RESUMEN
In STA-MCA bypass surgery, it is important to select the optimal recipient using preoperative simulation to avoid complications. We report a preoperative simulation for STA-MCA bypass using the Brain LAB iPLAN platform®BRAIN LAB)and the 3DCG simulation software GRID®Kompath). Here, we introduce the basics and applications of preoperative simulation for occlusive atherosclerotic lesions and present a target bypass for periventricular anastomosis and peripheral vessels of aneurysms in Moyamoya disease. By creating and visualizing 3D fusion images, the optimal donor and recipient can be selected. Determining the skin incision and extent of craniotomy according to the case is also applicable to the minimally invasive STA-MCA bypass. Preoperative simulations enable accurate pinpoint bypass surgery and prevent complications.
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Revascularización Cerebral , Enfermedad de Moyamoya , Humanos , Revascularización Cerebral/métodos , Arteria Cerebral Media/cirugía , Arterias Temporales , Enfermedad de Moyamoya/diagnóstico por imagen , Enfermedad de Moyamoya/cirugía , Enfermedad de Moyamoya/complicaciones , EncéfaloRESUMEN
A 62-year-old woman was diagnosed as a hemophilia A carrier (factor VIII activity 35%) on preoperative examination of an ovarian tumor. A total of 35,600 units of recombinant factor VIII products was administered perioperatively. On postoperative day 95, a subcutaneous hematoma formed and immunosuppressive therapy with prednisolone was started based on an APTT of 66 seconds, factor VIII (FVIII) activity of 3%, and FVIII inhibitor of 1 BU/ml. During this treatment, the patient was hospitalized due to ankle joint bleeds and required hemostatic treatment, but the inhibitor disappeared and FVIII activity recovered to 30% after postoperative day 438 with cyclophosphamide. F8 analysis revealed the patient carried a heterozygosity of p.Arg391Cys, which has previously been categorized as cross-reacting material (CRM)-positive severe hemophilia A. No high-risk mutations for inhibitor development were found. We also report the results of a desmopressin acetate hydrate test administered to the patient to prepare for future treatment in case of hemorrhage, since high-dose FVIII administration may have been a factor in inhibitor development.
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Hemofilia A , Hemostáticos , Femenino , Humanos , Persona de Mediana Edad , Factor VIII/uso terapéutico , Hemofilia A/tratamiento farmacológico , Hemostáticos/uso terapéutico , Hemartrosis , Terapia de InmunosupresiónRESUMEN
AIM: Many women with inherited bleeding disorders are not diagnosed because of a lack of appropriate indicators. This study aimed to assess the predictability of the pictorial blood loss assessment chart (PBAC) as an indicator of menorrhagia and identify an easy indicator of menorrhagia resulting from bleeding disorders. METHODS: A multicenter study enrolled 9 patients with von Willebrand disease (VWD), 23 hemophilia carriers, and 71 controls aged 20-45 years who completed PBACs for two menstrual cycles as well as questionnaires. RESULTS: The PBAC scores of the VWD were significantly higher than those of other groups, even in multivariate analysis with age and sanitary item factors (p = 0.014). A PBAC score of 100 was not an appropriate cutoff because of its low specificity (VWD: sensitivity, 100; specificity, 29.5; hemophilia carriers: 74 and 29.5, respectively). In the ROC analysis, the cutoff of optimal PBAC for VWD was 171 (sensitivity, 66.7; specificity, 72.3; AUC, 0.7296). As the pad length increased, the total length of the pads used during one menstrual period could be a new and easy indicator. However, the cutoff for VWD was 735 cm (sensitivity, 42.9; specificity, 94.3; AUC 0.6837). A threshold could not be established for the hemophilia carrier. Therefore, we multiplied the coefficient by the length of thick pads, which caused a lower PBAC. For the VWD, the sensitivity increased to 85.7 (specificity, 77.1). For the hemophilia carrier, sensitivity (66.7) and specificity (88.6) could be separated from the control. CONCLUSIONS: The total length of the pads with a thick-pad adjustment can be a simple method to identify bleeding disorders.
