RESUMO
Hydra is a small freshwater polyp capable of regeneration from small tissue pieces and from aggregates of cells. During regeneration, a hollow bilayered sphere is formed that undergoes osmotically driven shape oscillations of inflation and rupture. These oscillations are necessary for successful regeneration. Eventually, the oscillating sphere breaks rotational symmetry along the future head-foot axis of the animal. Notably, the shape oscillations show an abrupt shift from large-amplitude, long-period oscillations to small-amplitude, short-period oscillations. It has been widely accepted that this shift in oscillation pattern is linked to symmetry breaking and axis formation, and current theoretical models of Hydra symmetry breaking use this assumption as a model constraint. However, a mechanistic explanation for the shift in oscillation pattern is lacking. Using in vivo manipulation and imaging, we quantified the shape oscillation dynamics and dissected the timing and triggers of the pattern shift. Our experiments demonstrate that the shift in the shape oscillation pattern in regenerating Hydra tissue pieces is caused by the formation of a functional mouth and not by shape symmetry breaking as previously assumed. Thus, model assumptions must be revised in light of these new experimental data, which can be used to constrain and validate improved theoretical models of pattern formation in Hydra.
Assuntos
Fenômenos Biofísicos , Hydra/fisiologia , Boca/fisiologia , Regeneração/fisiologia , Animais , Modelos BiológicosRESUMO
PURPOSE: Measurement of the second virial coefficient B22 for proteins using self-interaction chromatography (SIC) is becoming an increasingly important technique for studying their solution behaviour. In common with all physicochemical chromatographic methods, measuring the dead volume of the SIC packed column is crucial for accurate retention data; this paper examines best practise for dead volume determination. METHOD: SIC type experiments using catalase, BSA, lysozyme and a mAb as model systems are reported, as well as a number of dead column measurements. RESULTS: It was observed that lysozyme and mAb interacted specifically with Toyopearl AF-Formyl dead columns depending upon pH and [NaCl], invalidating their dead volume usage. Toyopearl AF-Amino packed dead columns showed no such problems and acted as suitable dead columns without any solution condition dependency. Dead volume determinations using dextran MW standards with protein immobilised SIC columns provided dead volume estimates close to those obtained using Toyopearl AF-Amino dead columns. CONCLUSION: It is concluded that specific interactions between proteins, including mAbs, and select SIC support phases can compromise the use of some standard approaches for estimating the dead volume of SIC columns. Two other methods were shown to provide good estimates for the dead volume.
Assuntos
Anticorpos Monoclonais/química , Cromatografia/métodos , Animais , Bovinos , Galinhas , Muramidase/química , Soroalbumina Bovina/química , Soluções/químicaRESUMO
OBJECTIVES: Osteogenesis imperfecta (OI) frequently leads to long-bone bowing requiring a surgical intervention in severe cases to avoid subsequent fractures. However, there are no objective criteria to decide when to perform such intervention. The objective is to develop a finite element model to predict the risk of tibial fracture associated with tibia deformity in patients with OI. METHODS: A comprehensive FE model of the tibia was adapted to match bi-planar radiographs of a 7 year-old girl with OI. Ten additional models with different deformed geometries (from 2° to 24°) were created and the elasto-plastic mechanical properties were adapted to reflect OI conditions. Loads were obtained from mechanography of two-legged hopping. Two additional impact cases (lateral and torsion) were also simulated. Principal strain levels were used to define a risk criterion. RESULTS: Fracture risks for the two-legged hopping load case remained low and constant until tibia bowing reached 15° and 16° in sagittal and coronal planes respectively. Fracture risks for lateral and torsion impact were equivalent whatever the level of tibial bowing. CONCLUSIONS: The finite element model of OI tibia provides an objective means of assessing the necessity of surgical intervention for a given level of tibia bowing in OI-affected children.
