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1.
Phys Rev Lett ; 114(12): 126401, 2015 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-25860761

RESUMEN

We combine resonant inelastic x-ray scattering and model calculations in the Kondo lattice compound YbInCu_{4}, a system characterized by a dramatic increase in Kondo temperature and associated valence fluctuations below a first-order valence transition at T≃42 K. The bulk-sensitive, element-specific, and valence-projected charge excitation spectra reveal an unusual quasigap in the Yb-derived state density which drives an instability of the electronic structure and renormalizes the low-energy effective Hamiltonian at the transition. Our results provide long-sought experimental evidence for a link between temperature-driven changes in the low-energy Kondo scale and the higher-energy electronic structure of this system.

2.
Phys Rev Lett ; 108(3): 036403, 2012 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-22400765

RESUMEN

We resolved a recent controversy on the structure of the Ce L(3) x-ray absorption spectra (XAS) of CeFe(2); i.e., which of the single impurity Anderson model (SIAM) and the first-principles band calculations based on the density-functional theory (DFT) describes more appropriately the Ce 4f states and their contribution to the Ce L(3) XAS? For this purpose, we examined the core-hole effect in Ce L(3) XAS as an application of our new method taking advantage of resonant x-ray emission spectroscopy. Our result clearly shows that the Ce L(3) XAS structure is caused by the mixed valence 4f character revealed by the core-hole potential effect as indicated by SIAM, but denies the possibility that the L(3) XAS structure is caused by the 5d band structure with a very small core-hole effect as predicted by band calculations based on DFT.

3.
Eur J Gynaecol Oncol ; 31(5): 517-21, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-21061792

RESUMEN

PURPOSE: Established therapeutic guidelines for cervical carcinoma recommend concurrent chemo- and radiotherapy as standard treatment for locally advanced cervical carcinoma. Nedaplatin (CDGP) is a platinum agent developed in Japan that is less nephrotoxic than cisplatin (CDDP), but with equivalent antitumor potency. In the standard dosage regimen for cervical carcinoma, CDGP is administered once every four weeks (monthly regimen). We investigated the efficacy and safety of a new dosage regimen, in which CDGP was administered once weekly for five weeks (weekly regimen). METHODS: We measured plasma platinum concentration of patients after administration of CDGP, and analyzed the relationship between plasma platinum concentration and hematological adverse reactions such as thrombocytopenia and leucopenia. RESULTS: The relative rates of change in platelet and white blood cell counts tended to increase as the plasma concentration of platinum increased. Furthermore, the rate of change in platelet counts in relation to the area under the curve was greater for the monthly regimen as compared to weekly. On the other hand, the relative rates of change in WBC were nearly the same between the regimens. CONCLUSIONS: These findings indicate that when using chemotherapy with CDGP for a patient with a cervical carcinoma, a weekly regimen might reduce the severity of thrombocytopenia, while still exhibiting the same therapeutic efficacy as the monthly regimen.


Asunto(s)
Antineoplásicos/efectos adversos , Leucopenia/inducido químicamente , Compuestos Organoplatinos/efectos adversos , Platino (Metal)/sangre , Trombocitopenia/inducido químicamente , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/radioterapia , Adulto , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Terapia Combinada , Esquema de Medicación , Femenino , Humanos , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/farmacocinética , Proyectos Piloto , Trombocitopenia/prevención & control
4.
In Vivo ; 34(2): 587-594, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32111757

RESUMEN

BACKGROUND/AIM: Epstein-Barr virus (EBV) associates with human chronic periodontitis (CP) progression. We previously demonstrated that butyric acid (BA), produced by periodontopathic bacteria, induced EBV lytic switch activator BZLF1 expression. We investigated whether short chain fatty acids (SCFAs) in CP patients' saliva enabled EBV reactivation. MATERIALS AND METHODS: Saliva was collected from seven CP patients and five periodontally healthy individuals. SCFAs were quantified using HPLC. BZLF1 mRNA and its pertinent protein ZEBRA were determined with Real-time PCR and western blotting. Histone H3 acetylation (AcH3) was further examined. RESULTS: BZLF1 mRNA expression and transcriptional activity in EBV-infected Daudi cells were induced only when treated with the CP saliva. Among SCFAs, BA alone correlated significantly with the BZLF1 transcription (r=0.88; p<0.02). As expected, CP patients' saliva induced AcH3. CONCLUSION: BA in saliva may play a role in EBV reactivation and hence contribute to EBV-related disease progression in CP patients.


