RESUMO
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Bradykinin is the end-product of the kallikrein/kinin system, which has been recognized as an endogenous target for combating CNS inflammation. Angiotensin-converting enzyme (ACE) inhibitors influence the kallikrein/kinin system and reportedly have immunomodulatory characteristics. The objectives of this study were to determine whether bradykinin is involved in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and whether bradykinin control by the ACE inhibitor could be a therapeutic target in MS. The ACE inhibitor enalapril (1·0 or 0·2 mg/kg/day) was administered orally to EAE mice and the serum levels of bradykinin and cytokines in EAE mice were analysed. As a result, the administration of enalapril increased serum bradykinin levels, decreased the clinical and pathological severity of EAE and attenuated interleukin-17-positive cell invasion into the CNS. Additionally, bradykinin receptor antagonist administration reduced the favourable effects of enalapril. Our results suggest that bradykinin is involved in the pathomechanism underlying CNS inflammation in EAE, possibly through inhibiting cell migration into CNS. Control of the kallikrein/kinin system using ACE inhibitors could be a potential therapeutic strategy in MS.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Encefalomielite Autoimune Experimental/metabolismo , Calicreínas/metabolismo , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Animais , Bradicinina/análogos & derivados , Bradicinina/sangue , Bradicinina/metabolismo , Bradicinina/farmacologia , Citocinas/sangue , Citocinas/metabolismo , Doenças Desmielinizantes/tratamento farmacológico , Doenças Desmielinizantes/metabolismo , Modelos Animais de Doenças , Enalapril/administração & dosagem , Enalapril/farmacologia , Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Feminino , Camundongos , Esclerose Múltipla/metabolismo , Índice de Gravidade de Doença , Células Th17/imunologia , Células Th17/patologiaRESUMO
AIMS: Not all the mechanisms by which subthalamic nucleus deep brain stimulation (STN-DBS) alleviates parkinsonian symptoms have been clarified as yet. The levels of striatal monoamine and the subthalamic beta activity might contribute to its efficacy. However, their direct relationship is unclear. We aimed to examine the correlation between the striatal monoamine and the STN beta activity induced by STN-DBS. EXPERIMENTAL PROCEDURES: Experiments were performed under urethane anesthesia in normal (n=4) and 6-hydroxydopamine hemi-lesioned Parkinson's disease (PD) model rats (n=5). STN-DBS was applied to the left STN, and local field potential (LFP) was recorded before and after STN-DBS. Striatal extracellular fluid was collected before, during, and after STN-DBS. Spectral analysis of STN-LFP was performed, and the levels of monoamine were measured. RESULTS: The levels of 3-4-dihydroxyphenylacetic acid (DOPAC) were significantly decreased after the cessation of stimulation in PD model rats. The levels of none of the monoamines were significantly affected in normal rats. The STN beta power was significantly elevated after the cessation of stimulation in normal rats but was significantly decreased in PD model rats. The STN beta power and the levels of DOPAC and 5-HT was positively correlated in PD model rats, whereas the levels of dopamine and 5-HT showed positive correlation and the levels of DOPAC and Homovanillic acid (HVA) showed negative correlation in normal rats. CONCLUSION: STN-DBS could decrease the levels of DOPAC and the STN beta power in a PD model rat. The STN beta power and the levels of striatal monoamine might be differentially correlated between normal and PD model rats.
