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1.
Am J Ophthalmol Case Rep ; 33: 102007, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38374945

RESUMO

Purpose: In cases of macular hole (MH) that is difficult to close, including large, chronic, or highly myopic cases, the inverted internal limiting membrane (ILM) flap technique is often preferred and yields favorable surgical outcomes as compared to those yielded by conventional ILM peeling. However, no consensus exists on the optimal location and area for peeling and inverting the ILM, since multiple alternative methods have been reported alongside the original method. Several adverse effects associated with ILM peeling have been documented, including mechanical impairment of the retinal nerve fiber layer and decreased retinal sensitivity. Particularly, when glaucoma is concomitant, the retinal nerve fiber layer is fragile, raising concerns about a decrease in retinal sensitivity. Consequently, in patients with large MH alongside glaucoma, the goal is to select a procedure that maximizes the closure rate of the MH while minimizing any negative impact on glaucomatous visual field impairment. However, a technique for this purpose has not yet been validated. Observations: A woman in her 60s presented with visual impairment (20/50), metamorphopsia, and central scotoma of unknown onset in the right eye. A full-thickness MH accompanied by epiretinal proliferation (EP) was identified, with a minimum diameter of 506 µm. Although a retinal nerve fiber layer defect was not evident on ophthalmoscopy, thinning of the ganglion cell complex (GCC), extending from the superotemporal aspect of the optic disc, was observed on optical coherence tomography. Both microperimetry and static visual field testing revealed reduced retinal sensitivity in the thinned GCC areas. A pars plana vitrectomy combined with cataract surgery was performed to address her condition. The EP was embedded into the foveal cavity. On the basis of the microperimetry results, the ILM within the absolute scotoma region was peeled on the superotemporal side of the fovea to create a flap, which was then placed over the MH. A gas tamponade was applied, and the patient was maintained in a prone position postoperatively. The MH was successfully closed after the surgery, resulting in visual improvement (20/25). No decline in retinal sensitivity after the surgery was observed. Conclusions and importance: Determining the location and area of the inverted ILM flap on the basis of microperimetry results is a promising patient-tailored strategy for treating MH concomitant with glaucoma while preventing further ILM peeling-associated reduction in the retinal sensitivity.

2.
Ophthalmol Sci ; 3(3): 100305, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37214763

RESUMO

Purpose: To investigate the involvement of retinal traction in the pathogenesis of lamellar macular hole (LMH) and related diseases based on OCT-based consensus definition. Design: Retrospective, observational study. Participants: Seventy-two eyes with LMH, epiretinal membrane foveoschisis (ERM-FS), or macular pseudohole (MPH). Methods: To quantitatively evaluate the involvement and strength of retinal traction in their pathogenesis, retinal folds were visualized with en face OCT imaging, and the maximum depth of the parafoveal retinal folds (MDRF) was measured. Metamorphopsia was quantified by measuring the minimum visual angle of dotted lines needed to cause it to disappear using M-CHARTS (Inami). Main Outcome Measures: Maximum depth of retinal folds and M-CHARTS scores. Results: Of the 72 eyes, 26 were classified as having LMH, 25 as having ERM-FS, and 21 as having MPH. Parafoveal retinal folds were observed in 7 (26.9%) eyes with LMH, 25 (100%) with ERM-FS, and 21 (100%) with MPH. The MDRF (7.5 ± 17.6 µm) was significantly smaller in LMH than in ERM-FS (86.3 ± 31.4 µm) and MPH (74.5 ± 24.6 µm) (both P < 0.001), whereas no significant difference in MDRF between MPH and ERM-FS was observed (P = 0.43). A significant positive correlation between MDRF and M-CHARTS scores was observed in ERM-FS and MPH (P = 0.008 and 0.040, respectively) but not in LMH (P = 0.073). Conclusions: Retinal traction was significantly weaker in the LMH group than in the ERM-FS and MPH groups. The MDRF was significantly associated with the degree of metamorphopsia in the ERM-FS and MPH groups. These results provide insights into the diseases' pathophysiology and treatment strategy.