Asunto(s)
Ácido Butírico/metabolismo , Periodontitis Crónica/etiología , Periodontitis Crónica/metabolismo , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/virología , Herpesvirus Humano 4/genética , Saliva/metabolismo , Transactivadores/genética , Acetilación , Adulto , Anciano , Periodontitis Crónica/patología , Regulación Viral de la Expresión Génica , Histonas/metabolismo , Interacciones Huésped-Patógeno , Humanos , Persona de Mediana Edad , Proyectos Piloto
5.
In Vivo ; 33(6): 1793-1800, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31662504

RESUMEN

BACKGROUND/AIM: Human chronic periodontitis is a major health problem. Although some oral bacteria have been reported to be putative pathogens, Epstein-Barr virus (EBV) is reported to be associated with the progression of periodontitis. However, the role of EBV in the aetiology of periodontitis is unknown. Therefore, we investigated periodontal pathogenesis of EBV to confirm whether EBV-encoded latent membrane protein 1 (LMP1) induces Interleukin-8 (IL8) production in human gingival cells. MATERIALS AND METHODS: Real-time polymerase chain reaction, luciferase assay, enzyme-linked immunosorbent assay (ELISA), and western blotting were performed for determining IL8 mRNA expression, nuclear factor kappa B (NF-ĸB) transcription, IL8 production, and the phosphorylation of NF-ĸB p65 and Inhibitor of kappa B alpha (IĸBα), respectively, in Ca9-22 human gingival epithelial cells. Two LMP1 mutants lacking C-terminal activating region (CATR) domains responsible for activating NF-ĸB were used. RESULTS: Extremely high IL8 production was induced by LMP1 in time- and dose-dependent manner, where simultaneous phosphorylation of NF-κB p65 and IĸBα and transcription of NF-ĸB were observed. On the contrary, IL8 production and NF-ĸB transcription were drastically inhibited by dominant negative mutant of IĸBα. Moreover, the LMP1 mutants failed to induce IL8 production. CONCLUSION: Our findings suggest that due to CATR domains, LMP1 contributes to the progression of periodontitis via IL8 production attributable to NF-ĸB activation.


Asunto(s)
Periodontitis Crónica/metabolismo , Células Epiteliales/metabolismo , Epitelio/metabolismo , Encía/metabolismo , Herpesvirus Humano 4/metabolismo , Interleucina-8/metabolismo , Proteínas de la Matriz Viral/metabolismo , Línea Celular , Células Epiteliales/virología , Epitelio/virología , Encía/virología , Humanos , FN-kappa B/metabolismo , Transducción de Señal/fisiología , Factor de Transcripción ReIA/metabolismo
6.
Atherosclerosis ; 158(2): 377-84, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11583716

RESUMEN

Vascular smooth muscle cells (SMCs) undergo phenotype change with the development of atherosclerosis. The phenotype changes of SMCs have been observed in various culture conditions, such as collagen-coated dishes. Here, we report the morphological and functional features of SMCs in a novel culture system using type I-collagen in a characteristic three-dimensional structure designated as honeycombs. The number of ribosome and mitochondria in SMCs cultured in honeycombs was one half or third of those cultured on collagen-coated plastic plates. DNA and protein synthesis of SMCs cultured in honeycombs were less than 1 and 30-40%, respectively, of those cultured on plastic plates. In addition, PDGF-BB did not increase the amount of DNA synthesis in SMCs in honeycombs. SMCs in honeycombs were shown to express several proteins, which are known to express in SMCs in medial layers of arteries. Particularly, caldesmon heavy chain was expressed in SMCs cultured in honeycombs, whereas not in those on plastic plates. Although focal adhesion kinase (FAK) was clearly detected in SMCs in honeycomb, the phosphotyrosine content of focal adhesion kin ase decreased in the process of culture. Immunoblot analysis showed dear different expression of ERK1 and ERK2 of mitogen-activated protein kinase in SMCs. SMCs in honeycombs expressed ERK2, more abundantly compared to ERK1, whereas SMCs in plates show the same levels of expressions for both proteins. Thus, the histological and functional feature of SMCs in the novel culture system is different from SMCs in plastic plates. The three-dimensional culture system described here may be indicating that cultured SMCs are able to express different proteins responding to the surrounding structures.


