RESUMO
Unfortunately, M. M. Vrvic name has been published incorrectly in the original publication as M. M. Vrivic, corrected name appears in this erratum.
RESUMO
Despite the effectiveness of HAART in controlling HIV-1 replication, the emergence of drug-resistant viruses in infected patients and the severe side effects caused by the currently used drug regimens and the lack of an effective vaccine necessitate the continued search for new therapeutic strategies for prevention and therapy of HIV disease. Previously we reported that natural autoantibodies, recognizing peptide FTDNAKTI (peptide NTM1) derived from the C2 domain of HIV-1 gp120, contribute to the control of HIV disease. Here we demonstrated that sera from well-trained athletic (HIV-negative) subjects showed high reactivity with peptide NTM1. This result confirms that aerobic exercise training stimulates production of natural autoantibodies, which recognize peptide NTM1. Bioinformatics analysis indicates that these natural autoantibodies could slow down disease progression by blocking the superantigenic site on HIV-1 gp120. The results suggest that aerobic exercise training may be a promising non-toxic and inexpensive adjunctive anti-HIV therapy.
Assuntos
Anticorpos Neutralizantes/imunologia , Exercício Físico/fisiologia , HIV-1/imunologia , Adolescente , Anticorpos Neutralizantes/sangue , Atletas , Autoimunidade/fisiologia , Proteína gp120 do Envelope de HIV/imunologia , Humanos , Fragmentos de Peptídeos/imunologia , SérviaRESUMO
The present study was aimed to removal of Cu(II) ions from aqueous solution by ultrasound-assisted adsorption onto the granular activated carbon obtained from hazelnut shells. The attention was focused on modeling the equilibrium and kinetics of Cu(II) adsorption onto the granular activated carbon. The granular activated carbon was prepared from ground dried hazelnut shells by simultaneous carbonization and activation by water steam at 950 degrees C for 2h. Adsorption isotherm data were better fitted by the Langmuir model than the Freundlich model in both the absence and the presence of ultrasound. The maximum adsorption capacity of the adsorbent for Cu(II), calculated from the Langmuir isotherms, in the presence of ultrasound (3.77 mmol/g) is greater than that in the absence of ultrasound (3.14 mmol/g). The adsorption process in the absence and the presence of ultrasound obeyed to the pseudo second-order kinetics. The removal of Cu(II) ions was higher in the presence of ultrasound than in its absence, but ultrasound reduced the rate constant. The intraparticular diffusion model indicated that adsorption of Cu(II) ions on the granular activated carbon was diffusion controlled as well as that ultrasound promoted intraparticular diffusion.
Assuntos
Carbono/química , Cobre/química , Corylus/química , Ultrassom , Adsorção , Agricultura , Cátions/química , Corylus/anatomia & histologia , Cinética , Eliminação de ResíduosRESUMO
The development of a new therapeutic drug is a complex, lengthy and expensive process. On average, only one out of 10,000 - 30,000 originally synthesized compounds will clear all the hurdles on the way to becoming a commercially available drug. The process of early and full preclinical discovery and clinical development for a new drug can take twelve to fifteen years to complete, and cost approximately 800 million dollars. The field of bioinformatics has become a major part of the drug discovery pipeline playing a key role in improvement and acceleration of this time and money consuming process. Here we reviewed the application of the EIIP/ISM bioinformatics concept for the development of new drugs. This approach, connecting the electron-ion interaction potential of organic molecules and their biological properties, can significantly reduce development time through (i) identification of promising lead compounds that have some activity against a disease by fast virtual screening of the large molecular libraries, (ii) refinement of selected lead compounds in order to increase their biological activity, and (iii) identification of domains of proteins and nucleotide sequences representing potential targets for therapy. Special attention is paid in this review to the application of the EIIP/ISM bioinformatics platform along with other experimental techniques (screening of a phage displayed peptide libraries, testing selected peptides and small molecules for antiviral activity in vitro) in development of HIV entry inhibitors, representing a new generation of the AIDS drugs.