3.
Ophthalmol Sci ; 3(3): 100312, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37214764

RESUMO

Purpose: To investigate the relationship between retinal traction force and impairment of the inner retinal layer in patients with epiretinal membrane (ERM). Design: Nonrandomized, retrospective consecutive case series. Participants: Two hundred nine eyes of 201 patients with idiopathic ERM who underwent vitrectomy for idiopathic ERM were enrolled. Methods: Retinal folds caused by ERM were visualized using en face OCT, and the maximum depth of retinal folds within the parafovea (MDRF) was measured. Focal macular electroretinogram (ERG) was used to measure the amplitude and implicit time of each component for the ERM eyes and the normal fellow eyes. B-scan OCT images were used to measure the thicknesses of the inner nuclear layer (INL) and outer nuclear layer (ONL) + outer plexiform layer (OPL). Expression of α-smooth muscle actin (α-SMA) in surgically removed ERM specimens was quantified by reverse-transcription polymerase chain reaction. Main Outcome Measures: We analyzed the relationship between MDRF and the relative amplitudes of focal macular ERG (affected eye/fellow eye), the relationships between MDRF and the mean INL thickness and ONL+OPL thickness, comparison of INL thickness and ONL+OPL thickness for each area when cases were classified according to MDRF localization in the ETDRS chart, and the relationship between MDRF and the relative expression of α-SMA in the ERM specimens. Results: The MDRF significantly correlated with the relative amplitudes (affected eye/fellow eye) of b-waves and oscillatory potentials (r = -0.657, P = 0.015; r = -0.569, P = 0.042, respectively) and the mean INL thickness and ONL+OPL thickness (r = 0.604, P < 0.001; r = 0.210, P = 0.007, respectively). However, only the INL thickness progression rate was significantly correlated with the MDRF progression rate (r = 0.770, P < 0.001). On case stratification by localization of MDRF based on the ETDRS chart, in regions other than temporal regions, the INL thickness was significantly greater in regions with MDRF than in other regions. The MDRF significantly correlated with α-SMA expression in the ERM specimens (r = 0.555, P = 0.009). Conclusions: The findings suggest that ERM impairs the inner retinal layer in a traction force-dependent manner. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

4.
Jpn J Ophthalmol ; 67(4): 410-416, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37115483

RESUMO

PURPOSE: To investigate preoperative factors associated with simultaneous internal limiting membrane (ILM) peeling during epiretinal membrane (ERM) removal. STUDY DESIGN: Observational cross-sectional study. METHODS: We retrospectively reviewed 60 eyes with idiopathic ERM that underwent vitrectomy. The gap between the ERM and ILM was visualized using en face optical coherence tomography. The depth and width of the ERM-ILM gap at the initiation site of ERM removal were measured, and the relationship between preoperative factors including these parameters and simultaneous ILM peeling during ERM removal was investigated. RESULTS: The ILM was simultaneously peeled during ERM removal in 30 eyes, but not in the other 30 eyes. Age was significantly higher (P = 0.017) and the width of the ERM-ILM gap was significantly smaller (P < 0.001) in the simultaneous ILM peeling (+) group than in the simultaneous ILM peeling (-) group. Multivariate logistic regression analysis confirmed the width of the ERM-ILM gap as a significant negative predictor for simultaneous ILM peeling (odds ratio, 0.992; 95% confidence interval, 0.986-0.997; P = 0.003). Receiver operating characteristic curve analysis of the width of the ERM-ILM gap revealed that the optimal cutoff for predicting simultaneous ILM peeling was 187.1 µm. CONCLUSION: The small width of the ERM-ILM gap at the initiation site of ERM removal was significantly associated with simultaneous ILM peeling, indicating that the adhesion strength between the ERM and ILM at the initial ERM grasping site determines whether simultaneous ILM peeling will occur during ERM removal.


Assuntos
Membrana Epirretiniana , Humanos , Membrana Basal/cirurgia , Estudos Transversais , Membrana Epirretiniana/diagnóstico , Membrana Epirretiniana/cirurgia , Retina , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Vitrectomia/métodos
5.
Retina ; 42(4): 704-711, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34983900

