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1.
J Eur Acad Dermatol Venereol ; 32(9): 1499-1506, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29430733

RESUMO

BACKGROUND: Psychological aspect and quality of life should be considered in treating patients with psoriasis. OBJECTIVE: We sought to ascertain which clinical characteristics including presence of exposed lesions are associated with impairment of health-related quality of life (HRQoL) in patients with psoriasis. METHODS: The EPI-PSODE study was a nationwide, multicenter, cross-sectional study conducted in Korea that included 1260 adult patients with psoriasis. In addition to clinical characteristics including presence of exposed lesions, data were collected using the Psoriatic Arthritis (PsA) Screening and Evaluation (PASE), Dermatology Life Quality Index (DLQI), MOS 36-Item Short-Form Health Survey (SF-36), Work Productivity and Activity Impairment Questionnaire Psoriasis (WPAI: PSO) and Medication Satisfaction Questionnaire (MSQ). RESULTS: Patients with a DLQI score > 5 (n = 990) were younger, had an earlier onset of psoriasis, scored higher on the Psoriasis Area and Severity Index (PASI), had higher body surface area (BSA) and had higher PASE scores than patients with DLQI ≤ 5 (n = 266). The group of patients with exposed lesions (n = 871) were younger and male predominance, earlier onset of psoriasis, longer disease duration, higher PASI/BSA score and a higher proportion with drinking and smoking history each than the group of patients without exposed lesions (n = 389). Presence of exposed lesions negatively influenced DLQI, 36-Item Short-Form Health Survey (SF-36) (mental component), presenteeism, total work productivity impairment and total activity impairment in the WPAI: PSO. In multiple regression model, PASI score was the only variable which was significantly associated with all HRQoL measures. Presence of exposed lesions was a significant factor affecting DLQI and SF-36 (mental). CONCLUSION: The presence of exposed lesions has a negative impact on quality of life, mental health and work productivity. Therefore, effective treatments are particularly needed for psoriasis patients with exposed lesions.


Assuntos
Psoríase/psicologia , Qualidade de Vida , Adulto , Idade de Início , Consumo de Bebidas Alcoólicas/epidemiologia , Artrite Psoriásica/diagnóstico , Superfície Corporal , Estudos Transversais , Eficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Presenteísmo , Psoríase/epidemiologia , República da Coreia/epidemiologia , Índice de Gravidade de Doença , Fatores Sexuais , Fumar/epidemiologia , Inquéritos e Questionários
2.
Asian-Australas J Anim Sci ; 28(12): 1729-35, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26580440

RESUMO

This study was conducted to evaluate the effect of medicinal plant by-products (MPB) supplementation to a total mixed ration (TMR) on growth, carcass characteristics and economic efficacy in the late fattening period of Hanwoo steers. Twenty seven steers (body weight [BW], 573±57 kg) were assigned to 3 treatment groups so that each treatment based on BW contained 9 animals. All groups received ad libitum TMR throughout the feeding trial until slaughter (from 24 to 30 months of age) and treatments were as follows: control, 1,000 g/kg TMR; treatment 1 (T1), 970 g/kg TMR and 30 g/kg MPB; treatment 2 (T2), 950 g/kg TMR and 50 g/kg MPB. Initial and final BW were not different among treatments. Resultant data were analyzed using general linear models of SAS. Average daily gain and feed efficiency were higher (p<0.05) for T1 than control, but there was no difference between control and T2. Plasma albumin showed low-, intermediate- and high-level (p<0.05) for control, T1 and T2, whereas non-esterified fatty acid was high-, intermediate- and high-level (p<0.05) for control, T1 and T2, respectively. Carcass weight, carcass rate, backfat thickness and rib eye muscle area were not affected by MPB supplementation, whereas quality and yield grades were highest (p<0.05) for T1 and T2, respectively. Daily feed costs were decreased by 0.5% and 0.8% and carcass prices were increased by 18.1% and 7.6% for T1 and T2 compared to control, resulting from substituting TMR with 30 and 50 g/kg MPB, respectively. In conclusion, the substituting TMR by 30 g/kg MPB may be a potential feed supplement approach to improve economic efficacy in the late fattening period of Hanwoo steers.