Assuntos
Análise de Elementos Finitos , Osteogênese Imperfeita/complicações , Fraturas da Tíbia/etiologia , Fraturas da Tíbia/prevenção & controle , Fenômenos Biomecânicos , Criança , Feminino , Humanos , Fatores de Risco , Tíbia/anormalidades , Tíbia/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
A TG microsatellite in the 3'-untranslated region (UTR) of FGF9 mRNA has previously been shown to modulate FGF9 expression. In the present study, we investigate the possible interacting protein that binds to FGF9 3'-UTR UG-repeat and study the mechanism underlying this protein-RNA interaction. We first applied RNA pull-down assays and LC-MS analysis to identify proteins associated with this repetitive sequence. Among the identified proteins, FUBP3 specifically bound to the synthetic (UG)(15) oligoribonucleotide as shown by supershift in RNA-EMSA experiments. The endogenous FGF9 protein was upregulated in response to transient overexpression and downregulated after knockdown of FUBP3 in HEK293 cells. As the relative levels of FGF9 mRNA were similar in these two conditions, and the depletion of FUBP3 had no effect on the turn-over rate of FGF9 mRNA, these data suggested that FUBP3 regulates FGF9 expression at the post-transcriptional level. Further examination using ribosome complex pull-down assay showed overexpression of FUBP3 promotes FGF9 expression. In contrast, polyribosome-associated FGF9 mRNA decreased significantly in FUBP3-knockdown HEK293 cells. Finally, reporter assay suggested a synergistic effect of the (UG)-motif with FUBP3 to fine-tune the expression of FGF9. Altogether, results from this study showed the novel RNA-binding property of FUBP3 and the interaction between FUBP3 and FGF9 3'-UTR UG-repeat promoting FGF9 mRNA translation.
Assuntos
Proteínas de Ligação a DNA/metabolismo , Fator 9 de Crescimento de Fibroblastos/genética , Regulação da Expressão Gênica , Repetições de Microssatélites , Biossíntese de Proteínas , Proteínas de Ligação a RNA/metabolismo , Fatores de Transcrição/metabolismo , Regiões 3' não Traduzidas , Sequência de Bases , Linhagem Celular , Fator 9 de Crescimento de Fibroblastos/biossíntese , Células HEK293 , Humanos , Dados de Sequência Molecular , Oligorribonucleotídeos/metabolismoRESUMO
The aim of this study was to investigate the effect of processing route (i.e., quench cooling and ball milling) on the surface energy heterogeneity and surface chemistry of indomethacin (IMC). Recently developed inverse gas chromatography (IGC) methodology at finite concentrations was employed to determine the surface energy distributions of crystalline, quench cooled and milled IMC samples. Surface properties of crystalline and processed IMC were measurably different as determined by the IGC and other conventional characterization techniques: differential scanning calorimetry and powder X-ray diffraction. Quench cooled IMC was in fully amorphous form. Milled IMC showed no amorphous character by calorimetric or X-ray diffraction studies. It was demonstrated that both processed IMC samples were energetically more active than the crystalline IMC. In particular, milled IMC exhibited a relatively higher dispersive surface energy and higher surface basicity (electron donor capability). This may be attributed to the creation of surface defect sites or exposure of higher energy crystal facets during the milling process. This study confirms that processing route has notable influence on the surface energy distribution and surface acid-base character. IGC was demonstrated as a powerful technique for investigating surface properties of real-world, heterogeneous pharmaceutical materials.
Assuntos
Indometacina/química , Tecnologia Farmacêutica/métodos , Varredura Diferencial de Calorimetria/métodos , Química Farmacêutica/métodos , Cromatografia Gasosa/métodos , Cristalização/métodos , Propriedades de Superfície , Difração de Raios X/métodosRESUMO
A full-length MyD88 cDNA (CiMyD88) was cloned and characterized from grass carp Ctenopharyngodon idella. CiMyD88 was found to be broadly expressed and was up-regulated by grass carp reovirus (GCRV) and CiMyD88 transcripts in vitro were rapidly elevated in C. idella kidney (CIK) cells after challenge with poly(I:C). These results suggest that CiMyD88 may be involved in the antiviral immune defence in C. idella.
Assuntos
Carpas/genética , Carpas/imunologia , Doenças dos Peixes/imunologia , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/imunologia , Infecções por Reoviridae/veterinária , Adjuvantes Imunológicos/farmacologia , Animais , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/imunologia , Dados de Sequência Molecular , Poli I-C/farmacologia , Reoviridae/imunologia , Infecções por Reoviridae/imunologia , Baço/efeitos dos fármacos , Baço/imunologiaRESUMO
We have fabricated and tested the performance of sub-50nm gate nMOSFETs to assess their suitability for mixed signal applications in the super high frequency (SHF) band, i.e. 3-30GHz. For a 30nm×40 µm×2 device, we found f(T) =465GHz at V(ds)=2V, V(g)=0.67V, which is the highest cut-off frequency reported for a MOSFET produced on bulk silicon substrate so far. However, our measurements of f(max) and noise figure indicate that parasitics impose limitations on SHF operation. We also present a high-frequency ac model appropriate to sub-50nm gate length nanotransistors, which incorporates the effects of the parasitics. The model accurately accounts for measurements of the S and Y parameters in the frequency range from 1 to 50GHz.