Asunto(s)
Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/ultraestructura , Animales , Aorta Torácica/citología , Proteínas de Unión al Calcio/biosíntesis , Proteínas de Unión a Calmodulina/biosíntesis , División Celular , Células Cultivadas , Colágeno Tipo I , Medios de Cultivo , Proteína-Tirosina Quinasas de Adhesión Focal , Immunoblotting , Masculino , Proteínas de Microfilamentos , Mitocondrias Musculares/ultraestructura , Proteínas Quinasas Activadas por Mitógenos/biosíntesis , Proteínas Musculares/biosíntesis , Miosinas/biosíntesis , Fenotipo , Fosforilación , Factor de Crecimiento Derivado de Plaquetas/farmacología , Proteínas Tirosina Quinasas/metabolismo , Conejos , Ribosomas/ultraestructura , Propiedades de Superficie , Tropomiosina/biosíntesis , Calponinas
7.
Biomaterials ; 18(2): 147-51, 1997 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9022962

RESUMEN

Prehardened calcium phosphate cement consisting of alpha-tricalcium phosphate (alpha-TCP), dicalcium phosphate dibasic (DCPD) and tetracalcium phosphate monoxide (TeCP) was implanted in rabbit mandibles and back muscles, and studied histologically and microradiographically. In the mandibles, new bone formation occurred around the implants and increased in quantity the longer the implant period lasted. Histology, microradiography and scanning electron microscopy (SEM) demonstrated direct contact of bone and cement. Bone response to this cement was essentially the same as to hydroxyapatite (HA) ceramics, known as a biocompatible bone substitute. Material resorption was recognized, which increased with the implant period and was greater in the surface bound by soft tissue than the surface bound by bone tissue. In the back muscles, however, no calcified tissue formation occurred. Resorption proved to be faster than in the case of the mandible implants. It was concluded that the cement, in prehardened form, has good biocompatibility and is a promising material as a bone substitute.


Asunto(s)
Cementos para Huesos , Sustitutos de Huesos , Fosfatos de Calcio , Mandíbula/citología , Animales , Resorción Ósea , Calcificación Fisiológica , Mandíbula/diagnóstico por imagen , Mandíbula/ultraestructura , Microscopía Electrónica de Rastreo , Músculo Esquelético/citología , Músculo Esquelético/diagnóstico por imagen , Osteogénesis , Conejos , Radiografía , Factores de Tiempo
8.
Biomaterials ; 15(6): 429-32, 1994 May.
Artículo en Inglés | MEDLINE | ID: mdl-8080933

RESUMEN

Bone tissue response to pre-hardened alpha-tricalcium phosphate (alpha-TCP) and calcium phosphate dibasic (DCPD) mixture by hydration was studied histologically and microradiographically after implanting on the inferior aspect of the mandible in rabbits. In 1-month implants, new bone formation was observed along the surface of the material near the host bone, and connection of new and host bone through thin bone bridges was seen in some places. In 3-month implants, newly formed bone filled the greater part of the gap between material and host bone, and in 6-month implants, it surrounded almost all the surface of the material. New bone was in direct contact with the material in all implant periods. The bone response was essentially consistent with that to hydroxyapatite (HA). Resorption of the material was noticed in 3- and 6-month implants. It was concluded that pre-hardened alpha-TCP/DCPD mixture has good biocompatibility with bone tissue equal to HA and that it resorbs when implanted in rabbit. Further research should be performed to evaluate the material changes of resorption and formation of the white zone.


Asunto(s)
Materiales Biocompatibles/farmacología , Huesos/efectos de los fármacos , Fosfatos de Calcio/farmacología , Animales , Desarrollo Óseo/efectos de los fármacos , Resorción Ósea , Huesos/anatomía & histología , Huesos/diagnóstico por imagen , Durapatita/farmacología , Mandíbula , Ensayo de Materiales , Conejos , Radiografía
9.
Biomaterials ; 18(7): 539-43, 1997 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-9105593

