with standard solutions of both mycotoxins CPA and Aflatoxin B1 and with methanolic extracts of Aspergillus section Flavi strains, previously characterized for their mycotoxin production profile. Previously available methodology required the use of two different chromatographic runs for these mycotoxins, with distinct columns and detectors (fluorescence detection with a post-column photochemical derivatization (PHRED) for aflatoxin B1 and UV detection for CPA). The proposed method detects both mycotoxins in a single run. Data from these assays will be presented and discussed.

Treatment of atrial fibrillation with radiofrequency ablation and simultaneous multipolar mapping of the pulmonary veins

OBJECTIVE: To demonstrate the feasibility and safety of simultaneous catheterization and mapping of the 4 pulmonary veins for ablation of atrial fibrillation. METHODS: Ten patients, 8 with paroxysmal atrial fibrillation and 2 with persistent atrial fibrillation, refractory to at least 2 antiarrhythmic drugs and without structural cardiopathy, were consecutively studied. Through the transseptal insertion of 2 long sheaths, 4 pulmonary veins were simultaneously catheterized with octapolar microcatheters. After identification of arrhythmogenic foci radiofrequency was applied under angiographic or ultrasonographic control. RESULTS: During 17 procedures, 40 pulmonary veins were mapped, 16 of which had local ectopic activity, related or not with the triggering of atrial fibrillation paroxysms. At the end of each procedure, suppression of arrhythmias was obtained in 8 patients, and elimination of pulmonary vein potentials was accomplished in 4. During the clinical follow-up of 9.6±3 months, 7 patients remained in sinus rhythm, 5 of whom were using antiarrhythmic drugs that had previously been ineffective. None of the patients had pulmonary hypertension or evidence of stenosis in the pulmonary veins. CONCLUSION: Selective and simultaneous catheterization of the 4 pulmonary veins with microcatheters for simultaneous recording of their electrical activity is a feasible and safe procedure that may help ablation of atrial fibrillation.

Simultaneous recording of EEG and fMRI : new approach to remove gradient and ballistocardiogram EEG-artifacts

Magdeburg, Univ., Fak. für Naturwiss., Diss., 2009

Mutational analysis of the highly conserved arginine within the Glu/Asp-Arg-Tyr motif of the alpha(1b)-adrenergic receptor: effects on receptor isomerization and activation.

We have suggested previously that both the negatively and positively charged residues of the highly conserved Glu/Asp-Arg-Tyr (E/DRY) motif play an important role in the activation process of the alpha(1b)-adreneric receptor (AR). In this study, R143 of the E/DRY sequence in the alpha(1b)-AR was mutated into several amino acids (Lys, His, Glu, Asp, Ala, Asn, and Ile). The charge-conserving mutation of R143 into lysine not only preserved the maximal agonist-induced response of the alpha(1b)-AR, but it also conferred high degree of constitutive activity to the receptor. Both basal and agonist-induced phosphorylation levels were significantly increased for the R143K mutant compared with those of the wild-type receptor. Other substitutions of R143 resulted in receptor mutants with either a small increase in constitutive activity (R143H and R143D), impairment (R143H, R143D), or complete loss of receptor-mediated response (R143E, R143A, R143N, R143I). The R413E mutant displayed a small, but significant increase in basal phosphorylation despite being severely impaired in receptor-mediated response. Interestingly, all the arginine mutants displayed increased affinity for agonist binding compared with the wild-type alpha(1b)-AR. A correlation was found between the extent of the affinity shift and the intrinsic activity of the agonists. The analysis of the receptor mutants using the allosteric ternary complex model in conjunction with the results of molecular dynamics simulations on the receptor models support the hypothesis that mutations of R143 can drive the isomerization of the alpha(1b)-AR into different states, highlighting the crucial role of this residue in the activation process of the receptor.

Simultaneous LC-MS/MS quantification of P-glycoprotein and cytochrome P450 probe substrates and their metabolites in DBS and plasma.

BACKGROUND: An LC-MS/MS method has been developed for the simultaneous quantification of P-glycoprotein (P-gp) and cytochrome P450 (CYP) probe substrates and their Phase I metabolites in DBS and plasma. P-gp (fexofenadine) and CYP-specific substrates (caffeine for CYP1A2, bupropion for CYP2B6, flurbiprofen for CYP2C9, omeprazole for CYP2C19, dextromethorphan for CYP2D6 and midazolam for CYP3A4) and their metabolites were extracted from DBS (10 µl) using methanol. Analytes were separated on a reversed-phase LC column followed by SRM detection within a 6 min run time. RESULTS: The method was fully validated over the expected clinical concentration range for all substances tested, in both DBS and plasma. The method has been successfully applied to a PK study where healthy male volunteers received a low dose cocktail of the here described P-gp and CYP probes. Good correlation was observed between capillary DBS and venous plasma drug concentrations. CONCLUSION: Due to its low-invasiveness, simple sample collection and minimal sample preparation, DBS represents a suitable method to simultaneously monitor in vivo activities of P-gp and CYP.

Simultaneous CD8+ T cell responses to multiple tumor antigen epitopes in a multipeptide melanoma vaccine.

The recent identification and molecular characterization of tumor-associated antigens recognized by tumor-reactive CD8+ T lymphocytes has led to the development of antigen-specific immunotherapy of cancer. Among other approaches, clinical studies have been initiated to assess the in vivo immunogenicity of tumor antigen-derived peptides in cancer patients. In this study, we have analyzed the CD8+ T cell response of an ocular melanoma patient to a vaccine composed of four different tumor antigen-derived peptides administered simultaneously in incomplete Freund's adjuvant (IFA). Peptide NY-ESO-1(157-165) was remarkably immunogenic and induced a CD8+ T cell response detectable ex vivo at an early time point of the vaccination protocol. A CD8+ T cell response to the peptide analog Melan-A(26-35 A27L) was also detectable ex vivo at a later time point, whereas CD8+ T cells specific for peptide tyrosinase(368-376) were detected only after in vitro peptide stimulation. No detectable CD8+ T cell response to peptide gp100(457-466) was observed. Vaccine-induced CD8+ T cell responses declined rapidly after the initial response but increased again after further peptide injections. In addition, tumor antigen-specific CD8+ T cells were isolated from a vaccine injection site biopsy sample. Importantly, vaccine-induced CD8+ T cells specifically lysed tumor cells expressing the corresponding antigen. Together, these data demonstrate that simultaneous immunization with multiple tumor antigen-derived peptides can result in the elicitation of multiepitope-directed CD8+ T cell responses that are reactive against antigen-expressing tumors and able to infiltrate antigen-containing peripheral sites.