Assuntos
Monoaminas Biogênicas/metabolismo , Corpo Estriado/metabolismo , Estimulação Elétrica/métodos , Doença de Parkinson/terapia , Núcleo Subtalâmico/fisiologia , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Dopamina/metabolismo , Feminino , Ácido Homovanílico/metabolismo , Atividade Motora/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Oxidopamina/toxicidade , Doença de Parkinson/etiologia , Doença de Parkinson/patologia , Ratos , Ratos Sprague-Dawley , Análise Espectral , Núcleo Subtalâmico/citologiaRESUMO
High mobility group box 1 (HMGB1) is an established inflammatory mediator when released from cells. Recent studies have implicated extracellular HMGB1 in the pathogenesis of various autoimmune diseases. The objective of this study was to determine whether HMGB1 could be a therapeutic target for experimental autoimmune encephalomyelitis (EAE). In this study, an anti-HMGB1 monoclonal antibody was injected intraperitoneally into a mouse model of EAE. We also measured serum cytokines levels in EAE and anti-HMGB1 monoclonal antibody-treated EAE. As a result, intraperitoneal injection of an anti-HMGB1 monoclonal antibody ameliorated the clinical and pathological severity of EAE and attenuated interleukin-17 up-regulation in serum. In conclusion, HMGB1 is involved in EAE pathogenesis and could trigger inflammation in the central nervous system. The novel aspect of this study is the demonstration that anti-HMGB1 ameliorates EAE. HMGB1 may be a novel therapeutic strategy for multiple sclerosis.
Assuntos
Anticorpos Monoclonais/farmacologia , Encefalomielite Autoimune Experimental/tratamento farmacológico , Proteína HMGB1/antagonistas & inibidores , Bainha de Mielina/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Medula Espinal/efeitos dos fármacos , Animais , Anticorpos Monoclonais/imunologia , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/sangue , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Feminino , Expressão Gênica/efeitos dos fármacos , Proteína HMGB1/genética , Proteína HMGB1/imunologia , Inflamação/sangue , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/patologia , Injeções Intraperitoneais , Interleucina-17/sangue , Interleucina-17/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla/sangue , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Bainha de Mielina/imunologia , Bainha de Mielina/patologia , Fármacos Neuroprotetores/imunologia , Índice de Gravidade de Doença , Medula Espinal/imunologia , Medula Espinal/patologiaRESUMO
The repulsive guidance molecule (RGM) is a membrane-bound protein that has diverse functions in the developing central nervous system. Identification of neogenin as a receptor for RGM provided evidence of its cell death-inducing activity in the absence of RGM. Here, we show that the serine/threonine kinase death-associated protein kinase (DAPK) is involved in the signal transduction of neogenin. Neogenin interacts with DAPK and reduces DAPK autophosphorylation on Ser308 in vitro. Neogenin-induced cell death is abolished in the presence of RGM or by blocking DAPK. Although neogenin overexpression or RGM downregulation in the chick neural tube in vivo induces apoptosis, coexpression of the dominant-negative mutant or small-interference RNA of DAPK attenuates this proapoptotic activity. Thus, RGM/neogenin regulates cell fate by controlling the DAPK activity.
Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Apoptose/fisiologia , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Sobrevivência Celular/fisiologia , Proteínas de Membrana/metabolismo , Neurônios/fisiologia , Animais , Linhagem Celular , Embrião de Galinha , Citocromos c/metabolismo , Proteínas Quinases Associadas com Morte Celular , Proteínas Ligadas por GPI , Inativação Gênica , Humanos , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Mitocôndrias/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Tubo Neural/citologia , Tubo Neural/metabolismo , Neurônios/citologia , Ratos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Transdução de Sinais/fisiologia , Técnicas do Sistema de Duplo-HíbridoRESUMO
Myelin-associated glycoprotein (MAG) is a well-characterized axon growth inhibitor in the adult vertebrate nervous system. Several signals that play roles in inhibiting axon growth have been identified. Here, we report that soluble MAG induces activation of Rap1 in postnatal cerebellar granule neurons (CGNs) and dorsal root ganglion (DRG) neurons. The p75 receptor associates with activated Rap1 and is internalized in response to MAG. After MAG is applied to the distal axons of the sciatic nerves, the activated Rap1, internalized p75 receptor, and MAG are retrogradely trafficked via axons to the cell bodies of the DRG neurons. Rap1 activity is required for survival of the DRG neurons as well as CGNs when treated with MAG. The transport of the signaling complex containing the p75 receptor and Rap1 may play a role in the effect of MAG.