3.
Nutr Metab Cardiovasc Dis ; 22(12): 1054-60, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21764572

RESUMO

BACKGROUND AND AIMS: This study aimed to examine the association between an increased ratio of triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) and insulin resistance as well as to investigate the interactive effect of TG/HDL-C and waist circumference on insulin resistance in a rural Korean population. METHODS AND RESULTS: This study, employing a cross-sectional design, included 8411 participants from the Korean Genomic Rural Cohort Study. Levels of fasting insulin, lipid profiles and anthropometric data were assessed for all participants. Insulin resistance was defined as a value greater than the 75th percentile on the homeostasis model assessment of insulin resistance (HOMA-IR). The TG/HDL-C ratio was positively correlated with waist circumference, total cholesterol, low-density lipoprotein cholesterol (LDL-C), TG and HOMA-IR, and negatively correlated with HDL-C when the calculations were controlled for gender. In comparison with the lowest quartile group of TG/HDL-C (≤1.92 in men, ≤1.63 in women), the odds ratios (ORs) (95% confidence interval) for insulin resistance in the highest quartile group of TG/HDL-C (>4.90 in men, >3.93 in women) were 2.33 (1.72-3.16) in men and 2.16 (1.73-2.71) in women, after adjusting for multiple covariates including waist circumference. Following stratification of waist circumference into quartiles, the effect of TG/HDL-C on insulin resistance remained significant irrespective of the waist circumference quartile. CONCLUSION: The TG/HDL-C ratio was linearly associated with insulin resistance in a rural Korean cohort independently of waist circumference in both genders, albeit not interactive.


Assuntos
HDL-Colesterol/sangue , Resistência à Insulina , Triglicerídeos/sangue , Circunferência da Cintura , Idoso , Povo Asiático , Glicemia , Índice de Massa Corporal , Estudos Transversais , Jejum , Feminino , Homeostase/efeitos dos fármacos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , República da Coreia , População Rural
4.
Clin Exp Dermatol ; 35(6): 650-7, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19886962

RESUMO

BACKGROUND: Hyaluronan (HA), a major extracellular matrix component in epidermis, has been found to accumulate in the epidermis after disruption of the epidermal barrier; however, the precise mechanisms underlying this process are not yet clear. Alterations in the epidermal calcium gradient are an important signal for permeability-barrier homeostasis. Thus, we hypothesized that epidermal calcium-ions might regulate HA expression. AIM: To investigate whether changes in the epidermal calcium gradient and subsequent induction of cytokines regulate HA, HA synthase (HAS) and HA receptor (CD44) expression in mouse epidermis, and to clarify the mechanisms of HA induction. METHODS: Sonophoresis of 1.5 mmol/L Ca(2+)-containing gel or Ca(2+)-free gel was performed to manipulate the epidermal Ca(2+) content without disrupting the permeability barrier. We also manipulated the Ca(2+) gradient by tape-stripping with or without 2 h immersion in 1.2 mmol/L Ca(2+)-containing solutions. Next we inhibited cytokine activity using tumour necrosis factor (TNF)-alpha or interleukin (IL)-1 inhibitors before sonophoresis. Six hours after each treatment, the expression of HA, HAS and CD44 were analysed using reverse transcription PCR and immunohistochemical stains. RESULTS: Sonophoresis of Ca(2+)-free gel significantly increased HA, HAS3 and CD44 expression in epidermis and in tape-stripped skin. However, the inhibition of Ca(2+) decrease in the upper epidermis by sonophoresis of Ca(2+)-containing gel or immersion of barrier-disrupted skin into a Ca(2+)-containing solution attenuated these inductions. Specific inhibitors of TNF-alpha and IL-1 specific inhibitors also abolished the sonophoresis-induced expression of HA, HAS3 and CD44. CONCLUSIONS: These results suggest that modulations in epidermal calcium regulate HA and CD44 expression directly or via induction of cytokines.


Assuntos
Cálcio/metabolismo , Epiderme/metabolismo , Receptores de Hialuronatos/metabolismo , Ácido Hialurônico/metabolismo , Animais , Feminino , Interleucina-1/metabolismo , Camundongos , Camundongos Pelados , Fator de Necrose Tumoral alfa/metabolismo
5.
Acta Radiol ; 49(5): 580-8, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18568546

RESUMO

BACKGROUND: Acute inflammatory responses have been thought to play a central role in ischemia-reperfusion injury after acute ischemic stroke. Superparamagnetic iron oxide (SPIO) particles have been known to enable in-vivo monitoring of macrophage infiltration by magnetic resonance imaging (MRI) in the experimental ischemic rat brain. PURPOSE: To determine whether the accumulation of macrophages could be seen in vivo in a reperfusion animal model after focal cerebral ischemia using SPIO-enhanced MRI. MATERIAL AND METHODS: Thirty-four adult male rats were enrolled in this study. SPIO particles were injected into the rats at different time points after 1-hour transient occlusion of the middle cerebral artery, and three-dimensional (3D) T2*-weighted magnetic resonance (MR) images with a gradient-echo sequence were performed 24 hours later. Histochemical iron staining was compared with T2* signal abnormalities. RESULTS: At days 3 and 4 post-reperfusion, focal areas of signal loss indicating local accumulation of SPIO particles appeared in a part of the damaged brain. Areas of signal loss corresponded to local accumulation of iron-laden macrophages in histologic sections, and SPIO-induced signal loss indicated active macrophage transmigration into the reperfused brain. CONCLUSION: SPIO-enhanced MRI demonstrated through in-vivo monitoring that macrophages participate in reperfusion injury at early stages of injury development. SPIO-enhanced MRI could be a useful tool to examine the inflammatory mechanisms involved in reperfusion brain injury.