RESUMEN

alpha-Tricalcium phosphate (alpha-TCP)/dicalcium phosphate dibasic (DCPD)/tetracalcium phosphate monoxide (TeCP) cement was implanted in paste form into soft tissue (rate subcutaneous sockets) and bone tissue (defects in rabbit mandibles) to evaluate the setting behaviour of the cement and tissue responses to the cement. A histological study of the soft tissue implants revealed thin fibrous capsule formation, the appearance of multinucleated giant cells on and close to the cement surface, and small clusters of the cement near the main part of the set cement which were formed by the migration of the paste while setting. X-ray diffraction (XRD) analysis of the implanted cement showed peaks for hydroxyapatite (HA) which increased as the implant period increased. Histology and microradiography of the bone tissue implants showed well-set cement without migration, active bone formation around the cement and direct bone union to it. However, the cement disappeared from the implant site in 4 of 16 specimens where intense bleeding seemed to wash away the implants while setting. From the results of the present study, we concluded that the cement is well tolerated, especially by bone tissue. This may be related to the fact that the cement sets producing HA. The cement is a promising material as a bone substitute; however, there is a problem of migration while setting in soft tissue and of exclusion from the bone defects by intense bleeding.


Asunto(s)
Cementos para Huesos , Fosfatos de Calcio , Hidroxiapatitas , Animales , Materiales Biocompatibles , Mandíbula/citología , Fagocitosis , Prótesis e Implantes , Conejos , Ratas , Ratas Wistar , Factores de Tiempo , Difracción de Rayos X
10.
Biomaterials ; 19(7-9): 701-6, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-9663743

RESUMEN

Calcium phosphate cement consisting of alpha-tricalcium phosphate (alpha-TCP), dicalcium phosphate dibasic (DCPD) and tetracalcium phosphate monoxide (TeCP) was implanted into surgically created full-thickness defects in the cranial bone (bone defect experiment) and directly onto the cranial bone under the periosteum (augmentation experiment). Three months after the implantation, the implants were retrieved with the surrounding tissues and studied histologically and micrographically to evaluate if the cement can be used as a cranioplasty and skeletal augmentation material. In the bone defect experiment, successful reconstruction of the defect was seen in 8 out of 12 specimens. Four specimens, where bleeding control was difficult at the time of implantation, showed partial loss of the cement. Histological and microradiographic studies of the successfully implanted cement revealed that new bone surrounded the implant nearly completely and united directly with the cement surface. In the augmentation experiment, the augmented area maintained the hemispherical shape and was connected tightly with the host bone. Histology and microradiography demonstrated that new bone formation was seen in the gap between the cement and the host bone, and on the outer surface (periosteum side) of the cement at the edge of the implant. From this preliminary short-term study, it could be concluded that the cement is a promising material for cranioplasty and skeletal augmentation with indications that it has good osteoconductivity.


Asunto(s)
Cementos para Huesos , Fosfatos de Calcio , Craneotomía/métodos , Cráneo/cirugía , Animales , Periostio/cirugía , Conejos , Cráneo/citología , Factores de Tiempo
11.
Neurosurgery ; 39(1): 174-7; discussion 177-8, 1996 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8805156

RESUMEN

OBJECTIVE AND IMPORTANCE: Intracranial giant aneurysms have been considered to grow by recurrence of intramural hemorrhage of the aneurysmal wall. However, it remains uncertain whether rupture of giant aneurysms is brought about by the same mechanism that causes the rupture of smaller saccular aneurysms. It is also unclear whether intramural hemorrhage is correlated with the rupture of giant aneurysms. CLINICAL PRESENTATION: A 67-year-old woman was admitted with symptoms of gait disturbance and dementia. Computed tomographic scans revealed a large mass located in the prepontine region and extending into the third ventricle as well as moderate dilatation of the lateral ventricles. Angiography demonstrated a giant basilar tip aneurysm and multiple aneurysms located in the bilateral anterior and middle cerebral arteries. INTERVENTION: Ventriculoperitoneal shunting was scheduled, but subarachnoid and intraventricular hemorrhage occurred and the patient died. Computed tomographic scans, performed immediately before the disastrous hemorrhage, displayed intramural hemorrhage in the wall of the giant basilar tip aneurysm. Ventricular drainage was performed, but the patient died. CONCLUSION: It seems probable that intramural hemorrhage of the aneurysmal wall may cause both the growth and rupture of intracranial giant aneurysms.


