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1.
Biosens Bioelectron ; 257: 116302, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38648705

RESUMO

This review article focuses on the recent printing technological progress in healthcare, underscoring the significant potential of implantable devices across diverse applications. Printing technologies have widespread use in developing health monitoring devices, diagnostic systems, and surgical devices. Recent years have witnessed remarkable progress in fabricating low-profile implantable devices, driven by advancements in printing technologies and nanomaterials. The importance of implantable biosensors and bioelectronics is highlighted, specifically exploring printing tools using bio-printable inks for practical applications, including a detailed examination of fabrication processes and essential parameters. This review also justifies the need for mechanical and electrical compatibility between bioelectronics and biological tissues. In addition to technological aspects, this article delves into the importance of appropriate packaging methods to enhance implantable devices' performance, compatibility, and longevity, which are made possible by integrating cutting-edge printing technology. Collectively, we aim to shed light on the holistic landscape of implantable biosensors and bioelectronics, showcasing their evolving role in advancing healthcare through innovative printing technologies.


Assuntos
Técnicas Biossensoriais , Próteses e Implantes , Técnicas Biossensoriais/instrumentação , Humanos , Eletrônica/instrumentação , Impressão Tridimensional , Desenho de Equipamento , Nanoestruturas/química , Atenção à Saúde/tendências
2.
J Dent ; 58: 48-53, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28161365

RESUMO

OBJECTIVES: To investigate the abrasive effect of the tongue on human enamel loss with and without a prior dietary acid challenge in an in situ model. METHODS: A single centre, single blind, randomly allocated, split mouth, four treatment regimen, in situ study in healthy adult volunteers was undertaken. Twenty four subjects wore two lower intra-oral appliances each fitted with 4 human enamel samples 6h/day for 15 days. The samples were treated with either 50ml orange juice or water for 5min ex vivo 4x/day; prior to being licked or not licked with the subject's tongue for 60s. There were 2 samples per group per subject. Surface loss was measured by contact profilometry. RESULTS: 23 subjects completed the study with no adverse events. The mean loss of enamel at 15days was: 0.08µm for water without licking, 0.10µm with water and licking; 1.55µm with orange juice alone, 3.65µm with orange juice and licking. In the absence of erosive challenge, licking had no detectable effect on enamel loss p=0.28. Without licking, orange juice had a highly significant effect on loss compared to water, p<0.001. Erosive challenge followed by licking more than doubled the loss of enamel p<0.001. CONCLUSIONS: When enamel was exposed to orange juice prior to licking, tissue loss as a result of tongue abrasion of the eroded surface was increased, and double that of the erosive challenge alone. Licking enamel with the tongue had no perceptible effect on enamel loss in the absence of the erosive challenge. CLINICAL SIGNIFICANCE: Enamel wear resulting from tongue abrasion on tooth surfaces softened by acid challenge, can be an unavoidable consequence of oral function. This may account for the pattern of erosive toothwear on palatal and occlusal tooth surfaces, reinforcing the importance of restricting the frequency of dietary acid challenge in susceptible individuals.


Assuntos
Citrus sinensis/efeitos adversos , Esmalte Dentário/efeitos dos fármacos , Sucos de Frutas e Vegetais/efeitos adversos , Língua/fisiopatologia , Abrasão Dentária/etiologia , Erosão Dentária/complicações , Adolescente , Adulto , Bebidas/efeitos adversos , Esmalte Dentário/patologia , Suplementos Nutricionais , Feminino , Humanos , Concentração de Íons de Hidrogênio , Masculino , Método Simples-Cego , Propriedades de Superfície , Fatores de Tempo , Erosão Dentária/patologia , Água , Adulto Jovem
3.
J Dent ; 57: 20-25, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27913279

