RESUMO
Muonic helium atom hyperfine structure (HFS) measurements are a sensitive tool to test the three-body atomic system and bound-state quantum electrodynamics theory, and determine fundamental constants of the negative muon magnetic moment and mass. The world's most intense pulsed negative muon beam at the Muon Science Facility of the Japan Proton Accelerator Research Complex allows improvement of previous measurements and testing further CPT invariance by comparing the magnetic moments and masses of positive and negative muons (second-generation leptons). We report new ground-state HFS measurements of muonic helium-4 atoms at a near-zero magnetic field, performed for the first time using a small admixture of CH_{4} as an electron donor to form neutral muonic helium atoms efficiently. Our analysis gives Δν=4464.980(20) MHz (4.5 ppm), which is more precise than both previous measurements at weak and high fields. The muonium ground-state HFS was also measured under the same conditions to investigate the isotopic effect on the frequency shift due to the gas density dependence in He with CH_{4} admixture and compared with previous studies. Muonium and muonic helium can be regarded as light and heavy hydrogen isotopes with an isotopic mass ratio of 36. No isotopic effect was observed within the current experimental precision.
RESUMO
BACKGROUND: Facial psoriasis was reported in 17-68% of patients with psoriasis and shown to have a negative impact on patients' personal and health-related quality of life (HRQoL). OBJECTIVES: To explore the association of facial psoriasis with patients' HRQoL and to assess the relationship between ixekizumab (IXE) and improvement in facial psoriasis and changes in HRQoL. METHODS: This work reports the combined results of two phase III multicentre, randomized, double-blind, placebo-controlled, active-comparator trials in patients with moderate-to-severe psoriasis. Patients received placebo, etanercept (ETN; 50 mg twice weekly) or IXE [80 mg every 4 weeks (Q4W) or every 2 weeks (Q2W)] for up to 12 weeks following an initial 160-mg dose. HRQoL parameters were analysed based on facial psoriasis status at baseline using analysis of covariance models. Improvement was assessed as percentage of patients with no facial psoriasis. RESULTS: The combined database included 1133 patients with facial psoriasis and 1437 without. Patients treated with IXE whose facial psoriasis cleared had improved Dermatology Life Quality Index 0.1 responses (P < 0.01) compared with patients with facial psoriasis at Week 12. At Week 12, clearance of facial psoriasis compared with the presence of facial psoriasis was independently associated with significantly better improvement in Psoriasis Skin Appearance Bothersomeness scores in the IXE Q2W treatment group (P < 0.01). At Week 12, facial clearance and overall Psoriasis Area Severity Index (PASI) improvement were observed in significant numbers of patients treated with IXE compared with ETN and placebo. Facial psoriasis clearance at Week 12 in patients treated with IXE or ETN was positively associated with PASI75 and PASI90 achievement. CONCLUSION: Facial psoriasis had a larger negative impact on HRQoL than no facial psoriasis. Facial psoriasis clearance was associated with improved HRQoL. Significantly more IXE-treated patients had rapid facial clearance vs. ETN and PBO, which led to better clinical outcomes.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Dermatoses Faciais/tratamento farmacológico , Psoríase/tratamento farmacológico , Qualidade de Vida , Adulto , Método Duplo-Cego , Etanercepte/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
The gullet worms, classical Gongylonema pulchrum and newly differentiated Gongylonema nepalensis, are prevalent in various mammals in Japan and Sardinia, Italy, respectively. The former species is cosmopolitan in distribution, dwelling in the mucosa of the upper digestive tract of a variety of domestic and wild mammals, and also humans. At present, the geographical distribution of G. nepalensis is known in Nepal and Sardinia, with the nematode having been recorded from the oesophagus of water buffaloes (Nepal), cattle, sheep, goats and wild mouflon (Sardinia). To clarify their natural transmission cycles among domestic and wild mammals, the present study analysed the ribosomal RNA gene (rDNA) and mitochondrial cytochrome c oxidase subunit 1 gene (cox1) of worms of various origins: G. pulchrum worms from sika deer, wild boars, Japanese macaques, and feral alien Reeves's muntjacs in Japan, and G. nepalensis worms from a red fox and a wild boar in Sardinia. Although the internal transcribed spacer (ITS) regions of rDNA and partial cox1 nucleotide sequences of G. pulchrum from native wild mammals in Japan were distinct from those of the worms in cattle, the worms from feral alien Reeves's muntjacs showed the cattle-type ITS genotype and cox1 cattle-I and II haplotypes. The rDNA and cox1 nucleotide sequences of G. nepalensis from a red fox in Sardinia were almost identical to those of the worms from domestic and wild ruminants on the island. The ecological interaction between domestic and wild mammals and their susceptibility to different Gongylonema spp. must be considered when trying to elucidate this spirurid's transmission dynamics in nature.