Assuntos
Biologia Computacional/métodos , Desenho de Fármacos , Fármacos Anti-HIV , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Modelos Moleculares , Relação Estrutura-AtividadeRESUMO
The ultrasonic extraction (UE) of oil from the seeds of a semi-oriental tobacco (Nicotiana tabacum L.) plant strain by using n-hexane and petroleum ether was studied at different temperatures and seeds-to-solvent ratios. The oil yield depended on the seed comminution, the extraction temperature, the seeds-to-solvent ratio and the type of solvent. The oil yield was much higher if the seeds were ground before extraction. The oil yield increased with increasing the extraction temperature and with decreasing the seeds-to-solvent ratio. n-Hexane was somewhat more efficient in the oil extraction than petroleum ether. In recovering the tobacco seed oil (TSO), the UE was less efficient than the Soxhlet extraction. The advantage of the UE was a relatively high oil yield at 25 degrees C in a shorter time. The kinetics of UE of TSO was described using the model of unsteady diffusion through plant material.
Assuntos
Nicotiana/química , Óleos de Plantas/isolamento & purificação , Ultrassom , Sementes/química , Solventes/químicaRESUMO
The sunflower oil methanolysis was studied in a stirred reactor at different agitation speeds. The measurements of drop size, drop size distribution and the conversion degree demonstrate the effects of the agitation speed in both non-reaction (methanol/sunflower oil) and reaction (methanol/KOH/sunflower oil) systems. Drop size distributions were found to become narrower and shift to smaller sizes with increasing agitation speed as well as with the progress of the methanolysis reaction at a constant agitation speed. During the methanolysis reaction, the Sauter-mean drop diameter stays constant in the initial slow reaction region, rapidly decreases during the fast reaction period and finally reaches the equilibrium level. Due to the fact that the interfacial area increases, one can conclude that the rate of reaction occurring at the interface will also be enhanced progressively. The "autocatalytic" behavior of the methanolysis reaction is explained by this "self-enhancement" of the interfacial area, due to intensive drop breakage process.
Assuntos
Metanol/química , Óleos de Plantas/química , Emulsões/química , Hidróxidos/química , Compostos de Potássio/química , Óleo de GirassolRESUMO
The kinetics of ultrasonic extraction of extractive substances (ES) from dry herbs of garden (Salvia officinalis L.) and glutinous (Salvia glutinosa L.) sage using petroleum ether, 70% ethanol or water at 40 degrees C, as well as the composition of dry extracts, were studied. The mechanism of ultrasonic extraction is confirmed to occur in two steps: first, dissolution of the ES near the particle surface (washing) and, second, diffusion from the solid particles to the bulk of the liquid extract (slow extraction). The process is described mathematically using three concepts of the unsteady diffusion through plant material, the film theory and the empirical equation of Ponomaryov. The yield of ES increases with increasing solvent polarity, and nearly the maximum concentration of ES in liquid extracts is achieved for about 20 min. The composition of extracts depends on both the extraction conditions applied and the plant material.
Assuntos
Salvia/química , Ultrassom , Cinética , Componentes Aéreos da Planta/química , Extratos Vegetais/química , SolventesRESUMO
Addition of an amendment or reagent to soil/sediment is a technique that can decrease mobility and reduce bioavailability of uranium (U) and other heavy metals in the contaminated site. According to data from literature and results obtained in field studies, the general mineral class of apatites was selected as a most promising amendment for in situ immobilization/remediation of U. In this work we presented theoretical assessment of stability of U(VI) in four apatite systems (hydroxyapatite (HAP), North Carolina Apatite (NCA), Lisina Apatite (LA), and Apatite II) in order to determine an optimal apatite soil amendment which could be used for in situ remediation of uranium. In this analysis we used a theoretical criterion which is based on calculation of the ion-ion interaction potential, representing the main term of the cohesive energy of the matrix/pollutant system. The presented results of this analysis indicate (i) that the mechanism of immobilization of U by natural apatites depends on their chemical composition and (ii) that all analyzed apatites represent, from the point of view of stability, promising materials which could be used in field remediation of U-contaminated sites.