RESUMO

PURPOSE: To establish an objective and quantitative biomarker of metamorphopsia in epiretinal membranes (ERMs) and determine the optimal timing for ERM surgery. METHODS: Retrospectively, 172 eyes with ERM were reviewed. Retinal folds because of tangential traction by ERM were visualized by en-face optical coherence tomography. The maximum depth of retinal folds (MDRF) within the parafovea was quantified. Metamorphopsia was quantified by M-CHARTS. The change in the distance between the retinal vessels after ERM surgery and the preoperative total depth of retinal folds between the vessels were quantified using en-face optical coherence tomography and optical coherence tomography angiography. RESULTS: Significant correlations were observed between preoperative MDRF and M-CHARTS scores before and at 6 months after surgery (r = 0.617 and 0.460, respectively; P < 0.001) and change in the distance between the retinal vessels after ERM surgery and preoperative total depth of retinal folds between the vessels (r = 0.471; P = 0.013). The preoperative MDRF values at which M-CHARTS scores were 0.5 before and 6 months after the surgery were 69 µm and 118 µm, respectively. CONCLUSION: The MDRF is an objective and quantitative biomarker of metamorphopsia in ERM. To maintain patients' quality of vision, ERM surgery may be performed when the preoperative MDRF ranges between 69 µm and 118 µm.


Assuntos
Membrana Epirretiniana , Biomarcadores , Membrana Epirretiniana/complicações , Membrana Epirretiniana/cirurgia , Humanos , Retina , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Transtornos da Visão/etiologia , Acuidade Visual , Vitrectomia/métodos
6.
Retina ; 40(5): 989-997, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-30649079

RESUMO

PURPOSE: To investigate the clinical course of submacular hemorrhage associated with ruptured retinal arterial macroaneurysm using swept-source optical coherence tomography. METHODS: This study included 23 eyes of 23 consecutive patients diagnosed with submacular hemorrhage associated with ruptured retinal arterial macroaneurysm. Cases underwent displacement of submacular hemorrhage (vitrectomy + subretinal injection of tissue plasminogen activator + air tamponade) and were followed up for 6 months after surgery. Localization of the preoperative hemorrhage and its effect on preoperative and postoperative best-corrected visual acuity, central retinal thickness, and continuity of the ellipsoid zone were measured. RESULTS: Macular intraretinal hemorrhage (IRH) was observed in 17 eyes (73.9%, IRH [+] group) and was not observed in 6 eyes (26.1%, IRH [-] group). The IRH (+) group showed worse postoperative best-corrected visual acuity values compared with the IRH (-) group (0.89 ± 0.47 in logarithm of the minimal angle of resolution units, Snellen equivalent 20/155 and 0.16 ± 0.23, 20/29, respectively; P < 0.01), smaller central retinal thickness values (97.7 ± 53.5 µm, 173.0 ± 32.3 µm, respectively; P < 0.01), and a higher rate of ellipsoid zone disruption (100%, 33.3%, respectively; P < 0.01). CONCLUSION: Patients with preoperative macular IRH showed lower postoperative visual acuity and worse macular contour after submacular hemorrhage displacement compared with patients without macular IRH.


Assuntos
Aneurisma Roto/complicações , Angiofluoresceinografia/métodos , Retina/patologia , Macroaneurisma Arterial Retiniano/complicações , Hemorragia Retiniana/diagnóstico , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Idoso de 80 Anos ou mais , Aneurisma Roto/diagnóstico , Feminino , Seguimentos , Fundo de Olho , Humanos , Masculino , Prognóstico , Macroaneurisma Arterial Retiniano/diagnóstico , Hemorragia Retiniana/etiologia , Estudos Retrospectivos
7.
Br J Pharmacol ; 153(7): 1388-98, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18246090

RESUMO

BACKGROUND AND PURPOSE: We previously demonstrated that chronic hyperinsulinaemia induced by drinking high levels of fructose augments adrenergic nerve-mediated vasoconstriction and suppresses vasodilatation mediated by calcitonin gene-related peptide (CGRP)-containing (CGRPergic) vasodilator nerves. In this study, the effects of pioglitazone on vascular responses induced by stimulation of adrenergic nerves, CGRPergic nerves and vasoactive agents were investigated in pithed rats given 15% fructose solution to drink (FDR). EXPERIMENTAL APPROACH: To assess the effect of pioglitazone on the altered vascular responsiveness in the hyperinsulinaemic state in vivo, changes in vascular responses to spinal cord stimulation (SCS) and intravenous bolus injections of noradrenaline, angiotensin II and CGRP were evaluated in pithed control rats and FDR either untreated or treated with pioglitazone. KEY RESULTS: In the pithed FDR, vasoconstrictor responses to SCS and to injections of noradrenaline and angiotensin II were significantly greater than those of pithed control rats. In pithed FDR with artificially increased blood pressure and blockade of the autonomic ganglia, the vasodilator responses to SCS and CGRP injection were significantly smaller than those of pithed control rats. Oral administration of pioglitazone to FDR for two weeks markedly decreased plasma levels of insulin, triglycerides and blood glucose. In FDR pioglitazone diminished the augmented vasoconstrictor responses to SCS, noradrenaline and angiotensin II, and ameliorated the decrease in vasodilator responses to SCS. CONCLUSIONS AND IMPLICATIONS: The present results suggest that pioglitazone improves not only insulin resistance, but also the dysfunctions in vascular control regulated by adrenergic and CGRPergic nerves in the hyperinsulinaemic state.