Assuntos
Animais Selvagens/parasitologia , Infecções por Spirurida/veterinária , Spiruroidea/isolamento & purificação , Animais , Búfalos/parasitologia , Bovinos , Doenças dos Bovinos/parasitologia , Cervos/parasitologia , Complexo IV da Cadeia de Transporte de Elétrons/genética , Doenças das Cabras/parasitologia , Cabras , Haplótipos , Proteínas de Helminto/genética , Itália , Japão , Nepal , Ovinos , Doenças dos Ovinos/parasitologia , Infecções por Spirurida/parasitologia , Spiruroidea/classificação , Spiruroidea/genética , Sus scrofa/parasitologiaRESUMO
The frequency shift of the center-of-mass oscillation, known as the (1,0) mode, of a trapped electron plasma and, furthermore, its time evolution were observed during the cooling of an injected antiproton beam for the first time. Here, antiprotons mixed with the electrons did not follow faster electron oscillations but contributed to the modification of the effective potential. The time evolution of the plasma temperature, deduced from the frequency shift of the excited (3,0) mode, suggested that there was an abnormal energy deposition of the antiproton beam in the electron plasma before thermalization.
RESUMO
The gullet worm (Gongylonema pulchrum) has been recorded from a variety of mammals worldwide, including monkeys and humans. Due to its wide host range, it has been suggested that the worm may be transmitted locally to any mammalian host by chance. To investigate this notion, the ribosomal RNA gene (rDNA), mainly regions of the internal transcribed spacers (ITS) 1 and 2, and a cytochrome c oxidase subunit I (COI) region of mitochondrial DNA of G. pulchrum were characterized using parasites from the following hosts located in Japan: cattle, sika deer, wild boars, Japanese macaques, a feral Reeves's muntjac and captive squirrel monkeys. The rDNA nucleotide sequences of G. pulchrum were generally well conserved regardless of their host origin. However, a few insertions/deletions of nucleotides along with a few base substitutions in the ITS1 and ITS2 regions were observed in G. pulchrum from sika deer, wild boars and Japanese macaques, and those differed from G. pulchrum in cattle, the feral Reeves's muntjac and captive squirrel monkeys. The COI sequences of G. pulchrum were further divided into multiple haplotypes and two groups of haplotypes, i.e. those from a majority of sika deer, wild boars and Japanese macaques and those from cattle and zoo animals, were clearly differentiated. Our findings indicate that domestic and sylvatic transmission cycles of the gullet worm are currently present, at least in Japan.