Assuntos
Glicoproteína Associada a Mielina/fisiologia , Neurônios/metabolismo , Receptor de Fator de Crescimento Neural/metabolismo , Transdução de Sinais , Proteínas rap1 de Ligação ao GTP/metabolismo , Animais , Axônios/efeitos dos fármacos , Axônios/metabolismo , Células Cultivadas , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Glicoproteína Associada a Mielina/farmacologia , Neurônios/efeitos dos fármacos , Ratos , Proteínas RecombinantesRESUMO
A plasma-electrode Pockels cell (PEPC) has been developed for use on the OMEGA extended performance (EP) laser system that can be used in a high-contrast optical switch, as required for isolation of the system from retroreflected pulses. Contrast ratios reliably exceeded 500:1 locally everywhere in the clear aperture. The key to achieving this improvement was the use of circular windows simply supported on compliant O rings, which is shown to produce very low stress-induced birefringence despite vacuum loading. Reliable operation was achieved operating at a relatively high operating pressure, low operating pressures being found to be strongly correlated to occurrences of local loss of plasma density.
RESUMO
Peripheral quantitative computed tomography (pQCT) is increasingly used for measurement of cortical bone geometry and density in mice. We evaluated the accuracy of pQCT for area and density measurements of thin-walled aluminum phantoms and mouse femora. Aluminum tubes with varying wall thicknesses and femora from 1- to 6-month-old C3H/HeJ (C3H) and C57B1/6J (B6) mice (average cortical thickness 0.14-0.29 mm) were scanned at 70- or 90-microm resolution. pQCT values of area were compared to optical values determined after sectioning, while pQCT density (vBMD) was compared to solid aluminum density or correlated to bone ash content. For the aluminum phantoms, the error in pQCT area and density depended strongly on wall thickness, and density was consistently underestimated. For mouse femora, threshold values were found that produced zero error in bone area for each strain and age group, although the optimal threshold differed between groups. pQCT vBMD correlated strongly with ash content (r2=0.7), although the regression equations differed between strains and the magnitude of the inter-strain difference in vBMD was fourfold greater than the difference in ash content. This finding suggests that pQCT can overestimate the differences in volumetric mineral density between inbred mouse strains whose bones are of different thickness (e.g., C3H vs. B6). In conclusion, both area and density values obtained by pQCT depend strongly on specimen thickness, consistent with a partial volume averaging artifact. Investigators using pQCT to assess cortical bones in mice should be aware of the potential for cortical thickness-dependent errors.
Assuntos
Densidade Óssea , Fêmur/diagnóstico por imagem , Fêmur/metabolismo , Tomografia Computadorizada por Raios X/métodos , Alumínio , Animais , Fêmur/anatomia & histologia , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Imagens de Fantasmas , Reprodutibilidade dos Testes , Especificidade da Espécie , Tomógrafos Computadorizados , Tomografia Computadorizada por Raios X/instrumentaçãoRESUMO
Bose fluids restricted in one dimension (1D) are realized by adsorbing 4He atoms on the 1D pore walls with a diameter of about 18 A. The Bose fluid appears above an adsorbed amount after the pore walls are coated with the inert 4He atoms. Heat capacity of the fluid was observed to have a temperature-linear term at low temperatures. This corresponds to the phonon heat capacity of the Bose fluid in the 1D pores. We estimate the phonon velocity and the interaction of the 1D Bose fluid.
