RESUMO
Being in vicinity of vast deserts, the west and southwest of Iran are characterized by high levels of dust events, which have adverse consequences on human health, ecosystems, and environment. Using ground based dataset of dust events in western Iran and NCEP/NCAR reanalysis data, the atmospheric circulation patterns of dust events in the Arabian region and west of Iran are identified. The atmospheric circulation patterns which lead to dust events in the Arabian region and western Iran were classified into two main categories: the Shamal dust events that occurs in warm period of year and the frontal dust events as cold period pattern. In frontal dust events, the western trough or blocking pattern at mid-level leads to frontogenesis, instability, and air uplift at lower levels of troposphere in the southwest of Asia. Non-frontal is other pattern of dust event in the cold period and dust generation are due to the regional circulation systems at the lower level of troposphere. In Shamal wind pattern, the Saudi Arabian anticyclone, Turkmenistan anticyclone, and Zagros thermal low play the key roles in formation of this pattern. Summer and transitional patterns are two sub-categories of summer Shamal wind pattern. In summer trough pattern, the mid-tropospheric trough leads to intensify the surface thermal systems in the Middle East and causes instability and rising of wind speed in the region. In synthetic pattern of Shamal wind and summer trough, dust is created by the impact of a trough in mid-levels of troposphere as well as existing the mentioned regional systems which are contributed in formation of summer Shamal wind pattern.
Assuntos
Poluentes Atmosféricos/análise , Tempestades Ciclônicas , Clima Desértico , Poeira/análise , Monitoramento Ambiental/métodos , Ecossistema , Humanos , Irã (Geográfico) , Meteorologia , Estações do Ano , VentoRESUMO
Carrier erythrocytes is one of the most promising systemic drug delivery systems investigated in recent decades. In this study, human erythrocytes have been loaded with interferon-alpha 2b (IFN) with the aim to benefit the reticuloendothelial system (RES) targeting potential of the carrier cells. Hypotonic preswelling method was used for drug loading in erythrocytes and the entire loading procedure was evaluated and validated. The loaded amount, entrapment efficiency and cell recovery of the loading procedure were 2906.33+/-588.35IU/0.1ml, 14.53+/-2.94%, and 83.61+/-0.49%, respectively, all being practically feasible. The carrier erythrocytes were characterized in vitro in terms of their drug release kinetics, hematological indices, particle size distribution, SEM analysis, and osmotic and turbulence fragility. IFN release from carrier cells was a relatively rapid process in comparison to the cell lysis kinetics, which is unusual considering the whole body of data published on this delivery system and other protein drugs, so far. All the tested in vitro characteristics showed significant, sometimes notable changes upon drug loading procedure, both with and without the drug.
Assuntos
Portadores de Fármacos , Eritrócitos/metabolismo , Interferon-alfa/metabolismo , Sistema Fagocitário Mononuclear/metabolismo , Adulto , Química Farmacêutica , Composição de Medicamentos , Deformação Eritrocítica , Índices de Eritrócitos , Eritrócitos/química , Eritrócitos/ultraestrutura , Estudos de Viabilidade , Hemoglobinas/metabolismo , Hemólise , Humanos , Soluções Hipotônicas , Técnicas In Vitro , Interferon alfa-2 , Interferon-alfa/química , Cinética , Microscopia Eletrônica de Varredura , Fragilidade Osmótica , Pressão Osmótica , Tamanho da Partícula , Proteínas Recombinantes , Reprodutibilidade dos Testes , Solubilidade , Tecnologia Farmacêutica/métodosRESUMO
Erythrocytes as the most readily available and abundant cells within the body, have been studied extensively for their potential application as drug delivery carriers. In this study, human erythrocytes have been loaded by bovine serum albumin (BSA) as a model antigen/protein using hypotonic preswelling method for targeted delivery of this antigen to antigen-presenting cells (APCs). A series of in vitro tests have been carried out to characterize the carrier cells in vitro, including loading parameters, BSA and hemoglobin release kinetics, hematological indices, particle size distribution, SEM analysis, osmotic and turbulence fragility, and osmotic competency. BSA was loaded in erythrocytes with a loaded amount of 1.98+/-0.009mg with antigen release from carrier cells showing a zero-order kinetic consistent to that of the cell lysis. The apparent cell sizes, measured using laser scattering, were not significantly different from normal erythrocytes, but the real sizes, measured using SEM, and surface topologies were quite different between loaded and unloaded cells. The BSA-loaded cells were remarkably more fragile and less deformable compared to the normal cells. Totally, BSA-loaded erythrocytes seem to be a promising delivery system for reticuloendothelial system (RES) targeting of the antigens.