Assuntos
Variação Genética , Infecções por Spirurida/veterinária , Spiruroidea/classificação , Spiruroidea/genética , Animais , Animais Selvagens , Bovinos , DNA Mitocondrial/química , DNA Mitocondrial/genética , DNA Ribossômico/química , DNA Ribossômico/genética , DNA Espaçador Ribossômico/química , DNA Espaçador Ribossômico/genética , Complexo IV da Cadeia de Transporte de Elétrons/genética , Feminino , Haplótipos , Japão , Masculino , Dados de Sequência Molecular , Mutagênese Insercional , RNA Ribossômico/genética , Análise de Sequência de DNA , Deleção de Sequência , Infecções por Spirurida/parasitologia , Spiruroidea/isolamento & purificaçãoRESUMO
Dendritic cells (DCs) are potent antigen-presenting cells that play a critical role in the initiation of antitumor immune responses. In this study, we show that genetic modifications of a murine epidermis-derived DC line and primary bone marrow-derived DCs to express a model antigen beta-galactosidase (betagal) can be achieved through the use of a replication-deficient, recombinant adenovirus vector, and that the modified DCs are capable of eliciting antigen-specific, MHC-restricted CTL responses. Importantly, using a murine metastatic lung tumor model with syngeneic colon carcinoma cells expressing betagal, we show that immunization of mice with the genetically modified DC line or bone marrow DCs confers potent protection against a lethal tumor challenge, as well as suppression of preestablished tumors, resulting in a significant survival advantage. We conclude that genetic modification of DCs to express antigens that are also expressed in tumors can lead to antigen-specific, antitumor killer cells, with a concomitant resistance to tumor challenge and a decrease in the size of existing tumors.
Assuntos
Adenocarcinoma/imunologia , Adenoviridae/genética , Neoplasias do Colo/imunologia , DNA Complementar/imunologia , Células Dendríticas/imunologia , Células Dendríticas/transplante , Imunoterapia Adotiva/métodos , beta-Galactosidase/imunologia , Adenocarcinoma/prevenção & controle , Adenocarcinoma/terapia , Adenoviridae/imunologia , Animais , Células da Medula Óssea/imunologia , Células da Medula Óssea/virologia , Transplante de Medula Óssea , Linhagem Celular , Neoplasias do Colo/prevenção & controle , Neoplasias do Colo/terapia , Células Dendríticas/virologia , Técnicas de Transferência de Genes , Vetores Genéticos/imunologia , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/secundário , Ativação Linfocitária/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Imunológicos , Transplante de Neoplasias , Linfócitos T Citotóxicos/imunologiaRESUMO
Low energy antiprotons have been used previously to give benchmark data for theories of atomic collisions. Here we present measurements of the cross section for single, nondissociative ionization of molecular hydrogen for impact of antiprotons with kinetic energies in the range 2-11 keV, i.e., in the velocity interval of 0.3-0.65 a.u. We find a cross section which is proportional to the projectile velocity, which is quite unlike the behavior of corresponding atomic cross sections, and which has never previously been observed experimentally.
RESUMO
We report here the first successful synthesis of cold antihydrogen atoms employing a cusp trap, which consists of a superconducting anti-Helmholtz coil and a stack of multiple ring electrodes. This success opens a new path to make a stringent test of the CPT symmetry via high precision microwave spectroscopy of ground-state hyperfine transitions of antihydrogen atoms.
RESUMO
Onchocerca eberhardi n. sp. from the sika deer, Cervus nippon, in Japan is described. Adult worms lived in the carpal ligament; infection reached high levels (up to 25 female and 16 male worms in a single carpal limb). Skin dwelling microfilariae were mainly found in the ears. Prevalence of infection was 81% at the type locality, Mt. Sobo, in Kyushu. The new material was compared to the 31 species of Onchocerca presently known. Onchocerca eberhardi n. sp. females were characterized by a long slender anterior end and a thin esophagus < or =1 mm long with no or only a slight glandular region. The vulva was located near the level of the mid-esophagus and the cuticle had transverse external ridges and internal striae (two striae between adjoining ridges). The most similar species were O. stilesi (re-examined), O. lienalis, and to a lesser extent O. gutturosa, all from bovids (cattle). Two main lineages of Onchocerca are recognized in cervids with either primitive or with derived characteristics (as exemplified by the new species). The species in both lineages are not restricted to cervids but are also found in bovids in the Holarctic region, suggesting that the species diversified in the two host groups simultaneously, when these host groups lived in the some geographic area.