RESUMO

OBJECTIVES: To compare the abrasive wear on human dentine in an in situ model associated with use of an experimental low abrasivity anti-sensitivity dentifrice containing 1% alumina and 5% sodium tripolyphosphate (STP) with an experimental ultra-low abrasivity non-alumina 5% STP dentifrice, a higher abrasivity daily-use whitening dentifrice, and water as controls. METHODS: This was a single-centre, single-blind, randomised, split-mouth, four-treatment, two-period, crossover in situ study in 29 healthy subjects. Subjects wore bilateral lower buccal appliances, each fitted with four dentine specimens. Study treatments were applied ex vivo (three times daily). Dentine loss was measured by non-contact profilometry after 5, 10 and 15days' treatment. RESULTS: All 29 subjects were included in the efficacy analysis. Significantly less dentine loss was associated with brushing with the low and ultra-low abrasivity dentifrices than with the higher abrasivity dentifrice at all timepoints (p<0.01). Brushing with ultra-low abrasivity dentifrice or water resulted in statistically significantly less dentine loss compared with brushing with the low abrasivity dentifrice at all timepoints (p<0.05). Dentine loss after brushing with ultra-low abrasivity dentifrice was not significantly different from brushing with water. CONCLUSIONS: The degree of dentine loss observed in this in situ model reflected the abrasivity of the study dentifrices. Brushing with low or ultra-low abrasivity STP-containing anti-sensitivity dentifrices resulted in significantly less dentine loss (equating to dentine wear) than with a higher abrasivity daily-use whitening dentifrice.


Assuntos
Esmalte Dentário/efeitos dos fármacos , Dentifrícios/uso terapêutico , Abrasão Dentária/tratamento farmacológico , Desgaste dos Dentes/tratamento farmacológico , Adulto , Óxido de Alumínio/farmacologia , Óxido de Alumínio/uso terapêutico , Estudos Cross-Over , Dentifrícios/química , Dentifrícios/farmacologia , Dentina/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polifosfatos/farmacologia , Polifosfatos/uso terapêutico , Método Simples-Cego , Fatores de Tempo , Erosão Dentária/tratamento farmacológico , Escovação Dentária/métodos , Cremes Dentais/farmacologia , Cremes Dentais/uso terapêutico , Adulto Jovem
4.
Clin Oral Investig ; 17(1): 195-203, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22315153

RESUMO

OBJECTIVES: The aim of the study was to determine in situ the relative abilities of two desensitising toothpastes to occlude dentinal tubules with or without acid challenge. MATERIALS AND METHODS: The study design was a single centre, randomised, split mouth crossover model examining four treatments over two periods. The primary outcome was the degree of occlusion proffered by two desensitising toothpastes [Sensodyne® Rapid Relief (8% strontium acetate, 1040 ppm sodium fluoride) and Colgate® Sensitive Pro-ReliefTM daily (8% arginine, 1450 ppm sodium monofluorophosphate)], a standard toothpaste (1450 ppm sodium fluoride) and water, after acid challenge. Healthy adult volunteers wore bi-lateral lower buccal appliances each with two dentine sections, receiving two treatments per study period. Samples were brushed twice a day with treatment, with two additional 3-min extra-oral acidic challenges applied ex vivo on days 3 and 4. A secondary outcome was the degree of occlusion attained in the absence of acid challenge. Examiners blinded to the study assessed occlusion by visual score of post-treatment scanning electron microscope images. RESULTS: All 28 participants completed the study. In the absence of acid challenge, occlusion scores for both desensitising toothpastes were similar and significantly better than control scores (p < 0.02). After acid challenge both desensitising toothpastes occluded more effectively than controls; however, occlusion scores for the strontium acetate paste were significantly greater than those of the arginine paste (p < 0.02). CONCLUSIONS: The occluding properties of the strontium acetate toothpaste were significantly more robust after acid challenge than those of the arginine toothpaste. CLINICAL RELEVANCE: Patients with hypersensitivity, regularly imbibing dietary acidic drinks, should be advised that Sensodyne® Rapid Relief provides robust tubule occlusion despite repeated acidic challenges.


Assuntos
Dessensibilizantes Dentinários/uso terapêutico , Dentina/efeitos dos fármacos , Cremes Dentais/uso terapêutico , Acetatos/uso terapêutico , Adulto , Arginina/uso terapêutico , Carbonato de Cálcio/uso terapêutico , Estudos Cross-Over , Dentina/ultraestrutura , Sensibilidade da Dentina/prevenção & controle , Feminino , Fluoretos/uso terapêutico , Seguimentos , Humanos , Concentração de Íons de Hidrogênio , Masculino , Microscopia Eletrônica de Varredura , Fosfatos/uso terapêutico , Método Simples-Cego , Fluoreto de Sódio/uso terapêutico , Estrôncio/uso terapêutico , Resultado do Tratamento , Água/química
5.
J Eur Acad Dermatol Venereol ; 16(4): 393-6, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12224701

RESUMO

We report three patients presented with clinical features of Ofuji's papuloerythroderma (pruritic erythematous papules and extensive erythema sparing all skin folds), however, showing histopathological findings of mycosis fungoides (Pautrier's microabscess, haloed lymphocytes, disproportionate epidermotropism, and wiry collagen bundles). One case was associated with plaque stage of mycosis fungoides and follicular mucinosis. T-cell receptor (TCR) gene rearrangement analysis in the lesional skin tissue demonstrated rearrangement of the gamma chain in all cases. HTLV-1 serology was negative for two patients who conducted HTLV-1 test. We think that Ofuji's papuloerythroderma might be a variant of early mycosis fungoides rather than secondary skin manifestations to certain cutaneous inflammatory diseases.