Assuntos
Óxido Ferroso-Férrico , Aumento da Imagem/métodos , Inflamação/diagnóstico , Ataque Isquêmico Transitório/diagnóstico , Imageamento por Ressonância Magnética/métodos , Traumatismo por Reperfusão/diagnóstico , Animais , Encéfalo/patologia , Encéfalo/ultraestrutura , Meios de Contraste/administração & dosagem , Modelos Animais de Doenças , Imageamento Tridimensional , Inflamação/etiologia , Ataque Isquêmico Transitório/complicações , Macrófagos/patologia , Macrófagos/ultraestrutura , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/etiologia , Fatores de Tempo
6.
Mol Endocrinol ; 8(4): 528-36, 1994 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7519724

RESUMO

TRH is known to stimulate the transcription of the TSH gene in pituitary cells. To examine TRH-responsive elements of the human TSH alpha-subunit gene, we have used transient transfection of GH3 rat pituitary tumor cells. Using this system, TRH treatment stimulated expression of a reporter gene containing 846 base pairs from the 5'-flanking region of the human glycoprotein hormone alpha-subunit gene linked to luciferase. Analysis of 5'-deletions of the alpha-subunit sequence revealed that at least two DNA regions with upstream limits between positions -223 to -190 and positions -151 to -135 are important for regulation by TRH. The more proximal region includes a previously defined cAMP-response element (CRE) while the more upstream region contains an element with sequence similarity to the binding site for the pituitary transcription factor, Pit-1. The TRH responsiveness of each individual region was tested by inserting fragments upstream of a thymidine kinase-luciferase reporter gene. The -151 to -100 region had basal enhancer activity and permitted a 3.4-fold response to TRH. The -223 to -168 region did not permit a TRH response, but possessed basal enhancer activity. The combination of both regions resulted in a 5-fold stimulation by TRH. To assess the contributions of different signal transduction pathways, various combinations of treatments were examined. Combined treatment with TRH and forskolin led to an additive activity. Treatment with TRH plus phorbol 12-myristate-13-acetate resulted in the same level of reporter gene activity as with either agent alone.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
AMP Cíclico/fisiologia , DNA/genética , Elementos Facilitadores Genéticos , Regulação da Expressão Gênica/efeitos dos fármacos , Genes/efeitos dos fármacos , Subunidade alfa de Hormônios Glicoproteicos/genética , Sequências Reguladoras de Ácido Nucleico , Hormônio Liberador de Tireotropina/farmacologia , Animais , Sequência de Bases , Sítios de Ligação , Cálcio/farmacologia , Colforsina/farmacologia , Sequência Consenso , DNA/metabolismo , Proteínas de Ligação a DNA/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Subunidade alfa de Hormônios Glicoproteicos/biossíntese , Humanos , Dados de Sequência Molecular , Neoplasias Hipofisárias/patologia , Ratos , Proteínas Recombinantes de Fusão/biossíntese , Deleção de Sequência , Acetato de Tetradecanoilforbol/farmacologia , Tireotropina/biossíntese , Fator de Transcrição Pit-1 , Fatores de Transcrição/metabolismo , Células Tumorais Cultivadas
7.
J Invest Dermatol ; 113(2): 189-95, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10469302

RESUMO

Disruption of the epidermal permeability barrier causes an immediate loss of the calcium gradient, and barrier recovery is parallel with the restoration of the calcium gradient in the epidermis. Artificial restoration of the barrier function by occlusion with a water vapor-impermeable membrane abrogate the expected increase in lipid synthesis and retard the barrier recovery, as well as block the normalization of the epidermal calcium gradient. To clarify the long-term effects of occlusion after acute barrier perturbation, we studied the calcium distribution and epidermal keratinocytes response after occlusion with a water vapor-impermeable membrane immediately following tape stripping in the murine epidermis. Acute barrier disruption caused an immediate depletion of most calcium ions in the upper epidermis, obliterating the normal calcium gradient. When the skin barrier function was artificially corrected by occlusion, the return of calcium ions to the epidermis was blocked. After 2 h of air exposure or occlusion, the density of epidermal calcium precipitates remained negligible. The transitional cell layers appeared with occlusion, but not or negligibly with air exposure. By 6 h though, calcium precipitates could be seen, the density of the calcium precipitates with occlusion was more sparse than with air exposure. With the air exposure, the thickness of the stratum corneum had normalized and the calcium gradient nearly recovered to normal after 24 h. The longer the occlusion period, the greater was the increase of transitional cells. By 60 h of occlusion, the thickness of the stratum corneum had increased and the transitional cell layers had disappeared, in parallel with the calcium gradient which was almost normalized. These results show that prolonged occlusion of tape-stripped epidermis induced transitional cells and delayed the restoration of the epidermal calcium gradient, the stratum corneum was then restored, transitional cells having disappeared, in parallel with normalization of the epidermal calcium gradient.