Asunto(s)
Aneurisma Roto/diagnóstico , Arteria Basilar , Hemorragia/diagnóstico , Aneurisma Intracraneal/diagnóstico , Músculo Liso Vascular , Hemorragia Subaracnoidea/diagnóstico , Anciano , Aneurisma Roto/patología , Arteria Basilar/patología , Angiografía Cerebral , Ventrículos Cerebrales/patología , Resultado Fatal , Femenino , Hemorragia/patología , Humanos , Aneurisma Intracraneal/patología , Imagen por Resonancia Magnética , Músculo Liso Vascular/patología , Hemorragia Subaracnoidea/patología , Tomografía Computarizada por Rayos X
12.
J Neurosurg ; 95(4): 710-3, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11596968

RESUMEN

The authors describe a case of glioblastoma multiforme (GBM) associated with previous gamma knife radiosurgery for a cerebral arteriovenous malformation (AVM). A 14-year-old boy had undergone radiosurgery for an AVM, which was performed using a 201-source 60Co gamma knife system at another institution. The maximum and margin radiation doses used in the procedure were 40 and 20 Gy, respectively. One year after radiosurgery, the patient noticed onset of mild left hemiparesis due to radiation necrosis. Six and one-half years after radiosurgery, at the age of 20 years, the patient experienced an attack of generalized tonic-clonic seizure. Magnetic resonance (MR) imaging revealed the existence of a brain tumor in the right parietal lobe. The patient underwent an operation and the histological diagnosis of the lesion was GBM. Ten months following the operation, that is, 99 months postradiosurgery, this patient died. To the best of the authors' knowledge, this is the first reported case of a neoplasm induced by radiosurgery for an AVM and the second case in which it occurred following radiosurgery for intracranial disease.


Asunto(s)
Neoplasias Encefálicas/etiología , Glioblastoma/etiología , Malformaciones Arteriovenosas Intracraneales/cirugía , Neoplasias Inducidas por Radiación , Lóbulo Parietal , Radiocirugia/efectos adversos , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/cirugía , Angiografía Cerebral , Preescolar , Terapia Combinada , Resultado Fatal , Glioblastoma/diagnóstico , Glioblastoma/patología , Glioblastoma/cirugía , Humanos , Malformaciones Arteriovenosas Intracraneales/diagnóstico por imagen , Masculino , Neoplasias Inducidas por Radiación/diagnóstico , Neoplasias Inducidas por Radiación/patología , Neoplasias Inducidas por Radiación/cirugía
13.
Neurol Res ; 23(8): 875-80, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11760881

RESUMEN

The aim of the present study was to investigate whether immediate ischemia is more harmful to the brain than progressive ischemia. To do so, we examined the correlation between the degree and the process of ischemia using hypobaric hypotension technique, which was used to reduce systemic blood pressure acutely or progressively below the lower threshold of CBF regulation, in rat brain. In Wistar rats (n = 21), global ischemia using bilateral carotid arteries occlusion coupled with hypobaric hypotension was induced by lowering mean arterial blood pressure (MABP) progressively to 55, 45 and 35 mmHg or immediately to 35 mm Hg. Local cerebral blood flow (ICBF) by laser Doppler (LD) flowmetry and tissue hemoglobin oxygen saturation (HbSO2) by a microspectrophotometric method were measured at 25 corresponding locations using a 'scanning' technique which employs a computer-controlled micromanipulator. Regional CBF (rCBF) and rHbSO2 were determined by calculation of the median value from the 25 ICBF and IHbSO2 data. In the 'progressive' group, rCBF and rHbSO2 decreased gradually and reached 12.2 +/- 15.8 LD-units and 44.9% +/- 13.4% at 35 mm Hg of MABP, respectively. In the 'immediate' group, both parameters dropped suddenly to 7.86 +/- 10.6 LD-units (p < 0.01 vs. CBF of the progressive group) and 22.5% +/- 15.5% (p < 0.001 vs. tissue HbSO2 of the progressive group) from the control at 35 mmHg. These data suggested that cerebral ischemia is better tolerated if it is induced gradually. CBF recorded by LD-scanning technique and HbSO2 value by microspectrophotometric method correlated well in the ischemic condition, indicating that HbSO2 can be preserved if CBF is decreased gradually.