Assuntos
Portadores de Fármacos , Eritrócitos/metabolismo , Vacinas/administração & dosagem , Adulto , Deformação Eritrocítica , Hemoglobinas/administração & dosagem , Humanos , Microscopia Eletrônica de Varredura , Fragilidade Osmótica , Tamanho da Partícula , Soroalbumina Bovina/administração & dosagem , Vacinas/metabolismoRESUMO
Determining the activity of viral and cellular regulatory elements in B or T lymphoid cell lines would facilitate appropriate utilization of the regulatory sequences for gene transfer- and expression-dependent applications. We have compared the activity of the CMV, RSV and SV40 viral promoter/enhancers as well as the Vlambda1 cellular promoter, in three B cell lines (REH, SMS-SB, C3P), three T cell lines (CEM, Jurkat, ST-F10), and two non-lymphoid cell lines (K-562, HeLa) using the luciferase reporter gene. In B cell lines, the activity of the CMV promoter/enhancer construct was the highest ranging from 10- to 113-fold greater than that of SV40. In contrast, in T cell lines the RSV promoter/enhancer activity was 11-65-fold higher than that of SV40. The Vlambda1 promoter activity was close to that of SV40 promoter/enhancer in most of the cell lines tested. We conclude that CMV and RSV promoter/enhancers contain stronger regulatory elements than do the SV40 and Vlambda1 for expression of genes in lymphoid cell lines.
Assuntos
Vírus do Sarcoma Aviário/genética , Linfócitos B/virologia , Citomegalovirus/genética , Regiões Promotoras Genéticas , Vírus 40 dos Símios/genética , Linfócitos T/virologia , Linhagem Celular , Elementos Facilitadores Genéticos , Expressão Gênica , Técnicas de Transferência de Genes , Vetores Genéticos , Humanos , Sequências Reguladoras de Ácido Nucleico/genética , Células Tumorais CultivadasRESUMO
Recombination activating genes RAG1 and RAG2 are essential components of V(D)J recombination, a process that generates the specific antigen receptors in lymphocytes. To understand the mechanisms underlying the lineage and developmental regulation of transcription of RAG2, we have characterized the human RAG2 exon 1A promoter. In this study, a series of deletion constructs were used to isolate the promoter while a linker scanning approach was taken to assess functionally relevant cis elements within the promoter. Two regulatory domains were identified. The -140 to -123 region is critical for promoter activity in all cell lines tested. Mutations to the putative Ets (-122 to -118) or to the C/EBP (-137 to -129) consensus core sequences did abrogate promoter activity, although specific DNA/protein interactions remained, as determined by EMSA. The -69 to -48 region demonstrates lineage specific promoter activity. Mutations to an overlapping, BSAP-myb-Ikaros-myb site (-65 to -39) resulted in differential promoter activity in human B and T cells. EMSA analysis of this region showed a B cell specific protein complex. Transfection of BSAP into cell lines trans-activates the human RAG2 promoter. We conclude that transcriptional regulation of the human RAG2 gene is complex, involving both tissue specific and ubiquitous factors, and both proximal and distal regulatory elements.
Assuntos
Proteínas de Ligação a DNA/genética , Regiões Promotoras Genéticas , Sequência de Bases , Éxons , Células HeLa , Humanos , Células Jurkat , Células K562 , Dados de Sequência Molecular , Mutagênese , Proteínas Nucleares , Células Tumorais CultivadasRESUMO
Although there is evidence that group I metabotropic glutamate receptors participate in long-term potentiation, the role of these receptors remains unclear. Among antagonists of group I metabotropic glutamate receptors, the mGluR5-selective 6-methyl-2-(phenylethynyl)-pyridine inhibited long-term potentiation in the CA1 region of hippocampal slices from 30-day-old rats, whereas (RS)-1-aminoindan-1,5-dicarboxylic acid and cyclopropan[b]chromen-1a-carboxylic acid ethylester, which are more selective for mGluR1, failed to inhibit long-term potentiation. Evidence also indicates that arachidonic acid is required for long-term potentiation, as inhibition of phospholipase A(2) blocks long-term potentiation. Administration of arachidonic acid immediately after tetanic stimulation restored long-term potentiation that had been inhibited by group I antagonists. Furthermore, arachidonic acid overcame inhibition of long-term potentiation by xestospongin C, an inositol triphosphate receptor channel blocker, or by thapsigargin, an agent that depletes intracellular calcium stores. However, arachidonic acid did not restore long-term potentiation blocked by N-methyl-D-aspartate receptor antagonists. Although it has been assumed that the source of the arachidonic acid necessary for long-term potentiation is N-methyl-D-aspartate receptor activation, our results suggest that during long-term potentiation group I metabotropic glutamate receptors cause arachidonic acid release by mobilization of intracellular calcium.