Assuntos
Cálcio/metabolismo , Células Epidérmicas , Animais , Diferenciação Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Queratinócitos/química , Masculino , Camundongos , Camundongos Pelados , Curativos Oclusivos , Fatores de Tempo
8.
J Invest Dermatol ; 111(1): 39-43, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9665384

RESUMO

Iontophoresis increases the delivery of drugs across the stratum corneum, but the pathway by which ionized drugs transit the stratum corneum is unknown. In this study we examined the effect of iontophoresis on the skin barrier and the epidermal calcium gradient. Hairless mice were subjected to iontophoresis for 5-120 min and skin specimens were prepared for electron microscopy. Neither positive nor negative iontophoresis affected transepidermal water loss. Lacunar dilatation and partial distention of the intercellular layers of the stratum corneum were observed in rough proportion to applied time in iontophoresis skin as well as control skin. Additionally, using calcium capture cytochemistry, we demonstrated that both positive and negative iontophoresis caused the disappearance of the epidermal calcium gradient with marked decrease in calcium content in the upper epidermis. Positive iontophoresis was associated with increased calcium in the stratum basale and dermis, whereas negative iontophoresis increased calcium in the stratum corneum. Moreover, as previously shown after barrier disruption and sonophoresis, the decrease in calcium content in the upper epidermis was associated with an increase in lamellar body secretion and the build up of lamellar material at the stratum corneum-stratum granulosum interface. In conclusion, iontophoresis on the skin of hairless mice may induce the change of ionized molecules in the epidermis, as the loss of the calcium gradient, which causes the decrease of skin impedence, gives charged drugs the ability to cross the skin more easily. Also, the structural changes, such as lacunar dilatation, whether they result from hydration or occlusion, may help the transport of charged drugs across the stratum corneum.


Assuntos
Cálcio/metabolismo , Iontoforese , Pele/metabolismo , Animais , Epiderme/metabolismo , Camundongos , Camundongos Pelados
9.
J Invest Dermatol ; 117(1): 44-51, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11442748

RESUMO

There is evidence that the "acid mantle" of the stratum corneum is important for both permeability barrier formation and cutaneous antimicrobial defense. The origin of the acidic pH of the stratum corneum remains conjectural, however. Both passive (e.g., eccrine/sebaceous secretions, proteolytic) and active (e.g., proton pumps) mechanisms have been proposed. We assessed here whether the free fatty acid pool, which is derived from phospholipase-mediated hydrolysis of phospholipids during cornification, contributes to stratum corneum acidification and function. Topical applications of two chemically unrelated secretory phospholipase sPLA2 inhibitors, bromphenacylbromide and 1-hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol, for 3 d produced an increase in the pH of murine skin surface that was paralleled not only by a permeability barrier abnormality but also altered stratum corneum integrity (number of strippings required to break the barrier) and decreased stratum corneum cohesion (protein weight removed per stripping). Not only stratum corneum pH but also all of the functional abnormalities normalized when either palmitic, stearic, or linoleic acids were coapplied with the inhibitors. Moreover, exposure of intact murine stratum corneum to a neutral pH for as little as 3 h produced comparable abnormalities in stratum corneum integrity and cohesion, and further amplified the inhibitor-induced functional alterations. Furthermore, short-term applications of an acidic pH buffer to inhibitor-treated skin also reversed the abnormalities in stratum corneum integrity and cohesion, despite the ongoing decrease in free fatty acid levels. Finally, the secretory-phospholipase-inhibitor-induced alterations in integrity/cohesion were in accordance with premature dissolution of desmosomes, demonstrated both by electron microscopy and by reduced desmoglein 1 levels in the stratum corneum (shown by immunofluorescence staining and visualized by confocal microscopy). Together, these results demonstrate: (i) the importance of phospholipid-to-free-fatty-acid processing for normal stratum corneum acidification; and (ii) the potentially important role of this pathway not only for barrier homeostasis but also for the dual functions of stratum corneum integrity and cohesion.