Asunto(s)
Isquemia Encefálica/metabolismo , Isquemia Encefálica/fisiopatología , Encéfalo/metabolismo , Circulación Cerebrovascular , Oxígeno/metabolismo , Animales , Encéfalo/irrigación sanguínea , Hipotensión/metabolismo , Hipotensión/fisiopatología , Flujometría por Láser-Doppler , Masculino , Oxihemoglobinas/metabolismo , Ratas , Ratas Wistar
14.
J Pharm Sci ; 87(4): 448-52, 1998 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-9548897

RESUMEN

The effects of various protease inhibitors on the stability of leucine enkephalin (Leu-Enk) and [D-Ala2,D-Leu5] enkephalin (DADLE) were investigated, and the permeability of these peptides was also examined in an in vitro Ussing chamber. Captopril, thiorphan, bacitracin, bestatin, puromycin, amastatin, and sodium glycocholate (Na-GC) were chosen as protease inhibitors. Regional differences in the stability of Leu-Enk and DADLE were observed, and the rank order of the stability of these peptides was colon > duodenum > ileum > jejunum. Na-GC, amastatin, and puromycin were effective protease inhibitors for improving the stability of these peptides, although captopril and thiorphan did not improve the stability of Leu-Enk. In the transport studies, Leu-Enk did not cross the intestinal membrane in the absence of protease inhibitors, but its transport was improved in the presence of Na-GC. In addition, Na-GC, amastatin, and puromycin improved the permeability of DADLE in both jejunum and colon, while the permeability of DADLE was not improved by the addition of captopril, thiorphan, and bestatin. Furthermore, the permeability of 6-carboxyfluorescein, a poorly absorbable and stable compound, was also improved in the presence of Na-GC and bacitracin at a concentration of 10 mM. These findings indicated that amastatin, puromycin, and Na-GC at a concentration of 0.5 mM might increase the permeability of DADLE due to the improved stability of DADLE in the donor site. However, Na-GC and bacitracin at a concentration of 10 mM had absorption-enhancing activities which might be also related to the enhanced permeability of DADLE across the intestinal membrane.


Asunto(s)
Leucina Encefalina-2-Alanina/farmacocinética , Encefalina Leucina/farmacocinética , Intestinos/efectos de los fármacos , Inhibidores de Proteasas/farmacología , Animales , Permeabilidad de la Membrana Celular/efectos de los fármacos , Estabilidad de Medicamentos , Técnicas In Vitro , Mucosa Intestinal/metabolismo , Masculino , Ratas , Ratas Wistar
15.
J Pharm Pharmacol ; 49(11): 1057-61, 1997 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9401937

RESUMEN

The permeation of ebiratide (H-Met(O2)-Glu-His-Phe-D-Lys-Phe-NH(CH2)8NH2), a novel ACTH analogue, across the intestinal mucosae has been examined by use of isolated intestinal membranes from rats in a modified Ussing chamber. Regional differences were observed in the permeation of ebiratide across intestinal membranes; the order of membrane permeability was jejunum > ileum > duodenum > colon. Overall, the permeation of ebiratide was relatively poor. The effects of various absorption enhancers were examined to increase the intestinal permeability to ebiratide. Sodium glycocholate and sodium caprate had no significant enhancing effect on the permeability of the jejunal membrane, but significantly enhanced the permeation of ebiratide through the colonic membrane. On the other hand, N-dodecyl-beta-D-maltopyramoside (LM) significantly enhanced the permeation of ebiratide through both jejunal and colonic membranes. In general, the absorption-enhancing effects of these agents were more predominant in the colon than in the jejunum. Membrane damage by the absorption enhancers was evaluated by measuring the amount of protein released from the intestinal membrane. It was found that all the absorption enhancers slightly increased the amount of protein released, but that the amounts of protein released in the presence of these enhancers were much less than in the presence of ethylenediaminetetraacetic acid (EDTA), used as a positive control. These findings suggest that the absorption enhancers, especially LM might be useful adjuvants for improving the intestinal absorption of peptide and protein drugs, including ebiratide.