Assuntos
Hiperinsulinismo/tratamento farmacológico , Hipoglicemiantes/farmacologia , Tiazolidinedionas/farmacologia , Administração Oral , Angiotensina II/farmacologia , Animais , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Doença Crônica , Modelos Animais de Doenças , Hiperinsulinismo/fisiopatologia , Hipertensão/etiologia , Hipertensão/prevenção & controle , Insulina/sangue , Insulina/metabolismo , Resistência à Insulina , Masculino , Norepinefrina/farmacologia , Pioglitazona , Distribuição Aleatória , Ratos , Ratos Wistar , Triglicerídeos/sangue , Vasoconstrição/efeitos dos fármacos
8.
Neuroscience ; 150(3): 730-41, 2007 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-17950540

RESUMO

The present study was designed to investigate involvement of angiotensin II (Ang II) type 2 receptors (AT2 receptors) in restoration of perivascular nerve innervation injured by topical phenol treatment. Male Wistar rats underwent in vivo topical application of 10% phenol around the superior mesenteric artery. After phenol treatment, animals were subjected to immunohistochemistry of the third branch of small arteries, Western blot analysis of AT2 receptor protein expression in dorsal root ganglia (DRG) and studies of mesenteric neurogenic vasoresponsiveness. Ang II (750 ng/kg/day), nerve growth factor (NGF; 20 microg/kg/day) and PD123,319 (AT2 receptor antagonist; 10 mg/kg/day) were intraperitoneally administered for 7 days using osmotic mini-pumps immediately after topical phenol treatment. Losartan (AT1 receptor antagonist) was administered in drinking water (0.025%). Phenol treatment markedly reduced densities of both calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI) and neuropeptide Y (NPY)-LI-containing fibers. NGF restored densities of both nerve fibers to the sham control level. Coadministration of Ang II and losartan significantly increased the density of CGRP-LI-fibers but not NPY-LI-fibers compared with saline control. The increase of the density of CGRP-LI-fibers by coadministration of Ang II and losartan was suppressed by adding PD123,319. Coadministration of Ang II and losartan ameliorated reduction of CGRP nerve-mediated vasodilation of perfused mesenteric arteries caused by phenol treatment. The AT2 receptor protein expression detected in DRG was markedly increased by NGF. These results suggest that selective stimulation of AT2 receptors by Ang II facilitates reinnervation of mesenteric perivascular CGRP-containing nerves injured by topical phenol application in the rat.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Sistema Nervoso Entérico/fisiologia , Artéria Mesentérica Superior/inervação , Regeneração Nervosa/fisiologia , Receptor Tipo 2 de Angiotensina/metabolismo , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Western Blotting , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Sistema Nervoso Entérico/citologia , Gânglios Espinais/metabolismo , Imidazóis/farmacologia , Losartan/farmacologia , Artéria Mesentérica Superior/metabolismo , Fibras Nervosas/efeitos dos fármacos , Fibras Nervosas/metabolismo , Fator de Crescimento Neural/farmacologia , Regeneração Nervosa/efeitos dos fármacos , Neuropeptídeo Y/metabolismo , Norepinefrina/farmacologia , Fenol , Piridinas/farmacologia , Ratos , Ratos Wistar , Soluções Esclerosantes , Resistência Vascular/fisiologia , Vasoconstrição/efeitos dos fármacos , Vasoconstrição/fisiologia , Vasoconstritores/farmacologia
9.
Methods Find Exp Clin Pharmacol ; 25(7): 517-20, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-14571280

RESUMO

When guinea pig eosinophils were incubated with fenoterol, a beta2-agonist, for 120 min, not only desensitization of beta2-adrenoceptors but also hyperresponsiveness to phosphodiesterase (PDE) inhibitors, such as theophylline and rolipram, was observed. The fenoterol-induced beta2-adrenoceptor desensitization was not affected by pretreatment with either genistein, a broad-spectrum tyrosine kinase inhibitor, or PP2, a specific Src family tyrosine kinase inhibitor. On the other hand, both genistein and PP2 abolished the hyperresponsiveness to PDE inhibitors in beta2-adrenoceptor-desensitized eosinophils. These findings suggested that Src family tyrosine kinases play important roles in the hypersensitization of PDE to PDE inhibitors in beta2-adrenoceptor-desensitized eosinophils.