Assuntos
Ácidos/metabolismo , Células Epidérmicas , Epiderme/metabolismo , Ácidos Graxos não Esterificados/biossíntese , Fosfolipídeos/metabolismo , Acetofenonas/farmacologia , Animais , Caderinas/metabolismo , Desmogleína 1 , Desmossomos/metabolismo , Inibidores Enzimáticos/farmacologia , Glicerofosfatos/farmacologia , Homeostase/efeitos dos fármacos , Homeostase/fisiologia , Concentração de Íons de Hidrogênio , Masculino , Camundongos , Camundongos Pelados , Inibidores de Fosfodiesterase/farmacologia , Fosfolipases A/antagonistas & inibidores , Fosfolipases A/metabolismo
10.
J Invest Dermatol ; 114(1): 64-70, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10620117

RESUMO

The aim of this study was to assess the effects of chemical and electrical modes of percutaneous penetration enhancement on the intercellular lipid lamellae of the stratum corneum. Hairless mice were treated with either oleic acid/propylene glycol and iontophoresis separately or together. Permeability barrier function was evaluated by measuring transepidermal water loss and correlated with the structure of stratum corneum intercellular lamellae, as evaluated by electron microscopy, using ruthenium tetroxide postfixation. Transepidermal water loss levels did not change following 1 h iontophoresis alone. In contrast, topical applications of 0.3 M oleic acid in propylene glycol for 1 h increased transepidermal water loss significantly. Moreover, the combined use of iontophoresis plus 0.3 M oleic acid for 1 h further increased transepidermal water loss at equivalent time points. Ultrastructural observations demonstrated both marked disorganization of the intercellular lipid lamellae, as well as the presence of distended lacunae within the stratum corneum in oleic acid/propylene glycol plus or minus iontophoresis-treated stratum corneum. This study provides direct evidence that the oleic acid/propylene glycol system can disrupt the stratum corneum lipid lamellar structures, and that coapplications of oleic acid with iontophoresis further enhance the effects of oleic acid. The synergy between chemical and physical enhancement may afford a new approach to promote transdermal drug delivery.


Assuntos
Ácido Oleico/farmacologia , Pele/efeitos dos fármacos , Pele/ultraestrutura , Animais , Epiderme/metabolismo , Iontoforese , Cinética , Masculino , Camundongos , Camundongos Pelados , Microscopia Eletrônica , Permeabilidade/efeitos dos fármacos , Pele/metabolismo , Perda Insensível de Água/efeitos dos fármacos
11.
J Invest Dermatol ; 121(4): 794-801, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14632198

RESUMO

To investigate the molecular organization and phase behavior of physiologic lipid mixtures that contain either newly synthesized pseudoceramide or type III synthetic ceramide, various analytical techniques were used. The phase transition temperatures detected in differential scanning calorimetry analysis were 51.19 and 50.52 for the pseudoceramide-containing physiologic lipid mixture and synthetic type III ceramide-containing lipid mixture, respectively. From the small angle XRD patterns, the multilamellar emulsion-pseudoceramide showed 11.5 nm and 7.61 nm lamellar phases, while the multilamellar emulsion-synthetic ceramide showed only a 7.61 nm lamellar phase. The nonceramide containing lipid mixture did not show any distinct repeat pattern. Lateral packing distances of multilamellar emulsion-pseudoceramide and multilamellar emulsion-synthetic ceramide were measured as 0.4119 and 0.4110 nm at 30, respectively, which indicated the presence of hexagonal lattice. On the contrary, non-multilamellar emulsion did not show any definite repeat pattern. Transmission electron microscopy observation showed nearly comparable lamellar structures in all of the tested emulsions compared to the structure of human stratum corneum intercellular lipid. Decrease of water contents resulted in phase transition into liquid phase for all the tested emulsions, whereas phase transition into orthorhombic phase was observed only in multilamellar emulsion-pseudoceramide. From these results, we concluded that the molecular organization of multilamellar emulsion-pseudoceramide was characterized as the lateral hexagonal phase and both the long and short periodicity lamellar phases, which showed structural similarity with the native human stratum corneum intercellular lipid.