RESUMO
The generation of glutamatergic neurons by stem and progenitor cells is a complex process involving the tight coordination of multiple cellular activities, including cell cycle exit, initiation of neuronal differentiation and cell migration. The mechanisms that integrate these different events into a coherent program are not well understood. Here we show that the cyclin-dependent kinase inhibitor p27Kip1 plays an important role in neurogenesis in the mouse cerebral cortex, by promoting the differentiation and radial migration of cortical projection neurons. Importantly, p27Kip1 promotes neuronal differentiation and neuronal migration via two distinct mechanisms, which are themselves independent of the cell cycle regulatory function of p27Kip1. p27Kip1 inactivation by gene targeting or RNA interference results in neuronal differentiation and radial migration defects, demonstrating that p27Kip1 regulates cell migration in vivo. The differentiation defect, but not the migration defect, is rescued by overexpression of the proneural gene Neurogenin 2. p27Kip1 acts by stabilizing Neurogenin 2 protein, an activity carried by the N-terminal half of the protein. The migration defect resulting from p27Kp1 inactivation is rescued by blocking RhoA signalling, an activity that resides in the c-terminal half of p27Kip1. Thus, p27Kip1 plays a key role in cortical development, acting as a modular protein that independently regulates and couples multiple cellular pathways contributing to neurogenesis.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/fisiologia , Diferenciação Celular/fisiologia , Movimento Celular/fisiologia , Córtex Cerebral/citologia , Inibidor de Quinase Dependente de Ciclina p27/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Neurônios/citologia , Experimentação Animal , Animais , Ciclo Celular , Córtex Cerebral/crescimento & desenvolvimento , Marcação de Genes , Camundongos , Interferência de RNARESUMO
To address the poor prognosis of mixed lineage leukemia (MLL)-rearranged infant acute lymphoblastic leukemia (iALL), we generated a panel of cell lines from primary patient samples and investigated cytotoxic responses to contemporary and novel Food and Drug Administration-approved chemotherapeutics. To characterize representation of primary disease within cell lines, molecular features were compared using RNA-sequencing and cytogenetics. High-throughput screening revealed variable efficacy of currently used drugs, however identified consistent efficacy of three novel drug classes: proteasome inhibitors, histone deacetylase inhibitors and cyclin-dependent kinase inhibitors. Gene expression of drug targets was highly reproducible comparing iALL cell lines to matched primary specimens. Histone deacetylase inhibitors, including romidepsin (ROM), enhanced the activity of a key component of iALL therapy, cytarabine (ARAC) in vitro and combined administration of ROM and ARAC to xenografted mice further reduced leukemia burden. Molecular studies showed that ROM reduces expression of cytidine deaminase, an enzyme involved in ARAC deactivation, and enhances the DNA damage-response to ARAC. In conclusion, we present a valuable resource for drug discovery, including the first systematic analysis of transcriptome reproducibility in vitro, and have identified ROM as a promising therapeutic for MLL-rearranged iALL.
Assuntos
Depsipeptídeos/farmacologia , Proteína de Leucina Linfoide-Mieloide/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Animais , Antibióticos Antineoplásicos/farmacologia , Linhagem Celular Tumoral/efeitos dos fármacos , Quinases Ciclina-Dependentes/antagonistas & inibidores , Rearranjo Gênico , Xenoenxertos , Inibidores de Histona Desacetilases/farmacologia , Humanos , Recém-Nascido , Camundongos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Inibidores de Proteassoma/farmacologiaRESUMO
Self-interaction chromatography is known to be a fast, automated and promising experimental technique for determination of B22, but with the primary disadvantage of needing a significant amount of protein (>50 mg). This requirement compromises its usage as a technique for the early screening of new biotherapeutic candidates. A new scaled down SIC method has been evaluated here using a number of micro LC columns of different diameters and lengths, using typically 10 times less stationary phase than traditional SIC. Scale-down was successfully accomplished using these micro-columns, where the SIC results for a range of differing columns sizes were in agreement, as reflected by k', B22 and column volumes data. The results reported here demonstrate that a scaled down version of SIC can be easily implemented using conventional liquid chromatography system where the final amount of mAbs used was 10 times less than required by conventional SIC methodologies.