Assuntos
Cervos/parasitologia , Onchocerca/anatomia & histologia , Onchocerca/classificação , Oncocercose/veterinária , Filogenia , Animais , Feminino , Japão , Masculino , Onchocerca/fisiologia , Oncocercose/parasitologia , Especificidade da EspécieRESUMO
Calcitonin gene-related peptide (CGRP) inhibits antigen presentation by Langerhans cells (LC) and macrophages, and LC are anatomically associated with CGRP-containing epidermal nerves. To determine whether CGRP may produce some of its functional effects through regulation of cytokine expression, we utilized enzyme-linked immunosorbent assay (ELISA) of conditioned supernatants to examine production of interleukin (IL)-10 and IL-1 beta protein in the LC-like cell line XS52 as well as the reverse transcriptase-polymerase chain reaction (RT-PCR) to examine levels of mRNA for IL-10, IL-1 beta, and the 40-kDa subunit (p40) of IL-12. CGRP augmented the lipopolysaccharide (LPS) and granulocyte-macrophage colony-stimulating factor (GM-CSF) -induced release of IL-10 protein and the induced expression of IL-10 mRNA in these cells. However, it suppressed the induction of release of IL-1 beta protein and the induction of mRNA for IL-12 p40 and IL-1 beta by LPS and GM-CSF. Regulation of cytokine expression in peritoneal macrophages was also examined. By ELISA, the LPS-induced expression of IL-10 was augmented by CGRP, whereas the induction of IL-1 beta was suppressed. Northern analysis demonstrated augmentation of LPS-induced IL-10 mRNA levels and inhibition of LPS-induced IL-1 beta mRNA by CGRP. CGRP inhibited the LPS-induced induction of IL-12 mRNA as assessed by RT-PCR. Up-regulation of B7-2 expression by LPS and GM-CSF was suppressed by CGRP in both XS52 cells and macrophages, as previously reported. This suppression, however, could be abrogated by co-culture with neutralizing antibodies to IL-10. Furthermore, the presence of neutralizing antibodies to IL-10 during exposure of epidermal cells (EC) to CGRP prevented the CGRP-mediated suppression of EC presentation of tumor-associated antigens (from the S1509a spindle cell carcinoma) for elicitation of delayed-type hypersensitivity in S1509a-immune mice. These data suggest that suppression of antigen-presenting function by CGRP is mediated, at least in part, by changes in cytokine expression that favor less robust antigen presentation for cell-mediated immunity.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Citocinas/biossíntese , Células de Langerhans/metabolismo , Macrófagos Peritoneais/metabolismo , Animais , Anticorpos/farmacologia , Antígenos CD/biossíntese , Antígeno B7-2 , Linhagem Celular , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Interleucina-1/biossíntese , Interleucina-10/biossíntese , Interleucina-10/imunologia , Interleucina-12/biossíntese , Células de Langerhans/efeitos dos fármacos , Células de Langerhans/imunologia , Lipopolissacarídeos/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/imunologia , Glicoproteínas de Membrana/biossíntese , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Epidermal Langerhans cells are frequently anatomically associated with calcitonin gene-related peptide-containing nerves. Furthermore, calcitonin gene-related peptide inhibits Langerhans cells antigen-presenting function in several assays. Studies were performed to further explore the hypothesis that Langerhans cells and nerves have a functional relationship. To examine whether Langerhans cells may produce factors that influence nerve cell differentiation, we utilized the Langerhans cell-like cell line XS52 as a surrogate for Langerhans cells and compared it with Langerhans cells enriched to 90%. Supernatants conditioned by lipopolysaccharide-stimulated XS52 cells were able to induce the differentiation of the pheochromocytoma line PC12 into sympathetic neuron-like cells. This was also the case with enriched Langerhans cells stimulated by lipopolysaccharide. Pretreatment of conditioned supernatants with specific neutralizing anti-sera indicated that most of the differentiation-inducing activity was due to interleukin-6 and a small amount was due to nerve growth factor and basic fibroblast growth factor. By reverse transcriptase polymerase chain reaction, three clones of the XS52 cell line, XS52-4D, XS52-11D, and XS52-8B, were found to express mRNA for interleukin-6 and expression was markedly augmented by lipopolysaccharide. mRNA for nerve growth factor and basic fibroblast growth factor was detected in XS52-4D and XS52-11D, but not in XS52-8B. The expression of these neurotrophic factors by enriched Langerhans cells was quite similar to that of XS52-4D. In order to examine whether Langerhans cells may express receptors for nerve-derived peptides, reverse transcriptase polymerase chain reaction was employed to look for pituitary adenylate cyclase activating polypeptide type I, type II, and type III, and gastrin-releasing peptide receptors. All clones examined, as well as enriched Langerhans cells, expressed pituitary adenylate cyclase activating polypeptide type II and type III, and gastrin-releasing peptide receptors. These results suggest bi-directional signalling between Langerhans cells and nerves; nerve cells may regulate Langerhans cell function by elaboration of certain neuropeptides whereas Langerhans cells may promote the differentation of nerves by elaboration of interleukin-6 and, possibly, other factors.