Assuntos
Agonistas Adrenérgicos beta/farmacologia , Eosinófilos/efeitos dos fármacos , Fenoterol/farmacologia , Inibidores de Fosfodiesterase/farmacologia , Receptores Adrenérgicos beta 2/efeitos dos fármacos , Quinases da Família src/fisiologia , Animais , Calcimicina/farmacologia , Degranulação Celular/efeitos dos fármacos , Peroxidase de Eosinófilo , Eosinófilos/enzimologia , Eosinófilos/fisiologia , Genisteína/farmacologia , Cobaias , Técnicas In Vitro , Ionóforos/farmacologia , Masculino , Peroxidases/metabolismo , Pirimidinas/farmacologia , Receptores Adrenérgicos beta 2/fisiologia , Fatores de Tempo
10.
Methods Find Exp Clin Pharmacol ; 25(3): 193-7, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12743623

RESUMO

The effects of [Arg(8)]-vasopressin (AVP) and related compounds on regional cerebral blood flow (rCBF) in the hippocampus were studied using conscious spontaneously hypertensive rats (SHR). rCBF in the hippocampus decreased gradually with age in proportion to an increase in mean blood pressure. Subcutaneous injection of AVP caused a dose-dependent increase in rCBF in the hippocampus. The effects of the metabolic fragments AVP4-9 and AVP4-8 on rCBF were relatively weak. OPC-31260, a vasopressin V(2) antagonist, antagonized the AVP-induced increase in rCBF in the hippocampus. Furthermore, subcutaneous injection of DDAVP, a V(2) agonist, increased rCBF in the hippocampus. On the other hand, the AVP-induced increase in rCBF in the hippocampus was not antagonized by OPC-21268, a vasopressin V(1) antagonist. Intracerebroventricular injection of AVP caused no significant changes in rCBF in the hippocampus, even at a dose of 10 ng/site.


Assuntos
Arginina Vasopressina/farmacologia , Circulação Cerebrovascular/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Vasoconstritores/farmacologia , Animais , Injeções Intraventriculares , Masculino , Ratos , Ratos Endogâmicos SHR
11.
Methods Find Exp Clin Pharmacol ; 24(5): 267-73, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12168502

RESUMO

The changes in membrane potential induced by compound 48/80 were studied using rat peritoneal mast cells. The mean resting membrane potential of rat mast cells was -12.3 +/- 0.7 mM. When compound 48/80 was added to the mast cells, the cells were degranulated approximately 120 sec after the addition of the drug, after which immediate depolarization occurred. Degranulation of mast cells was not observed, even under the depolarization or hyperpolarization conditions caused by the replacement of a high K+ medium or the removal of K+ from the medium, respectively. Under both conditions, when compound 48/80 was added to the mast cells, degranulation was observed. Abrupt and marked depolarization was induced 30-60 sec after compound 48/80 was added. In addition, repolarization followed by gradual depolarization was observed without degranulation in mast cells treated with cytochalasin D after the addition of compound 48/80. These results suggest that the mast cells were depolarized by compound 48/80 independently of degranulation. It is also feasible that the gradual depolarization and repolarization induced by compound 48/80 in mast cells pretreated with cytochalasin D participated in the extracellular Na+ and Na+/K(+)-pump, respectively.


Assuntos
Mastócitos/efeitos dos fármacos , Potenciais da Membrana/efeitos dos fármacos , p-Metoxi-N-metilfenetilamina/farmacologia , Animais , Citocalasina D/farmacologia , Masculino , Ratos , Ratos Wistar
13.
J Am Chem Soc ; 123(8): 1792-3, 2001 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-11456794
14.
Methods Find Exp Clin Pharmacol ; 23(7): 383-8, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11771852

RESUMO

The effects of histamine and related compounds on the differentiation of HL-60-Eo cells into eosinophils were studied. The histamine and H2 agonists impromidine and 4-methylhistamine caused concentration-related increases in the number of differentiated cells. On the other hand, the H1 agonists 2-methylhistamine and 2-pyndylethylamine showed no such effect. Histamine-induced eosinophil differentiation was antagonized by the H2 antagonists cimetidine and ranitidine. Histamine and H2 agonists inhibited (3H)-thymidine uptake, suggesting that these compounds caused a decrease in proliferation. Histamine as well as the H2 agonists impromidine and 4-methythistamine caused increases in cAMP level, and this effect was antagonized by ranitidine. From these findings, we concluded that both the differentiation of HL-60-Eo cells into eosinophils and proliferation of HL-60-Eo cells were mediated via H2 receptors.