Assuntos
Apatitas , Modelos Teóricos , Fosfatos , Compostos de Urânio , Gerenciamento de Resíduos/métodos , Adsorção , Metais Pesados , Poluentes Radioativos do Solo , Contaminação Radioativa da Água/prevenção & controleRESUMO
Recently, it has been recognised that the amino acid motif VQL(N/V)ES is shared between the second conserved domain of human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (gp120) and the first framework (FW1) of human IgG heavy chain variable region (subgroup III) (VHIII). We have found that nucleotide sequence corresponding to this motif contains some recombination elements characteristic for the genes of human Ig heavy-chain variable region. The possible role of the Ig recombination elements in HIV-1 envelope gene variability, AIDS pathogenesis and vaccine design is discussed.
Assuntos
Proteína gp120 do Envelope de HIV/genética , HIV-1/genética , Região Variável de Imunoglobulina/genética , Recombinação Genética , Sequência de Aminoácidos , Sequência de Bases , Sequência Consenso , Humanos , Dados de Sequência Molecular , Homologia de Sequência do Ácido NucleicoRESUMO
The production of neutralizing antibodies against the central portion of HIV-1 gp120 requires cooperation between T cell and B cell epitopes of this region. We found a motif common to the carboxyterminus of the second conserved region of HIV-1 gp120 and sequences of some human proteins, most of which participate in immune response. The sequence of gp120 of HTLV-IIIB with the highest T-cell reactivity incorporates this motif. It is suggested that the existence of this sequence motif in the central region of the HIV-1 gp120 molecule prevents the production of neutralizing antibodies against the virus in humans.
Assuntos
Anticorpos Antivirais/biossíntese , Proteína gp120 do Envelope de HIV/imunologia , HIV-1/imunologia , Proteínas/imunologia , Sequência de Aminoácidos , Anticorpos Antivirais/imunologia , Antígenos CD/imunologia , Substâncias de Crescimento/imunologia , Proteína gp120 do Envelope de HIV/genética , HIV-1/genética , Humanos , Tolerância Imunológica , Dados de Sequência Molecular , Testes de Neutralização , Homologia de Sequência do Ácido Nucleico , Linfócitos T/imunologiaRESUMO
Twenty-five V3 loops of envelope gp 120 extracted from 30 HIV-1 isolates were compared with T-cell receptor (TCR) subunits variable (V) portions using pairwise alignments of 11-residue peptides. The results indicate that, in comparison with random sequences, the analyzed V3 loops, unlike control (unrelated) sequences, display highly significant local similarity with TCR V delta (p approximately 10(-20)). However, pattern-matching searches were performed on a much larger number of V3 loops (484). In particular, selective pattern TR * * * NT * K * I is shared by V delta from human T-cell line KT19E and 230 HIV-1 V3 loops (N-terminal portion). Pattern RA * YT * * * I * G is common for V delta chain isolated from T-cell line DS6 of an immunodeficient patient and 69 V3 loops (C-terminal portion). The presented delta-chain portions of sequence similarity with the V3 loops overlap the putative complementarity-determining region (CDR3), thus possibly indicating functional similarity too.