Assuntos
Células de Langerhans/metabolismo , Fatores de Crescimento Neural/metabolismo , Receptores de Neuropeptídeos/metabolismo , Animais , Diferenciação Celular , Linhagem Celular , Epiderme/inervação , Fator 2 de Crescimento de Fibroblastos/genética , Fator 2 de Crescimento de Fibroblastos/imunologia , Soros Imunes/farmacologia , Interleucina-6/genética , Interleucina-6/imunologia , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Fatores de Crescimento Neural/genética , Fatores de Crescimento Neural/imunologia , Fenômenos Fisiológicos do Sistema Nervoso , Inibição Neural , Neuritos/efeitos dos fármacos , Neuritos/fisiologia , Células PC12/patologia , Células PC12/fisiologia , RNA Mensageiro/metabolismo , RatosRESUMO
CGRP is a neuropeptide that has previously been described to possess immunosuppressive activities. CGRP is released from peripheral nerves that, in the skin, are in close physical association with dendritic APC. We sought to investigate the mechanisms by which CGRP can inhibit immune responses by studying its effects on human peripheral blood mononuclear cells (PBMC). Using allogeneic monocytes as stimulator cells, CGRP could inhibit the proliferation of PBMC by 47% when CGRP was present for the duration of culture. Interestingly, when the stimulator monocytes were incubated with CGRP for 2 h prior to irradiation then washed, the observed inhibition increased to 85%, suggesting that CGRP was exerting a direct effect on the monocyte stimulator population. Finally, the recall response to tetanus toxoid (TT) by PBMC from individuals vaccinated with TT 14 d prior was inhibited by 25-50% in the presence of CGRP. Also, CGRP decreased the levels of B7.2 but not B7.1 on treated monocytes, and this inhibition could be abrogated by the addition of anti-IL-10 antibody, suggesting that the inhibition was mediated by an increase in IL-10 production. Moreover, increased IL-10 production was confirmed by ELISA. Both IL-12 p40 and IFN-gamma levels in CGRP-treated cultures were found to be decreased by approximately 30%. The decrease in IL-12 p40 levels could be reversed by addition of anti-IL-10. These data suggest that CGRP inhibits PBMC proliferation, in part, through the release of IL-10, which in turn can downregulate important co-stimulatory molecules and the cytokines IL-12 and IFN-gamma.