Assuntos
Ácido Araquidônico/farmacologia , Hipocampo/fisiologia , Potenciação de Longa Duração/efeitos dos fármacos , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Animais , Cálcio/metabolismo , Técnicas In Vitro , Membranas Intracelulares/metabolismo , Potenciação de Longa Duração/fisiologia , Masculino , Ratos , Ratos Sprague-Dawley , Receptores de Glutamato Metabotrópico/fisiologiaRESUMO
Recombination activating gene 1 (RAG1) and RAG2 are the essential and tissue-specific components of V(D)J recombination. We have characterized the genomic organization of the human RAG locus, mapped the transcriptional initiation sites, and partially sequenced and performed functional reporter assays on the 5' flanking regions of human RAG1 and RAG2. Transcription initiation sites were mapped by rapid amplification of 5' cDNA ends, primer extension, and/or RNase protection in normal thymocytes, three pre-B cell lines, and a mature B cell line. A single promoter region was used for RAG1 transcription. In contrast, transcription of RAG2 initiates at two distinct regions of the genome. The 5'-flanking region of the human RAG2 gene is TATA-less; however, there is a GATAA consensus at position -34 with respect to the major transcriptional initiation site of RAG1. Promoter regions of human RAG1 and RAG2 are active in both lymphoid and nonlymphoid cell lines, suggesting that an outside regulatory element is probably involved in the tissue-specific transcriptional regulation of the RAG genes.
Assuntos
Proteínas de Ligação a DNA/genética , Genes RAG-1/genética , Genoma Humano , Regiões Promotoras Genéticas/genética , Sequência de Bases , Clonagem Molecular , DNA Complementar/genética , Humanos , Dados de Sequência Molecular , Proteínas NuclearesRESUMO
We examined the response of tattoo pigments treated with three commercially available lasers: Q-switched ruby, Q-Switched neodynium:yttrium,aluminum,garnet (Nd:YAG), and the alexandrite. Tattoos applied to hairless guinea pigs and treated with the aforementioned lasers were evaluated clinically, histologically, and ultrastructurally. Clinical evaluation showed red brown, dark brown, and orange pigment responded best to the Nd:YAG laser (1064 nm). The alexandrite laser was most effective for removing blue and green pigment, the Q-switched ruby laser was most effective for removing purple and violet pigment, and the Nd:YAG laser (532 nm) removed red pigment the best. Black pigment was lightened equally with the Nd:YAG laser (1064 nm) and (532 nm) and the alexandrite laser (755 nm). No clinical scarring was observed; however, some colors turned black after treatment. Histologic and ultrastructural examination showed epidermal and dermal damage to be most evident after treatment with the Nd:YAG laser. Our study shows that certain tattoo pigments respond better to different laser systems.
Assuntos
Terapia a Laser , Pele/patologia , Tatuagem , Óxido de Alumínio , Silicatos de Alumínio , Animais , Berílio , Grânulos Citoplasmáticos/ultraestrutura , Epiderme/patologia , Epiderme/efeitos da radiação , Epiderme/ultraestrutura , Fibroblastos/ultraestrutura , Cobaias , Macrófagos/ultraestrutura , Microscopia Eletrônica , Neodímio , Organelas/ultraestrutura , Pigmentos Biológicos/efeitos da radiação , Pele/efeitos da radiação , Pele/ultraestrutura , ÍtrioRESUMO
A single shab gene exists in the lobster, Panulirus interruptus, and undergoes alternate splicing to produce multiple transcripts. Using in situ hybridization we have determined the expression pattern of the shab gene in identified neurons of the pyloric network. The shab gene is consistently expressed at a low level in the Ventricular Dilator cell, a high level in the Pyloric Dilator cell, and is not detectably expressed in the Lateral Pyloric or Inferior Cardiac cells. Shab gene expression in the Anterior Burster cell varies from animal to animal. The electrophysiologically heterogeneous group of eight Pyloric Constrictor cells also shows differences in shab gene expression. These results support the idea that differences in shab gene expression contribute to the unique electrophysiological phenotypes displayed by each cell type.