RESUMO
A zinc-resistant bacterium, Brevibacterium sp. strain HZM-1 which shows a high Zn2+ -adsorbing capacity, was isolated from the soil of an abandoned zinc mine. Kinetic analyses showed that Zn2+ binding to HZM-1 cells follows Langmuir isotherm kinetics with a maximum metal capacity of 0.64 mmol/g dry cells and an apparent metal dissociation constant of 0.34 mM. The observed metal-binding capacity was one of the highest values among those reported for known microbial Zn2+ biosorbents. The cells could also adsorb heavy metal ions such as Cu2+. HZM-1 cells could remove relatively low levels of the Zn2+ ion (0.1 mM), even in the presence of large excess amounts (total concentration, 10 mM) of alkali and alkali earth metal ions. Bound Zn2+ ions could be efficiently desorbed by treating the cells with 10 mM HCl or 10 mM EDTA, and the Zn2+ -adsorbing capacity of the cells was fully restored by treatment of the desorbed cells with 0.1 M NaOH. Thus, HZM-1 cells can serve as an excellent biosorbent for removal of Zn2+ from natural environments. The cells could grow in the presence of significant concentrations of ZnCl2 (at least up to 15 mM) and thus is potentially applicable to in situ bioremediation of Zn2+ -contaminated aqueous systems.
Assuntos
Brevibacterium/metabolismo , Zinco/metabolismo , Biodegradação Ambiental , Brevibacterium/classificação , Concentração de Íons de Hidrogênio , Cinética , Filogenia , TemperaturaRESUMO
A rare case of follicular dendritic cell (FDC) sarcoma is reported. A 71-year-old woman was admitted for evaluation of constipation. Computerized tomography showed cervical, supraclavicular, retroperitoneal, and paraaortic lymphadenopathies. Histological findings from a cervical lymph node revealed Hodgkin's disease at first. But tumors that arose both in the cervical and the left interscapular regions during the chemotherapy were immunohistochemically confirmed to be of follicular dendritic cell origin. The ultrastructural findings were consistent with those of FDC sarcoma. FDC sarcoma is a rare nonlymphoid cell-derived malignant tumor originating from the lymphoid tissue. The diagnosis of FDC sarcoma is most accurately established by immunohistochemical methods, using its specific markers.
Assuntos
Células Dendríticas Foliculares/patologia , Células Dendríticas Foliculares/ultraestrutura , Sarcoma/patologia , Sarcoma/ultraestrutura , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/ultraestrutura , Idoso , Feminino , Humanos , Imuno-HistoquímicaRESUMO
Protamine is known to inhibit cation selectivity of the paracellular shunt pathway in several leaky nephron segments. Ion permeability of the superficial (SF) proximal straight tubules (PST) is selective to Cl(-), whereas that of the juxtamedullary (JM) PST is selective to Na(+). Protamine was used to estimate the contribution of the paracellular shunt pathway to ion selectivity in these segments. PSTs were isolated from the kidneys of Japanese white rabbit and microperfused in vitro. The ratio of Na(+) to Cl(-) permeability (P(Na)/P(Cl)) was estimated from the diffusion potential (dV(T)) generated by NaCl gradients. When 300 microg/ml protamine was added to the lumen, P(Na)/P(Cl) was decreased from 0.33 to 0.26 in SF-PST and from 1.80 to 1.29 in JM-PST, respectively, as the results of inhibition of cation selectivity. Addition of 30 U/ml heparin to the lumen, which neutralizes protamine, returned the ratios toward the control levels. Protamine exhibited similar effect on P(Na)/P(Cl) in the presence or the absence of ouabain in the bath, indicating that the observed voltage deflections were independent of the transcellular active transport process. Although P(Na)/P(Cl) was different between SF- and JM-PST, protamine inhibits Na(+) permeability in both segments. Preferential Cl(-) permeability in the SF-PST may be intrinsic to the paracellular route of this segment. The mechanism of this anion selectivity remains to be established.