Assuntos
Proteína gp120 do Envelope de HIV/química , Proteína gp120 do Envelope de HIV/imunologia , HIV-1/imunologia , Região Variável de Imunoglobulina/química , Receptores de Antígenos de Linfócitos T gama-delta/química , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Homologia de Sequência de Aminoácidos , Sequência de Aminoácidos , Humanos , Complexo Principal de Histocompatibilidade/imunologia , Dados de Sequência MolecularRESUMO
By examining sequence similarity between the V3-loop of gp120 from various HIV-1 isolates and human proteins, we found that the V3 loop portion KKGIAIGPGR in strain New York 5 (HIV-1NY5) shares 70% identical residues with the collagen-like region (CLR) of human complement component C1q-A. C1q CLR was found to react with autoantibodies from several autoimmune disorders. Thus, we assumed that it would be of interest to find out the C1q reactivity with antibodies from AIDS sera. The results obtained show that the V3 loop-derived synthetic peptide KKGIAIGPGRTLY reacts both with AIDS patients sera and with antibodies purified on the V3 loop peptide-affinity column. The same affinity-purified antibodies bind also to C1q molecules. Since, according to our previous results, HIV-1 V3 loops and immunoglobulin heavy chain variable regions (Ig VH) share several common features, we suggest that the envelope of HIV-1NY5 bears a functional internal image of the C1q-A CLR epitope. Therefore, gp120 could manipulate the immune network and contribute to HIV-induced autoimmunity.
Assuntos
Anticorpos Anti-Idiotípicos/genética , Complemento C1q/genética , Proteína gp120 do Envelope de HIV/genética , HIV-1/imunologia , Fragmentos de Peptídeos/genética , Sequência de Aminoácidos , Anticorpos Anti-Idiotípicos/análise , Complemento C1q/imunologia , Proteína gp120 do Envelope de HIV/análise , Proteína gp120 do Envelope de HIV/imunologia , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Região Variável de Imunoglobulina/genética , Dados de Sequência Molecular , Fragmentos de Peptídeos/análise , Homologia de Sequência de AminoácidosRESUMO
A structural relation between consensus sequences of the portion of HIV-1 gp120 involving the V3 loop (V3 peptide) and the variable domains of human immunoglobulin members of the VH-III gene family was proposed to trigger an imbalance of the idiotypic network during the course of HIV infection. Thus, the repertoires of immunoglobulins in healthy individuals should contain antigenic determinant(s) complementary to particular V3 loop epitope(s). In this study we investigated the specific binding to the V3 peptide of antibodies present in sera of HIV-positive and of clinically normal HIV-negative subjects. Two groups of HIV-positive sera differing in antibody titers to V3 peptide, arbitrarily referred here as high- and low-reactive HIV-positive sera, were distinguished on the basis of an ELISA. Antibodies were affinity purified on V3 peptide and their titers in both HIV-negative and low-reactive HIV-positive sera were nearly superimposable and much lower than the titers of those from high-reactive HIV-positive sera. Also, the quality of the two groups of antibodies differed: much higher amounts of soluble V3 peptide were needed to partly compete the binding of antibodies from HIV-negative sera to insoluble V3 peptide as compared with those from HIV-positive sera, suggesting that the latter had higher affinity for V3 peptide. All of the affinity-purified antibodies bound poorly to unrelated peptides, even to those sharing sequence similarity with the V3 peptide. The present observations suggest that in HIV infection antigen-driven affinity maturation of preimmune immunoglobulins with idiotypes complementary to V3 epitope(s) participating in physiological autoreactivity might be at work.
Assuntos
Anticorpos Anti-HIV/sangue , Anticorpos Anti-HIV/imunologia , Proteína gp120 do Envelope de HIV/imunologia , Soronegatividade para HIV/imunologia , Fragmentos de Peptídeos/imunologia , Sequência de Aminoácidos , Afinidade de Anticorpos , Reações Antígeno-Anticorpo , Ensaio de Imunoadsorção Enzimática , Epitopos/imunologia , Anticorpos Anti-HIV/isolamento & purificação , Infecções por HIV/imunologia , Humanos , Idiótipos de Imunoglobulinas/imunologia , Dados de Sequência MolecularRESUMO
An HIV-positive patient presented with pulmonary tuberculosis as her AIDS-defining diagnosis in 1993 and was effectively treated with 12 months of standard antituberculosis medications (isoniazide, rifampin, and pyrazinamide for 2 months). She received zidovudine for 6 weeks at the time of her diagnosis; however, because of patient preference, she has not received subsequent standard HIV medications (7 years). Her CD4 count at the time of diagnosis (1993) was 297/microL. Monthly passive immunotherapy was administered (fresh frozen plasma from HIV-negative blood donors with a significant titer for the anti-vasoactive intestinal peptide [VIP]/NTM antibody) from December 1993 to June 1994. Her CD4 count increased to > 400/microL during the passive immunotherapy and has remained stable for the past 6 years. The rational for the use of anti-VIP/NTM antibodies preparations in HIV, the possible mode of action of anti-VIP/NTM antibodies, the use of Ig preparations, and the role of exercise as a natural source of anti-VIP/NTM antibodies are discussed. This case report supports the potential therapeutic use of anti-VIP antibodies for treatment of HIV disease.