Assuntos
Eosinófilos/efeitos dos fármacos , Células HL-60/efeitos dos fármacos , Histamina/farmacologia , Diferenciação Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Cimetidina/farmacologia , AMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Eosinófilos/citologia , Eosinófilos/metabolismo , Células HL-60/citologia , Células HL-60/metabolismo , Histamina/análogos & derivados , Agonistas dos Receptores Histamínicos/farmacologia , Antagonistas dos Receptores Histamínicos H1/farmacologia , Antagonistas dos Receptores H2 da Histamina/farmacologia , Humanos , Impromidina/farmacologia , Metilistaminas/metabolismo , Metilistaminas/farmacologia , Ranitidina/farmacologia , Receptores Histamínicos H2/metabolismo , Timidina/farmacocinética , Fatores de Tempo , Trítio
15.
Jpn J Pharmacol ; 87(3): 226-30, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11885972

RESUMO

The influence of the protein kinase A (A kinase) system in differentiation of HL-60-Eo cells to eosinophils induced by histamine was studied. Although 8-Cl-cAMP caused inhibitions of proliferation and [3H]thymidine uptake of HL-60-Eo cells similarly to histamine, no significant eosinophilic differentiation was observed. Histamine as well as 8-Cl-cAMP caused elevation of A kinase activity. However, KT-5720, an inhibitor of A kinase, had no effect on histamine-induced eosinophil differentiation. RIalpha antisense oligodeoxynucleotide caused significant inhibition of HL-60-Eo cell growth, but RIIbeta antisense oligodeoxynucleotide had no effect. On the other hand, neither of the antisense oligodeoxynucleotides showed potentiating effects on growth inhibition induced by histamine. In addition, RIalpha and RIIbeta antisense oligodeoxynucleotides caused neither differentiation to eosinophils itself nor potentiation of histamine-induced differentiation. From these findings, it was concluded that A kinase is not correlated directly with differentiation of HL-60-Eo cells to eosinophils.


Assuntos
8-Bromo Monofosfato de Adenosina Cíclica/análogos & derivados , Carbazóis , Proteínas Quinases Dependentes de AMP Cíclico/fisiologia , Eosinófilos/fisiologia , Histamina/farmacologia , 8-Bromo Monofosfato de Adenosina Cíclica/farmacologia , Diferenciação Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Células HL-60 , Humanos , Indóis/farmacologia , Oligonucleotídeos Antissenso/farmacologia , Subunidades Proteicas , Pirróis/farmacologia , Timidina/metabolismo
16.
J Allergy Clin Immunol ; 106(5): 896-903, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11080712

RESUMO

BACKGROUND: Although the existence of functional beta(2)-adrenoceptor on eosinophils has been reported, the effects of desensitization of beta(2)-adrenoceptors on eosinophils have not been well documented. OBJECTIVE: The effects of desensitization of beta(2)-adrenoceptors on the degranulation of guinea pig eosinophils were investigated. METHODS: Guinea pig eosinophils were stimulated with the calcium ionophore A23187, and eosinophil peroxidase (EPO) release was determined. Changes in intracellular cyclic adenosine monophosphate (cAMP) levels were also measured. RESULTS: A23187-induced EPO release from guinea pig eosinophils was inhibited in a concentration-dependent manner by pretreatment for 5 minutes with fenoterol, clenbuterol, and salbutamol. Such effects of beta(2)-agonists were abolished by pretreatment with KT5720, an inhibitor of protein kinase A. Desensitization of the inhibitory effects of beta(2)-agonists was observed when the incubation time was prolonged. Fenoterol (10(-6) mol/L) induced almost complete desensitization after 120 minutes of incubation, whereas clenbuterol did not bring about significant desensitization. The inhibitory effects of fenoterol and clenbuterol on A23187-induced EPO release were correlated with increases in the intracellular cAMP levels evoked by either compound. After incubation of eosinophils with 10(-6) mol/L fenoterol for 120 minutes to induce complete desensitization of beta(2)-adrenoceptors, the inhibitory effects of theophylline and rolipram were increased by about 100-fold in the desensitized cells, although the effects of forskolin and dibutyryl cAMP were not affected by beta(2)-adrenoceptor desensitization. CONCLUSIONS: Prolonged incubation with beta(2)-agonists induced desensitization of beta(2)-adrenoceptors. Also, we postulated that hypersensitization of phosphodiesterase to its inhibitors occurs in beta(2)-adrenoceptor-desensitized guinea pig eosinophils.