Assuntos
Antagonistas de Heparina/farmacologia , Medula Renal/metabolismo , Túbulos Renais Proximais/metabolismo , Protaminas/farmacologia , Algoritmos , Animais , Anticoagulantes/farmacologia , Cloretos/metabolismo , Difusão , Eletrofisiologia , Inibidores Enzimáticos/farmacologia , Feminino , Heparina/farmacologia , Medula Renal/irrigação sanguínea , Medula Renal/efeitos dos fármacos , Túbulos Renais Proximais/irrigação sanguínea , Túbulos Renais Proximais/efeitos dos fármacos , Masculino , Microcirculação/efeitos dos fármacos , Ouabaína/farmacologia , CoelhosRESUMO
A patient with primary cardiac lymphoma, which is very rare, generally is regarded to have a poor prognosis. We herein report a patient with cardiac lymphoma who was treated successfully by systemic chemotherapy and radiotherapy using a pacemaker to control the complete atrioventricular (A-V) block. A 70-year-old man had a syncope caused by a complete A-V block. An echocardiogram, a computed tomographic scan, and magnetic resonance imaging of his chest showed a cardiac tumor. At this time, a biopsy of the cardiac tumor disclosed malignant lymphoma (diffuse large cell type, B cell type). The patient was thus treated with systemic chemotherapy and radiotherapy and, as a result, achieved a complete remission with a disappearance of the A-V block. Recently, several successful outcomes involving primary cardiac lymphoma have been reported because of the progress in diagnostic techniques including echocardiography, computed tomographic scanning, and magnetic resonance imaging, as well as improvement in the therapy of malignant lymphoma. Our clinical experience indicated that an early and accurate diagnosis combined with the appropriate therapy can thus help in obtaining a long survival in patients with primary cardiac lymphoma.
Assuntos
Bloqueio Cardíaco/diagnóstico , Bloqueio Cardíaco/terapia , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/terapia , Linfoma/diagnóstico , Linfoma/terapia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/administração & dosagem , Diagnóstico Diferencial , Doxorrubicina/administração & dosagem , Humanos , Masculino , Marca-Passo Artificial , Prednisolona/administração & dosagem , Radioterapia , Vincristina/administração & dosagemRESUMO
The Ca2+-activated maxi K+ channel was found in the apical membrane of everted rabbit connecting tubule (CNT) with a patch-clamp technique. The mean number of open channels (NPo) was markedly increased from 0.007 +/- 0.004 to 0.189 +/- 0.039 (n = 7) by stretching the patch membrane in a cell-attached configuration. This activation was suggested to be coupled with the stretch-activation of Ca2+-permeable cation channels, because the maxi K+ channel was not stretch-activated in both the cell-attached configuration using Ca2+-free pipette and in the inside-out one in the presence of 10 mm EGTA in the cytoplasmic side. The maxi K+ channel was completely blocked by extracellular 1 microM charybdotoxin (CTX), but was not by cytoplasmic 33 microM arachidonic acid (AA). On the other hand, the low-conductance K+ channel, which was also found in the same membrane, was completely inhibited by 11 microM AA, but not by 1 microM CTX. The apical K+ conductance in the CNT was estimated by the deflection of transepithelial voltage (DeltaVt) when luminal K+ concentration was increased from 5 to 15 mEq. When the tubule was perfused with hydraulic pressure of 0.5 KPa, the DeltaVt was only -0. 7 +/- 0.4 mV. However, an increase in luminal fluid flow by increasing perfusion pressure to 1.5 KPa markedly enhanced DeltaVt to -9.4 +/- 0.9 mV. Luminal application of 1 microM CTX reduced the DeltaVt to -1.3 +/- 0.6 mV significantly in 6 tubules, whereas no significant change of DeltaVt was recorded by applying 33 microM AA into the lumen of 5 tubules (DeltaVt = -7.2 +/- 0.5 mV in control vs. DeltaVt = -6.7 +/- 0.6 mV in AA). These results suggest that the Ca2+-activated maxi K+ channel is responsible for flow-dependent K+ secretion by coupling with the stretch-activated Ca2+-permeable cation channel in the rabbit CNT.