Assuntos
Anticorpos/administração & dosagem , Infecções por HIV/terapia , Imunização Passiva , Peptídeo Intestinal Vasoativo/imunologia , Terapia por Exercício , Feminino , Infecções por HIV/imunologia , Humanos , Imunoglobulinas/uso terapêutico , Pessoa de Meia-Idade , Tuberculose Pulmonar/complicaçõesRESUMO
Heparin given over a long term by a subcutaneous route consistently lowers blood pressure in the hypertensive rat models. The decrease in blood pressure is accompanied by a parallel decrease in hematocrit suggesting a causal relationship between hematocrit and blood pressure. The aim of this study was to define the relationships between acute and chronic hematocrit changes and blood pressure in the normotensive and hypertensive states. Normotensive Wistar (NWR) and spontaneously hypertensive (SHR) rats were used. Hematocrit was decreased acutely by blood-letting, and chronically by treatment with either heparin (H) or phenylhydrazine (P) for 4 weeks. Acute and chronic hematocrit increase was accomplished by packed cells transfusion. Systolic blood pressure was measured weekly; and at the end of the experimental period, plasma volume, cardiac output, and mean arterial pressure were obtained. Acute hematocrit decrease or increase (hematocrit ranging from 25 to 65%) did not affect blood pressure in either strain of rats; whereas chronic hematocrit changes (hematocrit ranging from 35 to 61%) significantly affected blood pressure only in SHR. Thus, chronic hematocrit decrease induced by H or P resulted in a significant fall in blood pressure compared to control (201 +/- 3 v 175 +/- 4, 167 +/- 4 mm Hg, respectively; P < .05). Conversely, a chronic hematocrit increase resulted in a significant rise in blood pressure (201 +/- 3 v 219 +/- 4 mm Hg; P < .05). Similar hematocrit changes produced in NWR, as in SHR, did not affect blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Sistema Cardiovascular/fisiopatologia , Hematócrito , Hemodinâmica , Hipertensão/fisiopatologia , Animais , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Wistar , Valores de Referência , Fatores de TempoRESUMO
To examine whether changes in renomedullary osmolality and the activity of the renin-angiotensin system may influence the ability of the renal medulla to exert an antihypertensive function, rats were exposed to several manoeuvers. These affected either the medullary osmolality or the renin-angiotensin system (salt or saccharose load, salt depletion, treatment with captopril alone or in combination with salt depletion). A comparison of the antihypertensive capacity of the renal medulla was studied by transplanting renal medullae from the various groups into one-kidney one-clip hypertensive rats. A significant and quantitatively similar reduction in blood pressure was observed in hypertensive rats that received transplants of the medullae from control, salt or saccharose loaded rats and captopril treated rats. In contrast, medullae from salt depleted rats did not affect blood pressure when transplanted into hypertensive animals. The addition of captopril restored the antihypertensive function of renal medulla in salt depleted rats. The results do not support the view that osmolality of the renal medulla regulates its antihypertensive capacity, and suggest that angiotensin II may restrain renomedullary antihypertensive function.