Assuntos
Ceramidas/química , Emulsões/química , Anisotropia , Varredura Diferencial de Calorimetria , Humanos , Bicamadas Lipídicas/química , Microscopia Eletrônica , Microscopia de Polarização , Pele/química , Difração de Raios X
12.
J Mol Endocrinol ; 14(3): 313-22, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7669223

RESUMO

Our previous studies demonstrated that at least two DNA regions with upstream limits between positions -223 to -190 and positions -151 to -135 of the human TSH gene are important for transcriptional regulation by TRH in GH3 rat pituitary cells. The proximal region (-151 to -135 bp) including the cAMP-responsive element (CRE) was required for the induction of the TSH gene by TRH, while the distal region (-223 to -190 bp) containing an element similar to the binding site for the pituitary-specific transcription factor, Pit-1, was necessary to amplify the effects of TRH. To determine whether a pituitary-specific nuclear protein, in addition to the CRE-binding protein, is involved in the molecular mechanism of TRH regulation, a gel retardation assay and Southwestern blot analysis were performed on the distal region with GH3 cell nuclear extracts. GH3 extracts generated a distinct DNA-protein complex that was effectively eliminated in the presence of excess unlabelled DNA fragment, and TRH treatment increased the affinity of protein binding remarkably. Excess Pit-1 DNA-binding sequence from the rat prolactin gene inhibited formation of the complex, but mutation of the Pit-1 consensus sequence in the distal region did not eliminate the complex. In addition, Southwestern experiments showed that a 33 kDa nuclear protein present in GH3 cells bound to this region and its binding affinity was increased slightly 2 h after TRH treatment, with the maximal increase (fivefold) at 3 h, which was similar to the results when using gel retardation. Phosphatase treatment of nuclear protein also resulted in a loss of binding affinity. Taken together, these data indicate that the interaction of a pituitary-specific nuclear protein, identical or closely related to Pit-1, with the distal region may be involved in the TRH stimulation of human TSH gene expression.


Assuntos
Proteínas de Ligação a DNA/metabolismo , DNA/metabolismo , Tireotropina/genética , Fatores de Transcrição/metabolismo , Animais , Sequência de Bases , Sítios de Ligação , Regulação da Expressão Gênica/efeitos dos fármacos , Genes , Células HeLa , Humanos , Dados de Sequência Molecular , Neoplasias Hipofisárias/patologia , Ligação Proteica/efeitos dos fármacos , Ratos , Sequências Reguladoras de Ácido Nucleico , Hormônio Liberador de Tireotropina/farmacologia , Fator de Transcrição Pit-1 , Células Tumorais Cultivadas
13.
J Med Chem ; 33(6): 1553-61, 1990 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2342052

RESUMO

In order to study the structure-activity relationships of 2',3'-dideoxypurine nucleosides as potential anti-HIV agents, various 6-substituted purine analogues have been synthesized and examined in virus-infected and uninfected human peripheral blood mononuclear cells. N6-methyl-2',3'-dideoxyadenosine (D2MeA, 7a) was initially synthesized from adenosine via 2',3'-O-bisxanthate 3. As extension of this reaction to other N6-substituted compounds failed, a total synthetic method utilizing 2',3'-dideoxyribose derivative 9 was used for the synthesis of other purine nucleosides. An acid-stable derivative of N6-methyl-2',3'-dideoxyadenosine, 2'-fluoroarabinofuranosyl analogue 32 (D2MeFA), has been synthesized from the appropriate carbohydrate 24 by condensation with N6-methyladenine 23. Among these compounds, N6-methyl derivative (D2MeA) 7a proved to be one of the most potent antiviral agents. The order of potency for the 6-substituted compounds was NHMe greater than NH2 greater than Cl approximately N(Me)2 greater than SMe greater than OH approximately NHEt greater than SH greater than NHBn approximately H. The results suggest that a bulk tolerance effect at the 6-position of the 2',3'-dideoxypurine nucleoside may dictate the antiviral activity of these compounds. Acid-stable analogue 32 (D2MeFA) was found to be 20-fold less potent than the parent compound. Both D2MeA and D2MeFA were resistant to calf intestine adenosine deaminase. The presence of a fluorine atom in the carbohydrate moiety greatly increased stability to acid, making D2MeFA a potential orally active antiviral agent that could be useful for the treatment of retroviral infections in humans.


Assuntos
Antivirais , Didesoxiadenosina/análogos & derivados , Didesoxinucleosídeos/síntese química , HIV/efeitos dos fármacos , Didesoxinucleosídeos/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade
14.
J Med Chem ; 35(11): 1987-95, 1992 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-1597854

RESUMO

In order to study the structure-activity relationships of dioxolane nucleosides as potential anti-HIV agents, various enantiomerically pure dioxolane-pyrimidine nucleosides have been synthesized and evaluated against HIV-1 in human peripheral blood mononuclear cells. The enantiomerically pure key intermediate 8 has been synthesized in nine steps from 1,6-anhydro-D-mannose (1), which was condensed with 5-substituted pyrimidines to obtain various dioxolane-pyrimidine nucleosides. Upon evaluation of these compounds, cytosine derivative 19 was found to exhibit the most potent anti-HIV agent although it is the most toxic. The order of anti-HIV potency was as follows: cytosine (beta-isomer) greater than thymine greater than cytosine (alpha-isomer) greater than 5-chlorouracil greater than 5-bromouracil greater than 5-fluorouracil derivatives. Uracil, 5-methylcytosine, and 5-iodouracil derivatives were found to be inactive. Interestingly, alpha-isomer 20 showed good anti-HIV activity without cytotoxicity. As expected, other alpha-isomers did not exhibit any significant antiviral activity. (-)-Dioxolane-T was 5-fold less effective against AZT-resistant virus than AZT-sensitive virus.