Assuntos
Dermatite Esfoliativa/patologia , Micose Fungoide/patologia , Dermatopatias Papuloescamosas/patologia , Neoplasias Cutâneas/patologia , Idoso , Biópsia por Agulha , Dermatite Esfoliativa/diagnóstico , Dermatite Esfoliativa/tratamento farmacológico , Diagnóstico Diferencial , Seguimentos , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Micose Fungoide/diagnóstico , Micose Fungoide/tratamento farmacológico , Terapia PUVA , Dermatopatias Papuloescamosas/diagnóstico , Dermatopatias Papuloescamosas/tratamento farmacológico , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/tratamento farmacológico , Resultado do Tratamento
6.
Proc Natl Acad Sci U S A ; 98(1): 361-6, 2001 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-11120886

RESUMO

It has been proposed recently that two types of GnRH receptors (GnRHR) exist in a particular species. Here we present data demonstrating that at least three types of GnRHR are expressed in a single diploid species, the bullfrog. Three different cDNAs, encoding distinct types of bullfrog GnRHR (bfGnRHR-1, bfGnRHR-2, and bfGnRHR-3), were isolated from pituitary and hindbrain of the bullfrog. BfGnRHR-1 mRNA was expressed predominantly in pituitary, whereas bfGnRHR-2 and -3 mRNAs were expressed in brain. The bfGnRHR-1, bfGnRHR-2, and bfGnRHR-3 proteins have an amino acid identity of approximately 30% to approximately 35% with mammalian GnRHRs and approximately 40% to approximately 50% with nonmammalian GnRHRs. Interestingly, bfGnRHR-2 has an 85% amino acid homology with Xenopus GnRHR. Less than 53% amino acid identity was observed among the three bfGnRHRs. All isolated cDNAs encode functional receptors because their transient expression in COS-7 cells resulted in a ligand-dependent increase in inositol phosphate production. Notably, all three receptors exhibited a differential ligand selectivity. For all receptors, cGnRH-II has a higher potency than mGnRH. In addition, salmon GnRH also has a strikingly high potency to stimulate all three receptors. In conclusion, we demonstrated the presence of three GnRHRs in the bullfrog. Their expression in pituitary and brain suggests that bfGnRHRs play an important role in the regulation of reproductive functions in the bullfrog.


Assuntos
Rana catesbeiana/genética , Receptores LHRH/classificação , Receptores LHRH/metabolismo , Sequência de Aminoácidos , Animais , Southern Blotting , Células COS , Clonagem Molecular , Primers do DNA , DNA Complementar/genética , Regulação da Expressão Gênica , Humanos , Fosfatos de Inositol/metabolismo , Ligantes , Dados de Sequência Molecular , Hipófise/química , Isoformas de Proteínas/química , Isoformas de Proteínas/classificação , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores LHRH/química , Receptores LHRH/genética , Rombencéfalo/química , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Especificidade por Substrato , Transfecção
7.
Mol Endocrinol ; 13(11): 1882-95, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10551782

RESUMO

The rat GnRH gene consists of four short exons (denoted 1, 2, 3, and 4) and three introns (A, B, and C). All three introns are spliced from the primary transcript, resulting in a mature mRNA. Northern blot and RT-PCR analyses showed that the GnRH primary transcript and its splicing intermediates are more prevalent than the mature GnRH mRNA in a variety of non-GnRH-producing tissues. To delineate the possible splicing mechanism of introns, an in vitro HeLa splicing system was used. Introns B and C were efficiently spliced, while intron A spanning between exon 1 and exon 2 was not. The retention of intron A was relieved when the 5'- and/or 3'-splice sites of intron A were point mutated based on the consensus sequence. The splicing activity was even more strengthened when a putative branchpoint site was moved to the upstream region of the pyrimidine tract of intron A. Intron A could be partially spliced when whole exons (2, 3, and 4) were linked up with intron A. There are two putative exonic splicing enhancers (ESEs) in exon 3 and exon 4. The ESE on exon 4 (ESE4) is much stronger than that on exon 3. The closer the ESE4 to the 3'-splice site of intron A, the better the splicing activity became. However, in the presence of the nuclear extract from GnRH neurons, there was an enhancement in the splicing activity notwithstanding the distance between ESE4 and 3'-splice site of intron A. These results suggest that the ESE4 functions as both the constitutive and regulated enhancer. Collectively, our study provides evidence that enhanced splicing of intron A by putative GnRH neuron-specific splicing factor(s) interacting with the ESEs is a prerequisite for mature GnRH synthesis.