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Hemofilia A , Menorragia , Enfermedades de von Willebrand , Femenino , Humanos , Hemofilia A/complicaciones , Hemorragia , Menorragia/diagnóstico , Menorragia/etiología , Encuestas y Cuestionarios , Enfermedades de von Willebrand/complicaciones , Adulto , Persona de Mediana EdadRESUMEN
BACKGROUND: Inhibitor-development is a serious complication in patients with haemophilia (PwH). Previous studies reported that therapeutic and genetic factors could be associated with these alloantibodies. Relevant clinical features such as genetic-background and different treatment regimens in Japan remain unclear, however. AIMS: To analyse a nation-wide Japanese registry for PwH, and to examine risk factors for inhibitor-development. METHODS AND RESULTS: Newly diagnosed patients with haemophilia A (PwHA) or haemophilia B (PwHB) without inhibitors after 2007, and with treatment records traceable from 0 to 75 exposure days (ED), were enrolled in the Japan Hemophilia Inhibitor Study 2 (J-HIS2) initiated in 2008. Of 417 patients (340 PwHA, 77 PwHB) from 46 facilities, 83 (76 PwHA, 7 PwHB) were recorded with inhibitors by July 2020. Inhibitors were observed in 31.0% of severe PwHA, 8.0% moderate and 1.6% mild and in 17.1% of severe PwHB. The majority of inhibitors (89.7% in severe PwHA and 71.4% in severe PwHB) were detected on or before 25ED (median 12ED in PwHA and 19ED in PwHB). Genotyping in these severe patients identified an association between inhibitor-development and null variants of F8 (P < .01) or F9 (P < .05). A lower incidence of inhibitors was recorded in severe PwHA treated with prophylaxis than in those treated on-demand (P < .01). A past-history of intracranial-haemorrhage appeared to be associated with inhibitor-development, while FVIII-concentrates infusion and routine vaccination on the same day was not related to inhibitor-development. CONCLUSION: The J-HIS2 study has identified significant clinical variables associated with inhibitor-development in Japanese PwH, consistent with other global studies.
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Hemofilia A , Factor VIII/genética , Factor VIII/uso terapéutico , Hemofilia A/complicaciones , Hemofilia A/tratamiento farmacológico , Hemofilia A/genética , Humanos , Japón/epidemiología , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Eosinophilic enteritis is a chronic inflammatory disorder of the intestinal tract that is characterized by eosinophil infiltration. Cytomegalovirus (CMV), a common virus, has a broad infectivity range. CMV is retained in the host body after infection. Impairment of host immune defences may reactivate the latent CMV, leading to symptoms of overt disease. CASE PRESENTATION: A Japanese female in her 70 s was admitted to a hospital due to diarrhoea and then transferred to our hospital. Laboratory data showed hypoalbuminemia. Computed tomography (CT) revealed oedema of the small intestine. Lower gastrointestinal endoscopy revealed oedema of the submucosa, without any remarkable changes in the mucosa of the terminal ileum. Histological examination of the terminal ileum revealed infiltration of > 20 eosinophils per high-power field (HPF). These findings aided in diagnosing eosinophilic enteritis. We administered methylprednisolone (500 mg/day) for three days, followed by tapering prednisolone. However, the patient's general condition and hypoalbuminemia failed to improve. Immunoglobulin (Ig) G- CMV and IgM-CMV tests were positive. CMV antigenemia was extremely high. Therefore, we administered ganciclovir intravenously, which improved the patient's condition. Furthermore, azathioprine was administered to taper and discontinue prednisolone without relapse of eosinophilic enteritis. This treatment helped stabilize the patient's condition for approximately four years. CONCLUSION: We present a case of eosinophilic enteritis accompanied by CMV disease during prednisolone treatment. The patient's condition improved after administration of ganciclovir. Azathioprine aided in discontinuing prednisolone and stabilizing the patient's condition for approximately four years.
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Infecciones por Citomegalovirus , Hipoalbuminemia , Azatioprina/uso terapéutico , Citomegalovirus , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/tratamiento farmacológico , Enteritis , Eosinofilia , Femenino , Ganciclovir/uso terapéutico , Gastritis , Humanos , Hipoalbuminemia/tratamiento farmacológico , Hipoalbuminemia/etiología , Prednisolona/uso terapéuticoRESUMEN
We report a case of bone marrowmetastases of breast cancer treated with endocrine therapy. A 54-year-old woman underwent right partial mastectomy and sentinel lymph node biopsy, followed by adjuvant chemotherapy and radiotherapy. She declined the endocrine therapy and was lost to follow-up after 3 postoperative years. After 9 postoperative years, she visited our hospital because of backache and an axillary lump. FDG-PET scan, incisional biopsy of the axillary lump, and bone marrowbiopsy revealed multiple bone and bone marrowmetastases of the breast cancer. She was treated with endocrine therapy(fulvestrant: FUL), which effectively decreased the FDG uptake in the metastatic lesions after 6 months. However, tumor markers elevated after 1 year and 6 months, and she is currently under combination therapy with aromatase inhibitors and CDK4/6 inhibitors.