Assuntos
Antivirais/síntese química , Citosina/análogos & derivados , Dioxolanos/síntese química , HIV-1/efeitos dos fármacos , Nucleosídeos de Pirimidina/síntese química , Antivirais/farmacologia , Antivirais/toxicidade , Citosina/síntese química , Citosina/farmacologia , Citosina/toxicidade , Dioxolanos/farmacologia , Dioxolanos/toxicidade , Humanos , Leucócitos Mononucleares/microbiologia , Conformação Molecular , Estrutura Molecular , Nucleosídeos de Pirimidina/farmacologia , Nucleosídeos de Pirimidina/toxicidade , Relação Estrutura-Atividade
15.
Eur J Pharmacol ; 306(1-3): 175-80, 1996 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-8813630

RESUMO

Effects of protein kinase C inhibitors, staurosporine and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride and protein tyrosine kinase inhibitors, genistein, tyrphostin and 2,5-dimethylcinnamate on the neutrophil responses stimulated by immunoglobulin G (IgG), complement C5a or platelet-activating factor were studied. After receptor binding, the role of protein kinase C and protein tyrosine kinase in the stimulation of neutrophil responses, superoxide production and lysosomal enzyme release in degraded IgG-activated neutrophils may be similar to chemoattractant-stimulated cells. In contrast to complement C5a or platelet-activating factor, protein tyrosine kinase appears to play an important role in the regulation of intracellular Ca2+ mobilization in neutrophils activated by degraded IgG rather than by protein kinase C.


Assuntos
Imunoglobulina G/metabolismo , Neutrófilos/efeitos dos fármacos , Proteína Quinase C/antagonistas & inibidores , Proteínas Tirosina Quinases/antagonistas & inibidores , Explosão Respiratória/efeitos dos fármacos , Animais , Cálcio/metabolismo , Bovinos , Genisteína , Humanos , Isoflavonas/farmacologia , Lisossomos/enzimologia , Neutrófilos/metabolismo , Proteína Quinase C/fisiologia , Proteínas Tirosina Quinases/fisiologia , Explosão Respiratória/fisiologia , Estaurosporina/farmacologia , Superóxidos/metabolismo
16.
Arch Dermatol ; 135(11): 1359-64, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10566834

RESUMO

OBJECTIVE: To evaluate the relief of acute pain and possible preventive effects on postherpetic neuralgia through the use of an epidural blockade in the acute stage of herpes zoster. DESIGN: Prospective, nonrandomized, comparative clinical trial. SETTING: A dermatologic clinic in a university hospital. PATIENTS: Sixty-five consecutive patients with pain due to acute herpes zoster were treated for a 7-day hospitalization period from July 1, 1996, through June 30, 1997. INTERVENTION: The consecutive patients were divided into 2 groups. Group A consisted of 30 patients who were seen from July 1, 1996, through December 31, 1996, and who were treated with intravenous acyclovir (5 mg/kg) for 7 days. Group B consisted of 35 patients who were seen from January 1, 1997, through June 30, 1997, and who were treated with intravenous acyclovir (5 mg/kg) and an epidural blockade for 7 days. The changes in the intensity of pain and the total duration of pain in both groups were assessed for 12 to 18 months. MAIN OUTCOME MEASURES: The number of days required for relief of pain and the total duration of pain. RESULTS: The mean +/- SD number of days required for relief of pain, which was rated on a scale of 100 (worst pain) to 0 (no pain), was significantly fewer in group B than in group A: it took 2.6 +/- 1.1 days to go from 100 to 50 on the relief-of-pain scale in group B, but 3.8 +/- 1.1 days in group A (P = .03), and 12.5 +/- 6.4 days to go from 100 to 10 in group B, but 20.1 +/- 14.6 days in group A (P = .04). The duration of late residual pain was significantly shorter in group B (5.9 +/- 5.8 days) than in group A (11.9 +/- 7.5 days) (P = .03). The total duration of pain was also significantly shorter in group B (18.5 +/- 9.3 days) than in group A (31.6 +/- 17.6 days) (P = .04). CONCLUSIONS: We believe that an epidural blockade combined with an antiviral agent is a very effective treatment modality for the pain of acute herpes zoster, and we recommend its use for the prevention of postherpetic neuralgia, with a view to shortening the total duration of pain, especially late residual pain.