Assuntos
Anticorpos Monoclonais/química , Cromatografia Líquida/métodos , Muramidase/química , Animais , Galinhas , Cromatografia Líquida/instrumentaçãoRESUMO
To improve treatment of acute lymphoblastic leukaemia (ALL), a better understanding of disease development is needed to tailor new therapies. Connective tissue growth factor (CTGF/CCN2) is highly expressed in leukaemia cells from the majority of paediatric patients with B-lineage ALL (pre-B ALL). CTGF is a matricellular protein and plays a role in aggressive cancers. Here we have genetically engineered leukaemia cells to modulate CTGF expression levels. Elevated CTGF levels accelerated disease dissemination and reduced survival in NOD/SCID mice. In vitro studies showed that CTGF protein induces stromal cell proliferation, promotes adhesion of leukaemia cells to stromal cells and leads to overexpression of genes associated with cell cycle and synthesis of extracellular matrix (ECM). Corresponding data from our leukaemia xenograft models demonstrated that CTGF leads to increased proliferation of non-leukaemia cells and deposition of ECM in the bone marrow. We document for the first time a functional role of CTGF in altering disease progression in a lymphoid malignancy. The findings provide support for targeting the bone marrow microenvironment in aggressive forms of leukaemia.
Assuntos
Ciclo Celular/genética , Proliferação de Células/genética , Fator de Crescimento do Tecido Conjuntivo/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Animais , Diferenciação Celular/genética , Fator de Crescimento do Tecido Conjuntivo/antagonistas & inibidores , Progressão da Doença , Matriz Extracelular/genética , Regulação Leucêmica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Células Estromais/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Expected and unexpected bleeding occur frequently in patients undergoing cardiac surgery. Bleeding after cardiac surgery can be broadly divided into two groups: surgical (unrecognized bleeding vessel, anastomosis, or other suture line) or nonsurgical bleeding (caused by coagulopathy). Factors influencing both surgical and nonsurgical bleeding can be further broken down into those occurring preoperatively and those that occur intraoperatively and postoperatively. A thorough understanding of these factors is necessary to reduce bleeding. This is a desirable clinical goal, because excessive bleeding is associated with adverse outcomes.
Assuntos
Antifibrinolíticos/uso terapêutico , Medicina Baseada em Evidências , Transfusão de Plaquetas , Sistemas Automatizados de Assistência Junto ao Leito , Hemorragia Pós-Operatória , Algoritmos , Cardiopatias/cirurgia , Humanos , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/prevenção & controle , Hemorragia Pós-Operatória/terapia , Fatores de RiscoRESUMO
OBJECTIVE: To determine the prevalence of complementary and alternative medicine (CAM) use in Singapore, the factors influencing CAM use, and the attitudes, beliefs and perceptions of the general population towards CAM. DESIGN: An interviewer-administered questionnaire survey in a housing estate with demographic and socioeconomic characteristics closely matching that of Singapore. RESULTS: 76% (95% C.I. 73.9-77.9%) used CAM over a 12-month period. Females were 2.1 times (95% C.I. 1.3-3.4) more likely than males to use CAM. Chinese (84%) were the most frequent users, followed by Malays (69%) and Indians (69%), with adjusted odds ratios of 0.4 (95% C.I. 0.2-0.7) for Malays and 0.4 (95% C.I. 0.2-0.8) for Indians. Traditional Chinese Medicine (88%) was the most widely used form of CAM, followed by Traditional Malay (Jamu) Medicine (8%) and Traditional Indian (Ayuverdic) Medicine (3%). Similar to western studies, CAM was more likely to be used for maintenance of health than for treatment of illness. Different from western studies, CAM use was not independently associated with household income, marital status, age and education. Seventy-four percent did not discuss their use of CAM with their western-trained doctors. CONCLUSIONS: The high prevalence of CAM use in multi-racial Singapore suggests the same may be true in other Asian countries. Western-trained doctors need to understand CAM better and communicate more with their patients regarding CAM use. The lack of a scientific evidence base for most forms of CAM notwithstanding, its ubiquitous use worldwide is something that governments and the medical profession cannot afford to ignore.