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Neoplasias de la Médula Ósea , Neoplasias de la Mama , Neoplasias de la Médula Ósea/secundario , Neoplasias de la Médula Ósea/terapia , Neoplasias de la Mama/terapia , Femenino , Humanos , Mastectomía , Mastectomía Segmentaria , Persona de Mediana Edad , Biopsia del Ganglio Linfático CentinelaRESUMEN
Kidney transplant recipients (KTRs) taking immunosuppressive drugs have a 20-fold greater risk of nontyphoidal Salmonella (NTS) infection than the healthy adult population. Among KTRs, the urinary tract is the most common site of infection. However, few cases of urinary tract infection caused by NTS have been documented in KTRs, and only one in Japan. Furthermore, it frequently induces acute allograft rejection with high mortality. Salmonella enterica subsp. enterica serovar Schwarzengrund (S. Schwarzengrund) is now among the more common Salmonella serovars isolated in Japan and is likely to be invasive. We present a case of a 45-year old female with vesicoureteral reflux to her transplanted kidney who developed kidney allograft pyelonephritis caused by S. Schwarzengrund. She was admitted to our hospital with fever, urodynia, lower abdominal pain, gross hematuria, and cloudy urine. Urine cultures were positive for S. Schwarzengrund. Exposure to cats, especially stray cats, were identified as the most likely source. We administered antibiotics for 4 weeks (ceftriaxone then amoxicillin, each for 2 weeks) and educated her about pet safety. She experienced no recurrence of infection or clinical kidney allograft rejection for 3 months post-treatment. NTS should be considered as a possible pathogen of urinary tract infection among KTRs, especially in cases with animal exposure or structural urologic abnormalities. When the pathogen is NTS, appropriate antibiotics and treatment periods are essential for preventing recurrence and allograft rejection after the completion of treatment.
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Trasplante de Riñón/efectos adversos , Pielonefritis , Infecciones por Salmonella , Salmonella enterica , Aloinjertos , Animales , Antibacterianos/uso terapéutico , Gatos , Femenino , Humanos , Huésped Inmunocomprometido , Persona de Mediana Edad , Pielonefritis/diagnóstico , Pielonefritis/tratamiento farmacológico , Pielonefritis/microbiología , Infecciones por Salmonella/diagnóstico , Infecciones por Salmonella/tratamiento farmacológico , Infecciones por Salmonella/microbiología , Infecciones Urinarias , Reflujo VesicoureteralRESUMEN
The patient was a 53-year-old woman with a large left breast tumor. Triple-negative breast cancer with bilateral axillary lymph-node metastasis and bone metastasis was diagnosed. The primary treatment consisted of chemotherapy with a combination of paclitaxel(PTX 80mg/m 2)and bevacizumab(Bev 10 mg/kg). After chemotherapy, the tumor shrunk and showed an obvious decrease in size, eventually disappearing. After therapy, an ulcer was detected on the left breast, and mastectomy and axillary lymph node dissection were performed. The patient's postoperative course was uneventful and she has been receiving chemotherapy at our outpatient clinic. Thus, combination therapy with PTX and Bev may be useful for the local control of advanced breast cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Bevacizumab , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/secundario , Terapia Combinada , Femenino , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática , Mastectomía , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/cirugíaRESUMEN
OBJECTIVE: This prospective study used the EQ-5D utility and Visual Analogue Scale (VAS) scores to analyse the potential usefulness of proxy responses in quality of life assessments of Japanese patients with terminal lung cancer sufficiently healthy to communicate and reply by themselves. We did not investigate the potential usefulness of using proxy responses for patients who could not respond by themselves. DESIGN: A prospective observational study. SETTING: Single centre. PARTICIPANTS: The EQ-5D and VAS responses were gathered from 30 in-hospital patients with lung cancer for a total of three observation points. At nearly the same time, two nurses responded by providing proxy responses. PRIMARY AND SECONDARY OUTCOME MEASURES: EQ-5D and VAS responses. RESULTS: There were no significant differences between the patients' and nurses' responses for EQ-5D utility and VAS scores. For the five dimensions of the EQ-5D, significant differences were found between the patients' and nurses' responses for usual activities (patients' response 1.64±0.07, nurses' response 1.41±0.05, p=0.03) and anxiety/depression (patients' response: 1.40±0.05, nurses' response: 1.19±0.03, p=0.02). There was a significant weak positive correlation between patients' and nurses' responses regarding changes in responses from the first to the third observation point (Spearman's rank correlation coefficient ρ=0.228; p<0.01). CONCLUSION: The results suggest that proxy responses are useful because there were no significant differences between the patients' and nurses' responses for EQ-5D utility and VAS scores at the three observation points. These findings should, however, be verified in future large-scale trials.