Assuntos
Antígenos CD/fisiologia , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/imunologia , Glicoproteínas de Membrana/fisiologia , Apresentação de Antígeno/efeitos dos fármacos , Antígeno B7-2 , Divisão Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Humanos , Interferon gama/biossíntese , Interleucina-10/antagonistas & inibidores , Interleucina-10/metabolismo , Interleucina-10/farmacologia , Interleucina-12/antagonistas & inibidores , Interleucina-12/biossíntese , Interleucina-12/farmacologia , Leucócitos Mononucleares/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
Dendritic antigen-presenting cells derived from epidermis (Langerhans cells), bone marrow, and peripheral blood can present a wide variety of antigens, including tumor-associated antigens, for various immune responses. The development and function of dendritic cells is dependent upon a number of cytokines including granulocyte-macrophage-colony-stimulating factor. For example, Langerhans cells can present tumor-associated antigens for the induction of substantial in vivo anti-tumor immunity but only after activation in vitro by granulocyte-macrophage-colony-stimulating factor. Thus, we reasoned that insertion of a cDNA for granulocyte-macrophage-colony-stimulating factor into dendritic antigen-presenting cells may allow for autocrine stimulation and increased antigen-presenting capability. To test this possibility, we utilized an adenovirus vector to insert a cDNA for murine granulocyte-macrophage-colony-stimulating factor into the dendritic cell lines XS52-4D and XS106 (derived from neonatal mouse epidermis), bone marrow-derived dendritic cells, and epidermal cells that contain Langerhans cells. Infection of each of these cell types resulted in release of abundant quantities of granulocyte-macrophage-colony-stimulating factor. XS52-4D and XS106 cells infected with adenovirus granulocyte-macrophage-colony-stimulating factor exhibited prolonged dendrites and greater expression of major histocompatibility complex class II molecules and CD86 compared with cells infected with a null vector. Granulocyte-macrophage-colony-stimulating factor cDNA-containing XS cells, bone marrow-derived dendritic cells, and epidermal cells had more potent alloantigen presenting capability than cells infected with a null vector. Most importantly, granulocyte-macrophage-colony-stimulating factor gene-transferred epidermal cells were able to present tumor-associated antigens for in vivo anti-tumor immunity against challenge with the S1509a spindle-cell tumor whereas null vector-infected cells were unable to prime for immunity. These results suggest that introduction of a cDNA for granulocyte-macrophage-colony-stimulating factor into dendritic cells may be an effective means to augment their antigen-presenting capability and that granulocyte-macrophage-colony-stimulating factor gene-transfer- red epidermal cells may be useful in tumor vaccination strategies.
Assuntos
Apresentação de Antígeno , Antígenos de Neoplasias/imunologia , Células Dendríticas/fisiologia , Epiderme/imunologia , Técnicas de Transferência de Genes , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Neoplasias Experimentais/imunologia , Animais , Feminino , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BLRESUMO
Neuropeptides/hormones have been shown to regulate the various functions of many immunocompetent cells. A number of neuropeptides/hormones has been demonstrated to be present in the skin and a close anatomical association between calcitonin gene-related peptide (CGRP)-containing nerves and Langerhans cells (LC) has been reported. In addition to the CGRP receptor, receptors for several neuropeptides including pituitary adenylate cyclase activating polypeptide (PACAP) and gastrin releasing peptide (GRP) are found on LC, suggesting these neuropeptides might have some effects on LC. CGRP inhibits alloantigen presentation and stimulation of a specific-antigen responsive T-cell clone by LC. Pre-treatment of LC with CGRP also inhibits the elicitation of delayed type hypersensitivity (DTH) in tumor immune mice. Upregulation of B7-2 expression on LC is suppressed by CGRP, which might be, in part, responsible for the inhibitory effect of CGRP in the functional assay. The production of some inflammatory cytokines such as IL-10 by LC-like cell line XS52 is regulated by CGRP and the functional effect of CGRP appears to be at least partially mediated through the autocrine regulation of IL-10. Alpha-MSH is another neuropeptide, the effect of which has been well studied in the cutaneous immune system. Pre-treatment of mice with alpha-MSH produces inhibitory effects in contact hypersensitivity (CHS). IL-10 has been suggested to be involved in the inhibitory effect of alpha-MSH. The receptors and the functional effects of other proopiomelanocortin (POMC)-derived peptides including beta-endorphin and catecholamines on LC are under investigation.