Assuntos
Elementos Facilitadores Genéticos , Hormônio Liberador de Gonadotropina/genética , Neurônios/fisiologia , Splicing de RNA , Animais , Feminino , Perfilação da Expressão Gênica , Hormônio Liberador de Gonadotropina/metabolismo , Hipotálamo/química , Hipotálamo/fisiologia , Íntrons , Mutação , Área Pré-Óptica/fisiologia , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Transcrição Gênica
8.
J Neuroendocrinol ; 11(3): 195-201, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10201815

RESUMO

There exists evidence for the presence of ultrashort loop feedback circuits of gonadotropin-releasing hormone (GnRH) secretion in the hypothalamus. It is, however, uncertain whether a similar mechanism is involved in the regulation of GnRH gene expression in vivo. Furthermore, little is known about the regulation of GnRH receptor (GnRHR) expression in the brain. In the present study, we examined the regulation of GnRH and its receptor gene expression by GnRH in vivo. A GnRH agonist, [D-Ala6, des-Gly10]GnRH-ethylamide (des-Gly GnRH), was administered by intracerebroventricular (i.c.v.) injection via the lateral ventricle of ovariectomized and estradiol (OVX + E)-treated rats. The amounts of GnRH and GnRHR mRNA were measured in the preoptic area (POA) and posterior mediobasal hypothalamus (pMBH) micropunch samples from individual rat brain slices by respective competitive reverse transcription-polymerase chain reactions. The i.c.v. administration of des-Gly GnRH significantly decreased GnRH and GnRHR mRNA expression in a dose-and time-related manner: des-Gly GnRH (6 ng) suppressed GnRH and GnRHR mRNA expression within 2 h, and the suppression was maintained without significant variation until 8 h after treatment. Treatment with Antide, [N-Ac-D-Nal(2)1, pCl-D-Phe2, D-Pal(3)3, Lys(Nic)5, D-Lys(Nic)6, Lys(iPR)8, D-Ala10]GnRH (10 ng), a potent GnRH antagonist, did not alter GnRH mRNA expression, but prevented des-Gly GnRH-induced suppression of GnRH mRNA expression. Antide alone decreased GnRHR mRNA expression, but failed to alter agonist-induced suppression of GnRHR mRNA expression. These results demonstrate the existence of an ultrashort loop feedback mechanism for GnRH gene expression in the POA, along with homologous down-regulation of GnRHR mRNA expression in the pMBH.


Assuntos
Expressão Gênica , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/genética , Hipotálamo/metabolismo , Receptores LHRH/genética , Animais , Sequência de Bases , Primers do DNA , Feminino , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/farmacologia , Ratos , Ratos Sprague-Dawley
9.
Int J Radiat Oncol Biol Phys ; 43(2): 393-7, 1999 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-10030267