Assuntos
Túbulos Renais/metabolismo , Túbulos Renais/fisiologia , Canais de Potássio Cálcio-Ativados , Canais de Potássio/metabolismo , Animais , Ácido Araquidônico/farmacologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Charibdotoxina/farmacologia , Condutividade Elétrica , Canais de Potássio Ativados por Cálcio de Condutância Alta , Masculino , Potenciais da Membrana , Potássio/metabolismo , Bloqueadores dos Canais de Potássio , Canais de Potássio/fisiologia , CoelhosRESUMO
A 20-year-old Japanese female anorectic patient developed primary hypothyroidism associated with generalized edema because of excessive daily intake (40 to 50 g) of confectionery made with tangle weed, Kombu, which she substituted to food during bulimic periods; TSH 60.35 mcU/ml, free T3 1.19 pg/ml, and free T4 0.48 ng/dl, and her weight increased by 12 kg to 45 kg over 4 months. After withdrawal of Kombu her thyroid function returned to normal, and her weight decreased by 7 kg to 38 kg along with disappearance of edema. In conclusion, the physician noticed that susceptible anorectic patients may sometime develop hypothyroidism or hyperthyroidism because of excessive iodine intake of sea-weed confectionery as a substitute of high calorie cakes during bulimic period.
Assuntos
Anorexia Nervosa/complicações , Bulimia/complicações , Doces/efeitos adversos , Hipotireoidismo/induzido quimicamente , Iodo/efeitos adversos , Edulcorantes/efeitos adversos , Adulto , Feminino , Humanos , Iodo/administração & dosagemRESUMO
KMD-3213, (-)-(R)-1-(3-hydroxypropyl)-5-[2-[[2-[2-(2,2,2-trifluoroethoxy)phe noxy]ethyl]amino]propyl]indoline-7-carboxamide, is a novel and selective alpha1A-adrenoceptor antagonist. The potency of this drug to antagonize functional alpha1-adrenoceptor-mediated contraction in human prostatic smooth muscle was evaluated and compared with that of other alpha1-adrenoceptor antagonists. KMD-3213 inhibited noradrenaline-induced contractions with an apparent pK(B) value of 9.45 +/- 0.039, indicating a potency similar to that of tamsulosin. The affinity of prazosin for prostatic alpha1-adrenoceptors is given as potency for the alpha1L-adrenoceptor with an estimated pA2 value of 8.84 +/- 0.044. The data obtained in this study suggest that KMD-3213, an alpha1A-adrenoceptor-selective antagonist, has strong affinity for the alpha1L-adrenoceptor in the human prostate.
Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1 , Antagonistas Adrenérgicos alfa/farmacologia , Indóis/farmacologia , Próstata/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Norepinefrina/antagonistas & inibidores , Prazosina/farmacologia , Próstata/metabolismo , Prostatectomia , Hiperplasia Prostática/fisiopatologia , Hiperplasia Prostática/terapia , Receptores Adrenérgicos alfa 1/fisiologia , Sulfonamidas/farmacologia , TansulosinaRESUMO
OBJECTIVE: To assess the incidence of intranuclear DNA fragmentation and the expression of the bcl-2 oncoprotein in prostatic carcinoma, both of which are related to programmed cell death. PATIENTS, MATERIALS AND METHODS: Specimens of tumour obtained from 17 patients with newly diagnosed prostatic carcinoma and 16 with hormone-treated prostatic carcinoma undergoing total prostatectomy were evaluated. DNA fragmentation was detected using the terminal-labelling method (d-uridine triphosphate conjugated with digoxigenin) and the expression of bcl-2 was detected immunohistochemically. RESULTS: There was a high incidence of intranuclear DNA fragmentation in 14 of 17 untreated tumours and 15 of 16 hormone-treated tumours. There were no differences between the positive cases in hormone-treated tumours and untreated tumours. There was significantly greater expression of bcl-2 in tumours treated with non-steroidal anti-androgen drugs (eight of nine were positive) than in those untreated (seven of 17) or treated with other drugs (one of seven) (P < 0.05). There was a consistent and marked dissociation between DNA fragmentation and bcl-2 positivity; most of the cells positive for bcl-2 showed no DNA fragmentation. CONCLUSION: The results indicated that cells positive for bcl-2 might potentially be hormone resistant and that the administration of non-steroidal anti-androgen drugs might have a role in the induction of hormone-resistant cells.