Assuntos
Agonistas Adrenérgicos beta/metabolismo , Carbazóis , Eosinófilos/enzimologia , Inibidores de Fosfodiesterase/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Teofilina/metabolismo , Agonistas Adrenérgicos beta/farmacologia , Albuterol/metabolismo , Albuterol/farmacologia , Animais , Bucladesina/metabolismo , Bucladesina/farmacologia , Calcimicina/farmacologia , Células Cultivadas , Clembuterol/metabolismo , Clembuterol/farmacologia , Colforsina/metabolismo , Colforsina/farmacologia , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Peroxidase de Eosinófilo , Eosinófilos/citologia , Eosinófilos/efeitos dos fármacos , Fenoterol/metabolismo , Fenoterol/farmacologia , Cobaias , Indóis/farmacologia , Líquido Intracelular/metabolismo , Ionóforos/farmacologia , Masculino , Peroxidases , Inibidores de Fosfodiesterase/farmacologia , Pirróis/farmacologia , Teofilina/farmacologia , Fatores de Tempo
17.
Jpn J Pharmacol ; 83(4): 293-9, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11001174

RESUMO

The regulatory mechanism of degranulation of guinea pig peritoneal eosinophils was studied by determination of eosinophil peroxidase (EPO) release. Beta-agonists, such as isoproterenol, salbutamol and fenoterol, effectively inhibited A23187-induced EPO release from guinea pig eosinophils. The inhibitory effects of beta-agonists were attenuated by pretreatment with either propranolol, a non-selective beta-antagonist, or ICI 118,551, a selective beta2-antagonist. Both theophylline and dibutyryl-cAMP (db-cAMP) also significantly inhibited A23187-induced EPO release. The inhibition of EPO release induced by db-cAMP was attenuated by pretreatment with KT5720, a protein kinase A inhibitor. In addition, calphostin C as well as cytochalasin D effectively inhibited A23187-induced EPO release. From the results of the present study, it was concluded that an increase in intracellular Ca2+ concentration may lead to exocytosis of eosinophil granules through activation of protein kinase C and microfilaments. Beta-agonists and theophylline were effective in inhibiting degranulation of eosinophils by increasing intracellular cAMP level coupled with the activation of protein kinase A.


Assuntos
Eosinófilos/enzimologia , Peroxidases/metabolismo , Agonistas Adrenérgicos beta/farmacologia , Animais , Calcimicina/antagonistas & inibidores , Calcimicina/farmacologia , Cálcio/metabolismo , Citocalasina D/farmacologia , Peroxidase de Eosinófilo , Eosinófilos/efeitos dos fármacos , Cobaias , Ionóforos/antagonistas & inibidores , Ionóforos/farmacologia , Masculino , Inibidores da Síntese de Ácido Nucleico/farmacologia , Peroxidases/efeitos dos fármacos
18.
Immunopharmacology ; 41(1): 55-63, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9950269

RESUMO

When rat peritoneal mast cells were exposed to ultraviolet (UV) light (UVA, UVB and UVC), histamine release was evoked in a dose (intensity X time) dependent manner. The potency order of UV light in inducing the histamine release was UVC > UVB >> UVA. In this study, we focused on the effect of ultraviolet B (UVB) on histamine release from rat mast cells. The UVB-induced histamine release occurred at doses higher than 7.8 kJ m(-2), even at 4 degrees C. At a UVB dose of 18.8 kJ m(-2), where a 51.9+/-4.8% histamine release and a 58.8+/-6.8% degranulation took place, Trypan blue-stained cells accounted for 14.4+/-1.3% of the cells, and the lactate dehydrogenase (LDH) release was about 4.9+/-2.8%. This suggests that the membrane permeability to low molecular weight substances was increased by UVB exposure. The UVB-induced histamine release was inhibited by ascorbic acid at concentrations higher than 500 microM, suggesting the involvement of a radical reaction in the process. The UVB-induced histamine release was enhanced by some phenothiazine compounds, i.e., promethazine, trimeprazine, mequitazine, chlorpromazine, trifluoperazine, ethopropazine and thioridazine. We conclude that the phototoxicity of phenothiazine compounds may be due in part to an enhancement of UVB-induced histamine release from mast cells.