RESUMO

PURPOSE: The best prognosis in hepatocellular carcinoma (HCC) can be achieved with surgical resection; however, the number of resected cases are limited due to advanced lesions or associated liver disease. The purpose of this study was to investigate the efficacy and toxicity of a prospective trial of combined transcatheter arterial chemoembolization (TACE) and local radiotherapy (RT) in unresectable HCC. METHODS AND MATERIALS: Patients with histologically proven unresectable HCC due to either advanced lesions or associated cirrhosis were eligible. From March 1992 to August 1994, 30 patients were entered into this study. TACE was performed with Lipiodol (5 ml) and doxorubicin (Adriamycin ; 50 mg), followed by gelatin sponge particle (Gelfoam) embolization. Local RT was started within 7-10 days following TACE. Mean tumor dose was 44.0+/-9.3 Gy in daily 1.8 Gy fractions. Response was assessed by computerized tomography (CT) scan 4-6 weeks following completion of the treatment and then at 1-3-month intervals. Survival was calculated from the start of TACE using the Kaplan-Meier method. RESULTS: An objective response was observed in 19 patients, giving a response rate of 63.3%. Distant metastasis occurred in 10 patients, with 8 in the lung only and 2 in both lung and bone. Survival rates at 1, 2, and 3 years were 67%, 33.3%, and 22.2%, respectively. Median survival was 17 months. There were 6 patients surviving more than 3 years. Toxicity included transient elevation of liver function tests in all patients, fever in 20, thrombocytopenia in 4, and nausea and vomiting in 1. There was no treatment-related death. CONCLUSION: Combined TACE and local RT is feasible and tolerable. It gives a 63.3% response rate with median survival of 17 months. We feel that this regimen would be a new promising modality in unresectable HCC. Further study is required to compare the therapeutic efficacy of this regimen to TACE alone.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Adulto , Idoso , Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/secundário , Terapia Combinada , Meios de Contraste/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Esponja de Gelatina Absorvível/administração & dosagem , Hemostáticos/administração & dosagem , Humanos , Óleo Iodado/administração & dosagem , Cirrose Hepática/complicações , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/radioterapia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de Sobrevida
10.
J Neuroendocrinol ; 10(12): 911-8, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9870748

RESUMO

The present study was designed to investigate whether noradrenergic neurotransmission regulates the gene expression of gonadotropin-releasing hormone (GnRH) in the preoptic area and GnRH receptor in the pituitary. To this end, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4, 50 mg/kg), an intraperitoneal (i.p.) injection of selective noradrenergic neurotoxin, was administered 1 h before progesterone (1 mg) treatment in ovariectomized and estradiol-treated prepubertal rats. Treatment with DSP4 effectively blocked the progesterone-induced increase in hypothalamic noradrenaline content, but not dopamine content, indicating that DSP4 selectively inhibits noradrenergic neurotransmission. DSP4 significantly blocked progesterone-induced increase in serum luteinizing hormone (LH) concentrations as well as GnRH release from hypothalamic fragments incubated in vitro. DSP4 concomitantly down-regulated GnRH mRNA levels in the preoptic area, as determined by competitive reverse transcription-polymerase chain reaction. DSP4 also clearly down-regulated progesterone-induced GnRH receptor mRNA levels in the pituitary, whereas it failed to alter LHbeta mRNA levels. In summary, blockade of noradrenergic neurotransmission with DSP4 resulted in profound reductions of hypothalamic GnRH and pituitary GnRH receptor gene expression.


Assuntos
Adrenérgicos/farmacologia , Benzilaminas/farmacologia , Regulação para Baixo/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/genética , Receptores LHRH/genética , Esteroides/farmacologia , Animais , Benzilaminas/administração & dosagem , Dopamina/metabolismo , Estradiol/farmacologia , Feminino , Hormônio Liberador de Gonadotropina/metabolismo , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Injeções Intraperitoneais , Hormônio Luteinizante/sangue , Hormônio Luteinizante/genética , Neurotoxinas/farmacologia , Norepinefrina/metabolismo , Ovariectomia , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Progesterona/administração & dosagem , Progesterona/farmacologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley
11.
Endocrinology ; 136(6): 2587-93, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7750481

RESUMO

Using a competitive reverse transcription-polymerase chain reaction (RT-PCR), the amounts of GnRH receptor (GnRHR) transcript in a discrete nucleus micropunched from rat brain slices were determined. GnRHR transcript was highly expressed in anterior pituitary >> median eminence > posterior mediobasal hypothalamus (pMBH) > preoptic area (POA) but not in cortex and posterior pituitary, which were used as control tissues. To examine the effect of GABA on GnRHR transcript level, 10 nmol of muscimol, a GABA-A receptor agonist, or baclofen, a GABA-B receptor agonist, was microinjected into the lateral ventricle of ovariectomized rats. Two hours after an intraventricular injection, rats were decapitated. Blood was collected 1 h before and after drug administration and used for LH determination. Serum LH levels were significantly reduced by muscimol but not by baclofen within 2 h. The activation of GABA-A receptors with muscimol resulted in a significant inhibition in GnRHR transcript level in both the pMBH and POA but not in the pituitary. The activation of GABA-B receptors with baclofen, however, did not produce any effect on GnRHR transcript level in the pMBH and POA, as well as the pituitary. This experiment demonstrates for the first time that GABAergic neurotransmission, through GABA-A receptors, is involved in the regulation of GnRHR transcript level in the rat hypothalamus. This suggests that GABAergic neurotransmission regulates GnRHR gene expression in a coordinated, yet complex, fashion in the control of the neuroendocrine function of GnRH-LH axis.