Assuntos
Hormônios/farmacologia , Células de Langerhans/efeitos dos fármacos , Neuropeptídeos/farmacologia , Animais , Apresentação de Antígeno/fisiologia , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Hormônios/metabolismo , Humanos , Células de Langerhans/imunologia , Camundongos , Neuropeptídeos/metabolismo , Pró-Opiomelanocortina/farmacologia , Receptores de Neuropeptídeos/metabolismo , Receptores de Neuropeptídeos/fisiologia , alfa-MSH/farmacologiaRESUMO
The patient is a 58-year-old Japanese teacher of German literature who suffered twice from cerebrovascular accidents, showing alexia without agraphia. Pathological examination showed an old infarct in the posterior two-thirds of the fusiform and almost the whole lingual gyrus, involving the posterior border of the parahippocampal gyrus in the left hemisphere. The left cuneus and the calcarine cortex were preserved. There was degeneration of the lower third of the splenium of the corpus callosum, extending to its occipital radiation and tapetum on both sides. Comparing clinico-pathological findings of the 31 known autopsy cases, it was proposed that the lesion of the left spleno-lingual system produces alexia without agraphia but it may ameliorate. In addition, when spleno-cuneate system is also involved alexia becomes persistent and it may accompany object agnosia or optic aphasia.
Assuntos
Agrafia/patologia , Dislexia Adquirida/patologia , Agrafia/psicologia , Atrofia , Encéfalo/patologia , Infarto Cerebral/patologia , Transtornos Cerebrovasculares/patologia , Transtornos Cerebrovasculares/psicologia , Dislexia Adquirida/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Destreza Motora , Campos Visuais , Percepção VisualRESUMO
Aqueous vanadate and aqueous tungstate have been known to mimic all or most of the actions of insulin in intact cell systems with respect to normalization of the blood glucose level. By carrying out oral administration in vivo experiments on the blood glucose level of streptozotocin (STZ)-induced diabetes (STZ mice), the insulin-mimetic (IM) effects of metal-oxide clusters of all-inorganic composition were examined using many types of polyoxometalates (POM) with and without vanadium substitution. Several homo-POM and vanadium-substituted POM showed hypoglycemic effects. The observed hypoglycemic effects indicated that POM with the Dawson structure [[alpha-P(2)W(18)O(62)](6-) (W-2), [alpha-P(2)W(17)V(V)O(62)](7-) (V-19) and [alpha-1,2,3-P(2)W(15)V(V)(3)O(62)](9-) (V-04)] are more effective than those with the Keggin structure [[alpha-PW(12)O(40)](3-) (W-1), [alpha-PW(11)V(V)O(40)](4-) (V-01), [alpha-1,2-PW(10)V(V)(2)O(40)](5-) (V-02), [alpha-1,2,3-PW(9)V(V)(3)O(40)](6-) (V-03) and [alpha-1,4,9-PW(9)V(V)(3)O(40)](6-) (V-13)]. The vanadate cluster [V(10)O(28)](6-) (V-15) also showed a hypoglycemic effect. (31)P and (51)V NMR measurements showed that the Dawson POM (W-2, V-04 and V-19) are stable in aqueous solution under the conditions used. The effect of all POM on the body weight of STZ mice was also examined. The decrease in body weight after administration of W-2 was much less than for V-19, V-04 and V-15. This suggests that not only monomeric tungstate and vanadate, but also the structure factors of tungstate and vanadate clusters, can play a significant role in their biological action.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Insulina/farmacologia , Compostos de Tungstênio/farmacologia , Administração Oral , Animais , Estabilidade de Medicamentos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Polímeros/administração & dosagem , Polímeros/química , Polímeros/farmacologia , Soluções , Compostos de Tungstênio/administração & dosagem , Compostos de Tungstênio/químicaRESUMO
There are no previous reports of serial echocardiographic findings in patients with pheochromocytoma. We report a 50-year-old woman with pheochromocytoma who developed acute heart injury. Echocardiography revealed that the acute myocardial injury started early in the base and subsequently extended to the mid-portion of the heart. The injury persisted longer in the base than in the mid-portion.