Assuntos
Terapias Complementares/estatística & dados numéricos , Medicina Tradicional Chinesa/estatística & dados numéricos , Adulto , Atitude Frente a Saúde , Etnicidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Distribuição por Sexo , Singapura/epidemiologia , Classe Social , Inquéritos e QuestionáriosRESUMO
Basal keratinocyte herniations (BKH) have been used as markers of psoriatic activity. Abnormal multipolypoid forms herniating through large gaps in the basal lamina have been found to characterize biopsies from psoriatic patients with concomitant alpha 1-antitrypsin deficiency, and appear to be a marker of excessive proteolytic activity. The finding of similar multipolypoid BKH in patients with generalized pustular psoriasis of the von Zumbusch variety (but not in patients with psoriasis vulgaris), in the absence of concomitant alpha 1-antitrypsin deficiency, would support the concept of the presence of large amounts of proteolytic enzymes in the dermis of patients with this syndrome. The large proportion of BKH directly associated with dermal neutrophils, and the presence of clusters of high-density BKH overlying collections of dermal neutrophils, suggests that neutrophilic proteases are largely responsible for BKH formation in patients with this syndrome.
Assuntos
Psoríase/patologia , Pele/patologia , Adulto , Epiderme/patologia , Feminino , Humanos , Queratinas , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Neutrófilos/patologia , Neutrófilos/ultraestrutura , Fenótipo , Pele/ultraestrutura , alfa 1-Antitripsina/metabolismoRESUMO
Immunity to viral infections involves both innate and antigen-specific immune responses. The antiviral properties of interferons (IFNs) are part of the innate immune response. Low doses of type I IFNs (IFN-alpha and IFN-beta) administered daily (10 IU per mouse) by the oral route significantly reduced the early replication of murine cytomegalovirus (MCMV) in both the spleen and liver of MCMV-infected susceptible BALB/c mice. Significant inhibition of virus replication was observed for two different inoculum doses of virus (2 x 10(4) pfu per mouse [0.6 LD50] and 2 x 10(4.12) pfu per mouse [0.8 LD50]). Analysis of IFN retention, using [35S]-labeled IFN-alpha1 compared with the nonreceptor binding mutant IFN-alpha1 (R33M) administered orally to mice, revealed binding of wild-type IFN-alpha1 to several tissues. In particular, IFN was retained by tissues proximal to lymphoid regions, including the posterior nasal cavity, posterior tongue, small intestine, and rectum. These findings suggest that type I IFNs may inhibit MCMV replication by distal binding of the orally administered IFN to various tissues, which in turn augment the primary immune response to virus infection.
Assuntos
Muromegalovirus/fisiologia , Replicação Viral , Administração Oral , Animais , Relação Dose-Resposta a Droga , Fígado/virologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Baço/virologia , Fatores de TempoRESUMO
PURPOSE: Ethambutol is an essential medication in the management of tuberculosis. However, it can cause an optic neuropathy of uncertain etiology. Ethambutol toxicity was therefore studied in rodent retinal cells, and agents that might block its toxicity were considered. METHODS: The toxicity of ethambutol and related agents was evaluated in rodent retinal dissociated cell preparations and whole eyes. Calcium fluxes and mitochondrial function were evaluated by fluorescent and staining techniques. For in vivo assays, adult rats were administered oral ethambutol over a 3-month period. Cell survival was assessed by stereology. RESULTS: Ethambutol is specifically toxic to retinal ganglion cells in vitro and in vivo. Endogenous glutamate is necessary for the full expression of ethambutol toxicity, and glutamate antagonists prevent ethambutol-mediated cell loss. Ethambutol causes a decrease in cytosolic calcium, an increase in mitochondrial calcium, and an increase in the mitochondrial membrane potential. CONCLUSIONS: The visual loss associated with ethambutol may be mediated through an excitotoxic pathway, inasmuch as ganglion cells are rendered sensitive to normally tolerated levels of extracellular glutamate. Ethambutol perturbs mitochondrial function. Its toxicity may depend on decreased ATPase activity and mitochondrial energy homeostasis. Glutamate antagonists may be useful in limiting the side effects seen with ethambutol.