Assuntos
Expressão Gênica/efeitos dos fármacos , Receptores LHRH/genética , Ácido gama-Aminobutírico/farmacologia , Animais , Baclofeno/farmacologia , Sequência de Bases , Encéfalo/metabolismo , Clonagem Molecular , Primers do DNA/genética , DNA Complementar/genética , Feminino , Agonistas de Receptores de GABA-A , Agonistas dos Receptores de GABA-B , Dados de Sequência Molecular , Muscimol/farmacologia , Mutação , Reação em Cadeia da Polimerase , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Distribuição Tecidual
12.
Neuroendocrinology ; 61(5): 486-92, 1995 May.
Artigo em Inglês | MEDLINE | ID: mdl-7617125

RESUMO

Although gamma-aminobutyric acid (GABA) is known to play an important role in the regulation of GnRH release from the hypothalamus, GABAergic action on hypothalamic GnRH gene expression is poorly understood. The present study aims to evaluate the effects of several GABAergic compounds on GnRH mRNA and serum LH levels at the times of LH surge induced by estrogen plus progesterone treatment in long-term ovariectomized adult rats. Animals received either aminooxyacetic acid (AOAA, an inhibitor of GABA catabolism, i.p.), muscimol (GABA-A type agonist, i.c.v.) or baclofen (GABA-B type agonist, i.c.v.) 2 h prior to sacrifice. GnRH mRNA in the preoptic/anterior hypothalamic area and serum LH levels were determined by Northern blot analysis and LH radioimmunoassay, respectively. All of three GABA mimetics blocked the LH surge induced by estrogen plus progesterone in a dose-dependent manner. However, inhibition of GABA catabolism with AOAA in a dose range of 10-100 mg/kg b.w. increased GnRH mRNA level by 30%. Activation of GABA-A receptor with muscimol at a low dose (5 nmol) but not at high doses (10 and 30 nmol) elevated GnRH mRNA levels by 60% over the control value. Activation of GABA-B receptor with baclofen augmented GnRH mRNA levels in a dose-dependent manner. These observations indicate that acute increase of GABAergic neurotransmission may differentially regulate the release and GnRH gene expression depending on its receptor subtypes.


Assuntos
Expressão Gênica , Hormônio Liberador de Gonadotropina/genética , Hipotálamo/metabolismo , Ovariectomia , Transmissão Sináptica/fisiologia , Ácido gama-Aminobutírico/fisiologia , Ácido Amino-Oxiacético/farmacologia , Animais , Baclofeno/farmacologia , Estradiol/farmacologia , Feminino , Hipotálamo Anterior/metabolismo , Muscimol/farmacologia , Área Pré-Óptica/metabolismo , Progesterona/farmacologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley
13.
Yonsei Med J ; 35(3): 252-9, 1994 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-7975734

RESUMO

Eighty-four patients with unresectable primary hepatocellular carcinoma due either to locally advanced lesion or to association with liver cirrhosis were treated with combined radiotherapy and hyperthermia from April 1988 to January 1991. Purpose of this study was to assess thermometry, response rate, toxicity, and survival in those patients. External radiotherapy was given with a total of 30.6 Gy/3.5 wks. Hyperthermia was given twice a week with a total of 6 treatment sessions using an 8 MHz radiofrequency capacitive type heating machine. Each hyperthermia session was started within 30 min following radiotherapy and continued for 30-60 min. Thermal data were analysed with maximum, minimum, and average temperatures of the tumors. Thermal mapping was also done. In thermometry results, maximum, minimum, and average temperatures of the tumors were 41.9 +/- 1.3 degrees C, 39.9 +/- 1.0 degrees C, and 40.8 +/- 0.9 degrees C, respectively. The fraction over 40 degrees C was 73 +/- 32% with a wide variation from 15% to 100%. Among 67 assessable patients, 27 patients showed tumor regression of more than 50% of the original tumor volume (40.3% response rate). Symptomatic improvement was observed in 78.6% of the patients. Acute toxicities during the treatment were mostly acceptable local pain (51.2%) and local fat necrosis (13.1%). The actuarial 1-year, 2-year, and 3-year survival rates were 44.8%, 19.7%, and 15.6%, respectively. Median survival was 6 months. In view of acceptable toxicities and the current rate of survival, further evaluation of combined treatment of radiotherapy and hyperthermia for unresectable hepatocellular carcinoma is warranted.