Asunto(s)
Hormona Adrenocorticotrópica/análogos & derivados , Mucosa Intestinal/metabolismo , Fragmentos de Péptidos/farmacocinética , Hormona Adrenocorticotrópica/farmacocinética , Animales , Colagogos y Coleréticos/farmacología , Ácidos Decanoicos/farmacología , Ácido Glicocólico/farmacología , Absorción Intestinal/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Masculino , Permeabilidad , Proteínas/metabolismo , Ratas , Ratas Wistar
16.
J Pharm Pharmacol ; 51(11): 1241-50, 1999 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-10632081

RESUMEN

We have examined the in-vitro permeability characteristics of insulin in the presence of various absorption enhancers across rat intestinal membranes and have assessed the intestinal toxicity of the enhancers using an in-vitro Ussing chamber method. The absorption enhancing mechanism of n-lauryl-beta-D-maltopyranoside was studied also. The permeability of insulin across the intestinal membranes was low in the absence of absorption enhancers. However, the permeability was improved in the presence of enhancers such as sodium glycocholate and sodium deoxycholate in the jejunum, and sodium glycocholate, sodium deoxycholate, n-lauryl-beta-D-maltopyranoside, sodium caprate and ethylenediaminetetraacetic acid (EDTA) in the colon. Overall, the absorption enhancing effects were greater on the colonic membrane than on the jejunal membrane. The intestinal membrane toxicity of these enhancers was characterized using the release of cytosolic lactate dehydrogenase from the colonic membrane. A marked increase in the release of lactate dehydrogenase was observed in the presence of sodium deoxycholate and EDTA. The release of lactate dehydrogenase in the presence of these absorption enhancers was similar to that seen with sodium dodecyl sulphate (SDS), used as a positive control, indicating high toxicity of these enhancers to the intestinal membrane. In contrast, sodium glycocholate and sodium caprate caused minor releases of lactate dehydrogenase, similar to control levels, suggesting low toxicity. In addition, the amount of lactate dehydrogenase in the presence of n-lauryl-beta-D-maltopyranoside was much less than that seen with sodium deoxycholate, EDTA and SDS. Therefore, sodium glycocholate, sodium caprate and n-lauryl-beta-D-maltopyranoside are useful absorption enhancers due to their high absorption enhancing effects and low intestinal toxicity. To investigate the absorption enhancing mechanisms of n-lauryl-beta-D-maltopyranoside, the transepithelial electrical resistance (TEER), voltage clamp experiments and the circular dichroism spectra were studied. n-Lauryl-beta-D-maltopyranoside decreased the TEER values in a dose-dependent manner, suggesting that the enhancer may open the tight junctions of the epithelium, thereby increasing the permeability of insulin via a paracellular pathway. This speculation was supported by the findings that 20 mM n-lauryl-beta-D-maltopyranoside produced a greater increase in the paracellular flux rate than in the transcellular flux rate by the voltage clamp studies. Evaluating the circular dichroism spectra we found that insulin oligomers were not dissociated to monomers by the addition of n-lauryl-beta-D-maltopyranoside, but dissociation did occur with the addition of sodium glycocholate. Thus, the dissociation of insulin was not a major factor in the absorption enhancing effect of n-lauryl-beta-D-maltopyranoside. These findings provide basic information to select the optimal enhancer for the intestinal delivery of peptide and protein drugs including insulin.


Asunto(s)
Excipientes/farmacología , Excipientes/toxicidad , Hipoglucemiantes/farmacocinética , Insulina/farmacocinética , Absorción Intestinal/fisiología , Mucosa Intestinal/metabolismo , Maltosa/análogos & derivados , Algoritmos , Animales , Cromatografía Líquida de Alta Presión , Dicroismo Circular , Electrofisiología , Técnicas In Vitro , Mucosa Intestinal/citología , Mucosa Intestinal/patología , Masculino , Maltosa/farmacología , Maltosa/toxicidad , Técnicas de Placa-Clamp , Soluciones Farmacéuticas , Ratas , Ratas Wistar
17.
Surg Neurol ; 46(1): 55-61, 1996 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8677490

RESUMEN

BACKGROUND: Dissecting aneurysms of the vertebrobasilar artery have been increasingly reported. However, those of the anterior circulation are still rare lesions. Those confined to the anterior cerebral artery are extremely rare and their clinical features are not well known. CASE REPORT: Two cases of spontaneous dissecting aneurysm of the anterior cerebral artery are described. Both patients are middle-aged males and presented with ischemic attacks, although they were lacking any factors correlated to atherosclerosis. Definite diagnosis was made by angiography, which demonstrated characteristics of dissecting aneurysm, such as "double lumen" and "string sign." Serial angiography was performed and revealed dynamic changes during the time course. Nonsurgical therapy was utilized and both patients achieved good recovery. CONCLUSION: Most of the dissecting aneurysms confined to the anterior cerebral artery present with ischemic attacks. Although their etiology remains uncertain, such aneurysms may be a potent cause of occlusive diseases of the anterior cerebral artery, especially in relatively young males lacking any factors correlated to atherosclerosis.