Assuntos
Antituberculosos/toxicidade , Etambutol/toxicidade , Ácido Glutâmico/metabolismo , N-Metilaspartato/antagonistas & inibidores , Células Ganglionares da Retina/efeitos dos fármacos , Animais , Cálcio/metabolismo , Carbocianinas/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Etilenodiaminas/toxicidade , Antagonistas de Aminoácidos Excitatórios/farmacologia , Corantes Fluorescentes , Memantina/farmacologia , Potenciais da Membrana/efeitos dos fármacos , Mitocôndrias/fisiologia , Ratos , Células Ganglionares da Retina/metabolismo , Células Ganglionares da Retina/patologia , Sais de Tetrazólio/metabolismo , Tiazóis/metabolismoRESUMO
Glutamate toxicity in retinal ganglion cells has been well documented both in vitro and in vitro, and may play a role in both normal neuronal development and a variety of pathological states. Glutamate receptors are found on cell bodies and neuronal processes, both axons and dendrites. Other work has suggested that one or more of these locales may play a more pronounced role in glutamate-mediated toxicity. We now report that N-methyl-D-aspartate (NMDA) is more toxic to retinal ganglion cells with neurites. Cells without neurites were relatively unaffected by glutamate or NMDA. Cells with longer neurites or more neurite branch points were more likely to sustain NMDA-mediated neurotoxicity. These observations suggest that glutamate-mediated loss may be mediated through NMDA receptors found on neurites, rather than through a direct effect on the cell body.
Assuntos
Axônios/fisiologia , Proteínas do Citoesqueleto/análise , Dendritos/fisiologia , Neuritos/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia , Células Ganglionares da Retina/fisiologia , Animais , Células Cultivadas , Maleato de Dizocilpina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Proteínas Associadas aos Microtúbulos/análise , Neuritos/química , Neuritos/ultraestrutura , Ratos , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/ultraestrutura , Proteínas tau/análiseRESUMO
The development of neuronal polarity and morphology is essential for a functioning nervous system. The present study was undertaken to explore whether blockade of specific channels alter neuronal morphology. Retinal ganglion cells were cultured in the presence of antagonists to NMDA, AMPA/kainate, L-, N-, P-, and Q-type voltage-dependent calcium channels (VDCCs). Five parameters were measured under these conditions: the number of neurites at the cell body, total neurite length, the length of the longest neurite, the number of branch points per neurite, and the diameter of the cell soma. Antagonists to NMDA and L-type VDCCs reduce the number of neurites at the cell body; antagonists to P- and Q-type VDCCs increase the number of neurites. Antagonists to the N-type VDCCs increase total neurite outgrowth, while antagonists to the NMDA and P-type channels reduce total neurite length. Antagonists to the NMDA and L-type channels increase the length of a single neurite, while decreasing the number of branch points; antagonists to the P- and Q-type VDCCs do essentially the opposite-increase the number of neurites, while decreasing the length of each. Blockade of one or more cation channels in developing retinal ganglion cells significantly perturbs neurite morphology. This study may help elucidate part of the role that cation channel signaling plays in neuritic development.
Assuntos
Canais de Cálcio Tipo N , Canais de Cálcio/fisiologia , Neuritos/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia , Células Ganglionares da Retina/química , Células Ganglionares da Retina/citologia , ômega-Conotoxinas , 2-Amino-5-fosfonovalerato/farmacologia , 6-Ciano-7-nitroquinoxalina-2,3-diona/farmacologia , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/análise , Canais de Cálcio Tipo L , Polaridade Celular/efeitos dos fármacos , Tamanho Celular/efeitos dos fármacos , Maleato de Dizocilpina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Potenciais da Membrana/efeitos dos fármacos , Neuritos/química , Nimodipina/farmacologia , Peptídeos/farmacologia , Ratos , Receptores de N-Metil-D-Aspartato/análise , Células Ganglionares da Retina/ultraestrutura , Venenos de Aranha/farmacologia , Antígenos Thy-1/análise , ômega-Agatoxina IVA , ômega-Conotoxina GVIARESUMO
A 48 year old female with complex cyanotic heart disease and pulmonary hypertension was partly cyanosed because of a persistent left superior vena cava draining into an unroofed coronary sinus. The left superior vena cava, which measured 22 mm in diameter, was successfully occluded with a Günther Tulip Vena Cava Mreye Filter which acted as a barrier for embolisation coils.