Assuntos
Carcinoma Hepatocelular/terapia , Hipertermia Induzida , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/radioterapia , Terapia Combinada , Feminino , Humanos , Neoplasias Hepáticas/radioterapia , Masculino , Pessoa de Meia-Idade , Indução de Remissão
14.
Brain Res ; 652(1): 177-80, 1994 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-7953720

RESUMO

Gonadotropin-releasing hormone (GnRH) is a major neural signal for hypothalamic control of gonadotropin secretion which in turn influences gonadal steroid synthesis. Progesterone (P) is known to affect release and content of GnRH. The action mechanism of P on GnRH mRNA level remains, however, to be resolved. Here we report that P augments GnRH mRNA level in hypothalamic tissues derived from ovariectomized, estradiol-treated adult rats. The stimulatory action of P was time-dependent and lasted at least for 9 h. When RU486, a P receptor antagonist, was administered 1 hr before P treatment, it clearly blocked the stimulatory action of P on GnRH mRNA level. These results strongly suggest that P regulates GnRH gene expression in the rat hypothalamus, presumably through the P receptor-mediated mechanism.


Assuntos
Estrogênios/farmacologia , Expressão Gênica/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/biossíntese , Hipotálamo/metabolismo , Ovariectomia , Progesterona/farmacologia , Animais , Feminino , Hormônio Liberador de Gonadotropina/genética , Hipotálamo/efeitos dos fármacos , Mifepristona/farmacologia , RNA Mensageiro/biossíntese , Ratos , Ratos Sprague-Dawley , Receptores de Progesterona/antagonistas & inibidores , Endonucleases Específicas para DNA e RNA de Cadeia Simples/metabolismo , Estimulação Química
15.
Neuroendocrinology ; 58(2): 234-9, 1993 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-7903433

RESUMO

We previously reported that GnRH gene expression was enhanced by progesterone (P) in the hypothalamus from ovariectomized and estrogen (OVX+E) treated immature rats. Recent studies indicate that excitatory amino acids may play an important role in the regulation of GnRH secretion and gene expression by steroids. Therefore the present study attempts to examine whether excitatory amino acids are involved in the P-induced GnRH gene expression and release in vitro. MK-801, an NMDA receptor antagonist or CNQX, a non-NMDA receptor antagonist, was administered to OVX+E+P-treated prepubertal female rats. GnRH mRNA was determined by Northern blot hybridization using 32P-labeled antisense RNA, and GnRH release in vitro from the hypothalamic fragments was monitored by GnRH radioimmunoassay. The administration of MK-801 (0.2 mg/kg) for 2 h significantly reduced the P-induced GnRH gene expression and release, whereas CNQX (0.4 mg/kg) had no effect. These results clearly indicate that excitatory amino acids by way of NMDA receptor are involved in the transsynaptic regulation of GnRH gene expression.


Assuntos
Maleato de Dizocilpina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/genética , Hipotálamo/efeitos dos fármacos , Progesterona/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , 6-Ciano-7-nitroquinoxalina-2,3-diona , Animais , Estrogênios/administração & dosagem , Feminino , Hipotálamo/metabolismo , Ovariectomia , Ovário/fisiologia , Quinoxalinas/farmacologia , Ratos , Ratos Sprague-Dawley , Transmissão Sináptica/efeitos dos fármacos
16.
Cancer Chemother Pharmacol ; 31 Suppl: S119-27, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1281042