Assuntos
Adjuvantes Imunológicos/farmacologia , Liberação de Histamina/efeitos dos fármacos , Liberação de Histamina/efeitos da radiação , Mastócitos/efeitos da radiação , Fenotiazinas/farmacologia , Raios Ultravioleta , Animais , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Temperatura Baixa , Masculino , Mastócitos/metabolismo , Cavidade Peritoneal/citologia , Ratos , Ratos Wistar
19.
Jpn J Pharmacol ; 75(2): 115-21, 1997 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9414025

RESUMO

Histamine at concentrations higher than 10(-9) M significantly elicited cortisol secretion from bovine adrenocortical (BAC) cells co-incubated with bovine adrenal medullary (BAM) cells, suggesting that BAM cells are responsible for histamine-induced cortisol secretion. Cortisol secretion from BAC cells co-incubated with BAM cells was also elicited by both an H1 agonist, 2-methylhistamine, and an H2 agonist, 4-methylhistamine. However, 4-methylhistamine was much less effective than 2-methylhistamine. Histamine-induced cortisol secretion was inhibited not only by H1 antagonists (pyrilamine and diphenhydramine) but also by H2 antagonists (cimetidine and ranitidine). Histamine effectively increased 45Ca uptake and IP3 production in BAM cells. These responses were antagonized by the H1 antagonist but not by the H2 antagonist. Histamine-induced cortisol secretion from BAC cells co-incubated with BAM cells was inhibited by beta-adrenoceptor antagonists, propranolol and timolol, as well as an NK1-receptor antagonist, D-Arg1-D-Trp7,9-Leu11-substance P. These results indicate that histamine can induce cortisol secretion from BAC cells at physiological concentrations through H1 receptors on BAM cells, and catecholamine and substance P may participate in histamine-induced cortisol secretion.


Assuntos
Córtex Suprarrenal/efeitos dos fármacos , Medula Suprarrenal/efeitos dos fármacos , Histamina/farmacologia , Hidrocortisona/metabolismo , Córtex Suprarrenal/metabolismo , Medula Suprarrenal/fisiologia , Animais , Cálcio/metabolismo , Bovinos , Células Cultivadas , Técnicas de Cocultura , Antagonistas dos Receptores Histamínicos , Inositol 1,4,5-Trifosfato/biossíntese
20.
Arzneimittelforschung ; 47(4): 390-4, 1997 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9150859

RESUMO

WP-871 (3'-(1H-tetrazol-5-yl)oxanilic acid monohydrate, CAS 114607-46-4) is a monohydrate of a main active metabolite of tazanolast (butyl 3'-(1H-tetrazol-5-yl) oxanilate, CAS 82989-25-1), an orally active antiallergic drug. WP-871 inhibited dose-dependently compound 48/80-induced histamine release from rat peritoneal mast cells. In a similar dose range, WP-871 was effective in inhibiting compound 48/80-induced 45Ca uptake into mast cells from extracellular medium and compound 48/80-induced translocation of protein kinase C from the cytosol to the membrane fraction of mast cells. WP-871 also inhibited inositol trisphosphate production but did not exhibit a direct inhibitory effect on phospholipase C in mast cells. WP-871 caused no increase in cAMP content in mast cells. These results suggest that WP-871 may inhibit histamine release mainly by preventing the increase in intracellular Ca2+ concentration, which is a critical event in signal transduction leading to histamine release in mast cells.


Assuntos
Antialérgicos/farmacologia , Liberação de Histamina/efeitos dos fármacos , Mastócitos/metabolismo , Tetrazóis/farmacologia , Animais , Radioisótopos de Cálcio , AMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Técnicas In Vitro , Inosina Trifosfato/metabolismo , Masculino , Mastócitos/efeitos dos fármacos , Oxalatos , Proteína Quinase C/metabolismo , Ratos , Ratos Wistar , Fosfolipases Tipo C/metabolismo
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