Assuntos
Apoptose/genética , DNA de Neoplasias , Neoplasias da Próstata/genética , Proteínas Proto-Oncogênicas/metabolismo , Idoso , Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-bcl-2RESUMO
Although the accumulation of urea in the renal medulla is essential for the formation of concentrated urine, it is also necessary for the kidney to excrete considerable amounts of urea into the urine as a waste product of protein degradation. Thus, the urine concentrating capacity is attained by the interaction with the efficiency of urea excretion. To seek the best condition for this phenomenon, we developed an objective function for evaluating urea excreting capacity relative to urine concentrating capacity by using a mathematical model consisting of components of the countercurrent multiplication system: the ascending thin limb, capillary network, and inner medullary collecting duct. The values of the objective functions were calculated as three-dimensional functions of transport parameters for the inner medullary collecting duct, including hydraulic conductivity, urea permeability, and reflection coefficient for urea. The results of the computer analysis revealed that the maximum value of the objective function was attained when values for transport parameters of the inner medullary collecting duct corresponded to those experimentally obtained values reported previously. We conclude that the maximum urine concentrating capacity is limited by the efficiency of urea excreting capacity of the kidney, and vice versa.
Assuntos
Simulação por Computador , Capacidade de Concentração Renal , Medula Renal/metabolismo , Túbulos Renais Coletores/metabolismo , Modelos Biológicos , Ureia/urina , Transporte Biológico , Humanos , Computação MatemáticaRESUMO
Fourteen specimens of human hypertrophied prostate were evaluated for the distribution of alpha 1 adrenoceptors using autoradiography with a computerized image analysis system. The hypertrophied prostatic specimens, obtained at open prostatectomy, were dissected vertically to the urethra, and sectioned at 10 microns. They were immersed in 1 nM of specific alpha 1 ligand, [3H]tamsulosin chloride ([3H]tamsulosin) and exposed to autoradiographic film. The images were analysed by a computerized image analysis system. The total binding of [3H]tamsulosin in the whole section (n = 14) was 0.82 +/- 0.21 (mean +/- SE) nCi mg-1. The autographic data were correlated with data obtained in a membrane-binding assay. The prostatic tissue studied was divided into urethral, glandular and stromal zones, the latter two zones being further divided into the inner and outer areas. The total binding of [3H]tamsulosin in the urethral zone (n = 7) was 0.65 +/- 0.32 nCi mg-1. The glandular zone contained significantly more abundant alpha 1 adrenoceptors than the stromal zone and their densities (glandular vs stromal) were 1.15 +/- 0.19 nCi mg-1 (n = 14) vs 0.72 +/- 0.15 nCi mg-1 (n = 14), respectively (p < 0.05). The data from the whole section were not affected by prostatic weight. This method described enabled the distribution of the receptors in different sites to be evaluated both morphologically and quantitatively.
Assuntos
Antagonistas Adrenérgicos alfa , Hiperplasia Prostática/metabolismo , Receptores Adrenérgicos alfa 1/metabolismo , Sulfonamidas , Antagonistas Adrenérgicos alfa/farmacocinética , Idoso , Autorradiografia , Humanos , Processamento de Imagem Assistida por Computador , Ligantes , Masculino , Membranas/metabolismo , Tamanho do Órgão/fisiologia , Próstata/patologia , Hiperplasia Prostática/patologia , Sulfonamidas/farmacocinética , TansulosinaRESUMO
The physiological significance of the renal interstitium is reviewed with special reference to solute transport. The renal tubules and vasculatures participate in essential parts of the nephron functions. The renal interstitium, interposing among these structures, regulates solute transport across the renal tubules. In the renal cortex, changes in the interstitial pressure modulate the proximal tubular fluid reabsorption via paracellular shunt pathways. In the renal medulla, the interstitium may play an important role in the lateral diffusion of solutes and water, contributing to the mechanisms of urine concentration, as well as, medullary potassium recycling and ammonia excretion.