Asunto(s)
Disección Aórtica/diagnóstico , Disección Aórtica/fisiopatología , Arterias Cerebrales/fisiopatología , Adolescente , Adulto , Angiografía Cerebral , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Arteria Vertebral/fisiopatología
18.
Int J Oral Maxillofac Surg ; 24(5): 356-60, 1995 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-8627102

RESUMEN

Between 1985 and 1992, 13 patients were treated for delayed lymph-node metastases that developed after obtaining control of primary lesions of the tongue. These lesions were treated primarily by radiotherapy or surgical resection; cervical metastases were treated mainly by delayed radical neck dissection (RND). Seven of the 13 patients survived with no evidence of recurrence. The other six patients developed tumors in the neck, and five of these patients died due to uncontrollable disease. In all but one patient, recurrence appeared between the site of the primary lesion and the region of RND, the oral floor and/or the parapharyngeal space. None of the patients with recurrence received radiotherapy in the area between the primary lesion and the site of RND. In contrast, there was no recurrence in patients who received external irradiation to the primary lesion and upper cervical lymph nodes. This review emphasizes the need to direct more attention to the area between the site of the primary lesion and the regional lymph nodes in patients receiving treatment for delayed metastases associated with small carcinomas of the tongue.


Asunto(s)
Carcinoma de Células Escamosas/secundario , Metástasis Linfática/patología , Neoplasias de la Lengua/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Braquiterapia , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirugía , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática/radioterapia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/cirugía , Estudios Retrospectivos , Tasa de Supervivencia
19.
Anal Sci ; 17(5): 599-604, 2001 May.
Artículo en Inglés | MEDLINE | ID: mdl-11708139

RESUMEN

A simple electrochemical method for estimating the antioxidant activity (AA) of flavonoids has been developed. The proposed method is based on a measurement of the half-wave potential (E1/2) of the first oxidation wave of flavonoids by using flow-through column electrolysis. At the same time, the lipid peroxidation (LPO) inhibiting effects of these flavonoids were determined. A quantitative structure-activity relationship was obtained to describe the AA of flavonoids: IC50(microM) = 30.36 + 151.50 E1/2 (V) -12.63 log P (r = 0.852), where IC50 represents the concentration for 50% inhibition of LPO, and P represents the octanol/water partition coefficient. This method is expected to be useful for the quick screening of flavonoid antioxidants, and evaluating the AA of flavonoid-containing foods and medicinal plants.


Asunto(s)
Antioxidantes/química , Flavonoides/química , Animales , Antioxidantes/farmacología , Electrólisis , Flavonoides/farmacología , Análisis de los Alimentos , Técnicas In Vitro , Peroxidación de Lípido/efectos de los fármacos , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/metabolismo , Oxidación-Reducción , Plantas Medicinales , Relación Estructura-Actividad Cuantitativa , Ratas
20.
Artículo en Inglés | MEDLINE | ID: mdl-9503446

RESUMEN

OBJECTIVE: We report alteration of the temporomandibular joint disk and the condyle position through the construction of a mandibular full-coverage occlusal appliance (often referred to as a disk repositioning appliance). STUDY DESIGN: Forty-five joints with displaced disks with reduction were available for the study. We assessed these joints for disk recapture and the change of disk position with insertion of the appliance using magnetic resonance imaging. RESULTS: Of the 41 joints that had a recaptured disk with insertion of the splint, 25 slid in a posterior direction, although the amount of movement was negligible. No disk slid posteriorly in the joints without splint capture. CONCLUSIONS: On the basis of our results, we conclude that many of the occasionally displaced disks might have moved backward with successful treatment involving a disk-repositioning splint. However, the amount of the movement was negligible.


Asunto(s)
Luxaciones Articulares/terapia , Ferulas Oclusales , Trastornos de la Articulación Temporomandibular/terapia , Adolescente , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Disco de la Articulación Temporomandibular/patología , Resultado del Tratamiento
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