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Neoplasias Pulmonares , Calidad de Vida , Humanos , Estudios Prospectivos , Apoderado , Encuestas y CuestionariosRESUMEN
A 10-day-old male patient was referred to our hospital with severe umbilical bleeding. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were prominently prolonged. Plasma coagulation factor X (FX) activity and antigen levels were 1% and 0.6%, respectively. A DNA sequence analysis of his leukocytes revealed a compound heterozygous state; known Gly244 to Arg (p.G244R) in exon 6 and a novel mutation of Gly 435 to Ser (p.G435S) in exon 8. A pedigree analysis showed that p.G244R originated from the paternal side, while p.G435S was from the maternal side. A p.G244R mutation was reported previously as FXDebrecen and this mutated protein was synthesized as a non-secretable protein. The glycine at amino acid position 435 in the C-terminal region is completely conserved in the trypsin-like serine protease family, including thrombin, FVII, protein C, plasmin, trypsin, and chymotrypsin. In a three-dimensional structural model of FX, Gly 435 was located within the 11th ß-strand and buried in the back of the catalytic pocket. Therefore, the substitution to serine was expected to disrupt this structure. p.G435S FX was also predicted to be synthesized and exist in the cytoplasm, but not to be secreted into culture media by a cDNA expression assay. These two mutations may be responsible for the type 1 (null levels of both activity and antigen in plasma) FX deficiency with severe bleeding phenotype.
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Deficiencia del Factor X/complicaciones , Deficiencia del Factor X/genética , Factor X/genética , Hemorragia/complicaciones , Hemorragia/genética , Ombligo/patología , Aminoácidos , Pruebas de Coagulación Sanguínea , Exones , Femenino , Heterocigoto , Humanos , Recién Nacido , Masculino , Mutación , Padres , Tiempo de Tromboplastina Parcial , Linaje , Fenotipo , Conformación Proteica , Tiempo de Protrombina , Tripsina/químicaRESUMEN
Cyst infection is one of the major complications in patients with autosomal dominant polycystic kidney disease (ADPKD). The causative pathogen in kidney cyst infection frequently goes undetected. Although only one case report of kidney cyst infection caused by Helicobacter cinaedi (H. cinaedi) is published in English literature, it may be an important pathogen in kidney cyst infection. Kidney cyst infection and H. cinaedi infection share the common characteristic of tendency to relapse and chronic kidney disease is a major risk factor for H. cinaedi infection. Moreover, a long period is required to detect H. cinaedi in blood cultures, potentially causing false-negative results. After the identification of H. cinaedi, we must carefully select antibiotics and the antibiotic treatment period should be extended to prevent recurrence. Here we present a case of a 58-year-old male with ADPKD who developed bacteremic kidney cyst infection caused by H. cinaedi. He was admitted to our hospital because of fever, lower left back pain, vomiting, and feeling of abdominal enlargement. H. cinaedi was detected from the blood cultures obtained at admission after 4 days of culture. Antibiotics were administered for 8 weeks after confirming negative blood cultures. There was no evidence of kidney cyst infection relapse at 3 months after treatment completion. Nephrologists should regard H. cinaedi as a challenging but important pathogen in kidney cyst infection, particularly when the causative organism is unknown or kidney cyst infection is recurrent.
RESUMEN
BACKGROUND: Magnetic resonance imaging (MRI) is useful in pathogenesis, diagnosis, and treatment. CASE: A 70-year-old man. He noticed that the right side of his upper lid had swollen 3 weeks previously. No abnormal findings were recognized in visual acuity, intraocular pressure, anterior segment, lens, vitreous, or fundus. From MRI findings 10 days after his first visit, dermoid cyst, soft tissue tumor, and nodular fasciitis were suspected. Because MRI 2 months after the first visit showed a decrease in tumor size, soft tissue tumor was ruled out. Finally histopathological examination revealed nodular fasciitis, although the findings during the operation did not differentiate between dermoid cyst and nodular fasciitis. CONCLUSION: MRI at different intervals was useful for clinical diagnosis.