Assuntos
Analgesia Epidural , Herpes Zoster/fisiopatologia , Bloqueio Nervoso , Neuralgia/tratamento farmacológico , Doença Aguda , Aciclovir/administração & dosagem , Aciclovir/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Anestésicos Locais/uso terapêutico , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Bupivacaína/uso terapêutico , Feminino , Seguimentos , Glucocorticoides/uso terapêutico , Humanos , Injeções Intravenosas , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Neuralgia/prevenção & controle , Medição da Dor , Estudos Prospectivos , Fatores de Tempo
17.
Arch Dermatol Res ; 293(6): 308-18, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11480591

RESUMO

Acute barrier disruption, regardless of the method of induction, depletes the stratum corneum intercellular lipids and this stimulates a series of lipid/ DNA synthesis activities which lead to barrier recovery. After barrier disruption by tape stripping, occlusion with a water vapor-impermeable membrane inhibits barrier repair. In this study, we investigated the changes in the murine epidermis after barrier perturbation by tape stripping and three different types of surfactants (Emalex NP-12, ENP-12; sodium dodecyl sulfate, SDS; benzalkonium chloride, BKC). To examine the effect of an artificial barrier, we covered the animals with a water vapor-impermeable membrane for 3 days following barrier disruption and then exposed them to the air for 2 days. The histological findings after occlusion or air exposure were similar. However, after air exposure for 2 days, the thickness of the epidermis including the stratum corneum and the stratum granulosum layers decreased to about half that of the epidermis after occlusion. Ultrastructural examination revealed obvious distortion of the lamellar bilayers within the stratum corneum interstices immediately after barrier disruption. After 3 days of occlusion, extensive disorganization was evident in the intercellular domain of the stratum corneum, whereas 2 days after removal of the occlusion, the normal basic unit structure of the lamellar bilayers had partially reappeared. Our findings provide evidence that the kinetic pattern of barrier repair and the morphological changes are similar after occlusion following barrier disruption regardless of the mechanism of disruption.


Assuntos
Epiderme/lesões , Epiderme/metabolismo , Ferimentos e Lesões/metabolismo , Animais , Epiderme/patologia , Masculino , Membranas Artificiais , Camundongos , Camundongos Pelados , Microscopia Eletrônica , Curativos Oclusivos , Permeabilidade , Ferimentos e Lesões/patologia
18.
Yonsei Med J ; 32(1): 74-8, 1991 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1652178

RESUMO

A case of adenoid cystic carcinoma of the prostate gland in a 38-year-old Korean man is described. Microscopically, variable patterns, that is, glandular, trabecular, cribriform and solid areas, were seen. The unusual location of this tumor in our patient highlights the ubiquitous distribution of this malignant neoplasm.


Assuntos
Carcinoma Adenoide Cístico/patologia , Neoplasias da Próstata/patologia , Adulto , Humanos , Masculino
19.
Yonsei Med J ; 33(3): 277-80, 1992 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-1292252

RESUMO

We report a case of multiple basal cell carcinoma associated with keratoacanthoma. A 65-year-old Korean female had suffered from multiple, variable-sized papules and nodules on the face for 20 years previous to treatment. She had no history of arsenic intake, irradiation, herb medication, or hereditable or preexisting dermatoses. Histopathologically, the tumors revealed typical findings of solid and adenoid types of basal cell carcinoma and keratoacanthoma.


Assuntos
Carcinoma Basocelular/patologia , Neoplasias Faciais/patologia , Ceratoacantoma/patologia , Neoplasias Cutâneas/patologia , Idoso , Carcinoma Basocelular/complicações , Neoplasias Faciais/complicações , Feminino , Humanos , Ceratoacantoma/complicações , Neoplasias Cutâneas/complicações
20.
Yonsei Med J ; 36(1): 97-101, 1995 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7740842

RESUMO

A case of alopecia universalis in a 45-year-old male was reported. The hair loss initiated on the eyebrows and progressed to the whole body, but the scalp hairs were well preserved. Histopathologic features of eyebrows were compatible findings with alopecia areata. This is a unique case of alopecia universalis without any involvement of scalp hairs.


Assuntos
Alopecia/patologia , Cabelo/patologia , Couro Cabeludo/patologia , Extremidades , Sobrancelhas/patologia , Genitália Masculina , Humanos , Masculino , Pessoa de Meia-Idade , Pele/patologia
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