Assuntos
Pressão Sanguínea/fisiologia , Hipertensão Renovascular/fisiopatologia , Medula Renal/fisiologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Captopril/farmacologia , Feminino , Medula Renal/transplante , Masculino , Ratos , Ratos Endogâmicos , Sistema Renina-AngiotensinaRESUMO
It is shown how one can understand the frequencies of occurrence of nucleotides in coding DNA sequences on the basis of electron-ion interaction potential.
Assuntos
Composição de Bases , DNA/análise , Citosina , Eletroquímica , Elétrons , ÍonsRESUMO
Although overexpression of TGF-beta1 protein has been demonstrated in advanced breast cancer (BC) patients, as well as in other solid tumours, the molecular mechanism of this process remains obscure. This paper proposes that a genetic/epigenetic alteration might occur in the TGF-beta1 gene, within the region coding for the recognition site with TGFbeta receptor type II, leading to a disruption of the ligand-receptor interaction and triggering the TGF-beta1 cascade-related BC progression. To establish the operational framework for this hypothesis, in the present study, this recognition site was identified by the Informational Spectrum Method (ISM) to comprise two TGF-beta1 peptides (positions 47-66 aa and 83-112 aa) and one receptor peptide at positions 112-151 aa of the extracellular domain of the receptor (TbetaRIIM). The TbetaRIIM locus was further evaluated by ISM-derived deletion analysis of the TbetaRII sequences. To provide experimental support for the proposed model, a pilot study of plasma TGF-beta1 analysis was performed in advanced BC patients (n = 8). Two commercial ELISA assays, one with specific alphaTGF-beta1 MAb (MAb) and other with TbetaRIIM as the immobilized phase, revealed pronounced differences in the pattern of plasma TGF-beta1 elevation. In MAb-profile, the TGF-beta1 increase was detected in 7 of 8 patients, whereas analogous TbetaRIIM-profile revealed the elevation in 3 of 8 patients, taking a 50% of maximal elevation as the cut-off value. These findings are consistent with the proposed aberration of TGF-beta1 ligand within the TbetaRII recognition site. Summarizing, this model system is a good starting point for further genetic studies, particularly on genetic/epigenetic alterations of sequences involved in TGF-beta1 and TbetaRIIM interaction, with putative prognostic value for breast cancer.
Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/genética , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Análise de Sequência de Proteína/métodos , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Sequência de Aminoácidos , Substituição de Aminoácidos , Sítios de Ligação/genética , Neoplasias da Mama/epidemiologia , Feminino , Perfilação da Expressão Gênica/métodos , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Humanos , Dados de Sequência Molecular , Ligação Proteica , Proteínas Serina-Treonina Quinases , Receptor do Fator de Crescimento Transformador beta Tipo II , Iugoslávia/epidemiologiaRESUMO
This study was aimed at removal of 4-dodecylbenzene sulfonate (DBS) ions from aqueous solutions by ultrasound-assisted adsorption onto the carbonized corn cob (AC). The main attention was focused on modeling the equilibrium and kinetics of adsorption of DBS onto the AC. The AC was prepared from ground dried corn cob by carbonization and activation by carbon dioxide at 880°C for 2h in a rotary furnace. The adsorption isotherm data were fitted by the Langmuir model in both the absence and the presence of ultrasound (US). The maximum adsorption capacities of the adsorbent for DBS, calculated from the Langmuir isotherms, were 29.41mg/g and 27.78mg/g in the presence of US and its absence, respectively. The adsorption process in the absence and the presence of US obeyed the pseudo second-order kinetics. The intraparticular diffusion model indicated that the adsorption of DBS ions on the AC was diffusion controlled as well as that US promoted intraparticular diffusion. The ΔG° values, -24.03kJ/mol, -25.78kJ/mol and -27.78kJ/mol, were negative at all operating temperatures, verifying that the adsorption of DBS ions was spontaneous and thermodynamically favorable. The positive value of ΔS°=187J/molK indicated the increased randomness at the adsorbent-adsorbate interface during the adsorption of DBS ions by the AC.