Assuntos
Neoplasias das Glândulas Suprarrenais/complicações , Miocardite/diagnóstico por imagem , Miocardite/etiologia , Feocromocitoma/complicações , Neoplasias das Glândulas Suprarrenais/sangue , Neoplasias das Glândulas Suprarrenais/fisiopatologia , Ecocardiografia/métodos , Feminino , Hemodinâmica , Humanos , Pessoa de Meia-Idade , Miocardite/sangue , Miocardite/fisiopatologia , Feocromocitoma/sangue , Feocromocitoma/fisiopatologiaRESUMO
In order to clarify the involvement of oxidative stress in in vitro sugar-induced cataractogenesis, we examined changes in lipid peroxide, reduced glutathione, vitamin E, and water contents following cataractogenesis in rat lenses cultured with 20 mM D-xylose over a period of 24 h. In D-xylose-treated lenses, an apparent opacity appeared at the equator after 6 h of D-xylose treatment, increases in lipid peroxide and water contents and decreases in reduced glutathione and vitamin E contents occurred with the appearance of opacity. We further examined the effect of the treatment of vitamin E in a liposomal form on cataractogenesis and the changes of lipid peroxide, reduced glutathione, vitamin E, water, and xylitol contents in rat lenses cultured with 20 mM D-xylose for 24 h. This vitamin E treatment significantly prevented not only cataractogenesis, but also an increase in lipid peroxide content and a decrease in vitamin E content in the D-xylose-treated lenses. However, the vitamin E treatment had no effect not only on a decrease in reduced glutathione content, but also on increases in water and xylitol contents, which are known to be induced via aldose reductase, in the D-xylose-treated lenses. These results indicate that not only osmotic stress but also oxidative stress should be involved in cataractogenesis in rat lenses cultured with D-xylose and support the involvement of oxidative stress in in vitro sugar-induced cataractogenesis.
Assuntos
Catarata/metabolismo , Estresse Oxidativo/fisiologia , Animais , Água Corporal/metabolismo , Catarata/induzido quimicamente , Catarata/prevenção & controle , Meios de Cultura , Técnicas de Cultura , Portadores de Fármacos , Glutationa/metabolismo , Cristalino/efeitos dos fármacos , Peróxidos Lipídicos/metabolismo , Lipossomos , Masculino , Ratos , Ratos Wistar , Fatores de Tempo , Vitamina E/metabolismo , Vitamina E/farmacologia , Xilitol/metabolismo , Xilose/farmacologiaRESUMO
The preventive action of vitamin E (Vit. E)-containing liposomes on cataractogenesis was examined in male Wistar rats (five weeks old) fed a 25% galactose diet. Vit. E-containing liposomes prepared with dipalmitoylphosphatidylcholine were instilled into both eyes three times a day over a 45-day period. Cataract appeared at 18-day galactose feeding and developed gradually thereafter. Simultaneous Vit. E-containing liposome instillation delayed this cataractogenesis. Lenses of 18-day galactose-fed rats showed decreases in Vit. E and reduced glutathione (GSH) contents and Na+, K(+)-ATPase activity and increases in lipid peroxide (LPO), galactitol, and water contents. Lenses of 45-day galactose fed rats showed decreases in GSH content and Na+,K(+)-ATPase activity and increases in Vit. E, LPO, galactitol, and water contents. Serum Vit. E and cholesterol levels decreased in 18-day galactose-fed rats, while both levels increased in 45-day galactose-fed rats. Simultaneous Vit. E-containing liposome instillation prevented these changes except for the changes of lenticular galactitol and water contents and serum Vit. E and cholesterol levels. These results indicate that simultaneously instilled Vit. E-containing liposomes can delay cataractogenesis in young adult rats fed a 25% galactose diet mainly by the antioxidative action of Vit. E contained in the instilled liposomes.