RESUMO

Hepatocellular carcinoma is a major malignant disease in parts of Africa and Asia, including Korea. Surgical resection, which represents the best hope for cure, is limited by the extent of the disease and the high incidence of concurrent liver cirrhosis in Korea. We designed a phase II trial of combined external radiotherapy and hyperthermia for hepatocellular carcinoma that was unresectable due to either locally advanced lesions or associated liver cirrhosis so as to evaluate the efficacy and the safety of this combination regimen. This trial was performed at Yonsei Cancer Center between April 1988 and July 1988. External radiotherapy was delivered to a total dose of 3060 cGy/3.5 weeks. Hyperthermia was applied twice a week for a total of six treatment sessions using an 8-MHz radio-frequency capacitive-type heating device, i.e., Thermotron RF-8 and Cancermia. In all cases, hyperthermia was carried out within 30 min of the radiotherapy for a period of 30-60 min. The temperature in the tumor was measured by inserting a thermocouple into the tumor mass under ultrasonographic guidance in patients who did not have a bleeding tendency. The tumor response was assessed by CT scan after completion of the designed treatment. No complete response was obtained. However, a symptomatic improvement in abdominal pain was observed in 78.6% of cases and a partial response was achieved in 40% of the patients. The most important factor affecting the tumor response was the type of tumor (single massive, 71.4%; diffuse infiltrative, 20%; multinodular, 0; P < 0.005). The 1-year survival values determined for all patients and for the partial responders were 34% and 50%, respectively. The overall median duration of survival was 6.5 months. The median duration of survival for the partial responders was longer than that for the nonresponders (11 vs 5 months; P < 0.05). A mild degree of heat sensation, fever, first-degree burns of the skin, and nausea were observed as treatment-related adverse reactions. In conclusion, although this study is being continued, the results obtained thus for indicate that combined radiotherapy and hyperthermia seem to be effective in providing local tumor control and pain palliation in unresectable hepatocellular carcinoma while producing an acceptable level of toxicity.


Assuntos
Carcinoma Hepatocelular/terapia , Hipertermia Induzida , Neoplasias Hepáticas/terapia , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Terapia Combinada , Feminino , Humanos , Hipertermia Induzida/efeitos adversos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , alfa-Fetoproteínas/análise
17.
Yonsei Med J ; 32(2): 147-56, 1991 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-1659040

RESUMO

Four cases of hepatocellular carcinoma (HCC) were surgically resected following combined radiotherapy (RT) and hyperthermia (HT). Complete necrosis of the tumor without viable tumor cell was found in one case and extensive tumor necrosis was observed in the other three cases; the percentage of necrosis in the specimens were 40%, 70%, and 80%, respectively. Histologic assessment showed mainly coagulative necrosis in the tumor with focal liquefactive necrosis. Cystic dilatation of sinusoids was observed in both tumor and nontumorous normal liver tissue. Other changes in normal liver tissue were unremarkable except for infiltration of inflammatory cells, fatty change, and proliferation of the bile ducts which can usually be seen beyond the area where any space occupying lesions are present. It is concluded that combined radiotherapy and hyperthermia can significantly induce coagulative necrosis of hepatocellular carcinoma with nonsignificant minimal histologic changes in adjacent nontumorous liver tissue.


Assuntos
Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Hipertermia Induzida , Neoplasias Hepáticas , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/cirurgia , Terapia Combinada , Feminino , Humanos , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Necrose
18.
Yonsei Med J ; 30(1): 72-80, 1989.
Artigo em Inglês | MEDLINE | ID: mdl-2741475

RESUMO

Yonsei Cancer Center developed an RF(Radiofrequency) capacitive type heating device, GHT-RF8(Greenytherm) in cooperation with Green Cross Medical Corp., Korea in 1986 for the first time in Korea. Cooperative clinical studies of hyperthermia for the treatment of cancer using GHT-RF8 were conducted by Yonsei Cancer Center in collaboration with the Presbyterian Medical Center, Chonju, Korea. A total of forty patients with various histologically proven malignant tumors, including superficial (N = 13) and deep-seated tumors (N = 27), were treated with this newly developed heating device in conjunction with radiotherapy (N = 38) or chemotherapy (N = 2) at two different institutes between October 1986 and September 1987. These patients were locally far advanced or recurrent cases and considered to be refractory to conventional cancer treatment modalities. Radiotherapy was given in 200cGy per day, five times a week fractionations with a total tumor dose of 50-60Gy in 5-6 weeks. Within an hour after radiotherapy, the RF capacitive type of hyperthermia was given two times a week for a total of 4-10 treatment sessions and an attempt was made to maintain the tumor temperature at 41-45 degrees C for 30-60 minutes. Of forty patients treated, 14 patients with deep-seated tumors showed complete response and 20 patients showed partial response. The overall response rate was 85% (34 out of 40 patients) and only 6 patients showed no response. Complications from this treatment were mainly burns, superficial first degree burn in 2 cases, second degree in 4 cases and subcutaneous fat necrosis was observed in 2 cases.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Calefação/instrumentação , Hipertermia Induzida/instrumentação , Adolescente , Adulto , Idoso , Desenho de Equipamento , Feminino , Humanos , Hipertermia Induzida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Cintilografia , Tomografia Computadorizada por Raios X
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