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Párpados/patología , Fascitis/diagnóstico , Fascitis/patología , Imagen por Resonancia Magnética , Anciano , Diagnóstico Diferencial , Párpados/cirugía , Fascitis/cirugía , Humanos , Masculino , Monitoreo Fisiológico , Factores de TiempoRESUMEN
PURPOSE: To determine whether FR118487, a recently developed angiogenesis inhibitor, affects experimental choroidal neovascularization (CNV) induced by laser photocoagulation in pigmented rats. METHODS: Focal laser photocoagulation (argon green 50 mW, 0.04 seconds, 200 microm) was applied to the retinochoroid of normal Brown Norway rats. Systemic administration of FR118487 (1.0 mg/kg body weight per day) with a mini-osmotic pump implanted in the subcutaneous tissue of the neck was started just after laser photocoagulation and continued for 2 weeks. Choroidal vascular casts were made 2 weeks after laser photocoagulation and were examined with a scanning electron microscope. CNV formation was divided into three grades and evaluated. RESULTS: Laser-induced CNV formation was significantly less in rats given FR118487 than in control rats. CNVs in rats treated with FR118487 were less well developed than in the controls. CONCLUSION: FR118487 inhibits the development of experimental CNV induced by photocoagulation in pigmented rats.
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Inhibidores de la Angiogénesis/farmacología , Neovascularización Coroidal/prevención & control , Endotelio Vascular/efectos de los fármacos , Compuestos de Espiro/farmacología , Animales , Capilares/ultraestructura , Neovascularización Coroidal/etiología , Molde por Corrosión , Esquema de Medicación , Endotelio Vascular/crecimiento & desarrollo , Coagulación con Láser , Microscopía Electrónica de Rastreo , Ratas , Ratas Endogámicas BN , Compuestos de Espiro/administración & dosificaciónRESUMEN
A 65-year-old Japanese male developed renal dysfunction, showing proteinuria and marked urinary excretion of beta2-microglobulin. He had consumed approximately 100-200 g peanuts and 750-1,000 ml beer every day for two or three months. He had previously been treated for hypertension with an angiotensin-converting enzyme inhibitor, enalapril. He then visited his primary-care doctor with mild fever, and renal dysfunction with mild diabetes mellitus were diagnosed. He was referred to our hospital, and because no diabetic retinopathy was observed by ophthalmological tests, renal biopsy examination was performed to clarify renal dysfunction. Renal biopsy specimens showed intimal thickening in the small arteries and interstitial nephritis with a granulomatous lesion, accompanied by oxalate crystals under polarized light. Glomeruli were unremarkable without any immunoglobulin deposition, and nodular lesions. Because he daily consumed a large amount of peanuts, oxalate nephropathy due to excessive intake of peanuts was strongly suspected. This case revealed that unusual food habits, including nuts, can cause oxalate nephropathy, and that close examination by renal biopsy was useful for clarifying the etiology of the unknown renal damage.
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Arachis/efectos adversos , Riñón/metabolismo , Nefritis Intersticial/diagnóstico , Nefritis Intersticial/metabolismo , Oxalatos/metabolismo , Anciano , Biopsia , Humanos , Riñón/fisiopatología , Masculino , Proteinuria/fisiopatología , Microglobulina beta-2/orinaRESUMEN
Parasporin-2, a new crystal protein derived from noninsecticidal and nonhemolytic Bacillus thuringiensis, recognizes and kills human liver and colon cancer cells as well as some classes of human cultured cells. Here we report that a potent proteinase K-resistant parasporin-2 toxin shows specific binding to and a variety of cytocidal effects against human hepatocyte cancer cells. Cleavage of the N-terminal region of parasporin-2 was essential for the toxin activity, whereas C-terminal digestion was required for rapid cell injury. Protease-activated parasporin-2 induced remarkable morphological alterations, cell blebbing, cytoskeletal alterations, and mitochondrial and endoplasmic reticulum fragmentation. The plasma membrane permeability was increased immediately after the toxin treatment and most of the cytoplasmic proteins leaked from the cells, whereas mitochondrial and endoplasmic reticulum proteins remained in the intoxicated cells. Parasporin-2 selectively bound to cancer cells in slices of liver tumor tissues and susceptible human cultured cells and became localized in the plasma membrane until the cells were damaged. Thus, parasporin-2 acts as a cytolysin that permeabilizes the plasma membrane with target cell specificity and subsequently induces cell decay.
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Antineoplásicos/farmacología , Bacillus thuringiensis/química , Toxinas Bacterianas/farmacología , Endotoxinas/metabolismo , Endotoxinas/farmacología , Neoplasias Hepáticas/metabolismo , Hígado/efectos de los fármacos , Animales , Antineoplásicos/metabolismo , Toxinas Bacterianas/genética , Toxinas Bacterianas/metabolismo , Membrana Celular/efectos de los fármacos , Forma de la Célula , Células Cultivadas , Citoesqueleto/efectos de los fármacos , Citoesqueleto/metabolismo , Endopeptidasa K/metabolismo , Endotoxinas/genética , Humanos , Hígado/citología , Hígado/metabolismo , Hígado/patología , Neoplasias Hepáticas/patología , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMEN
PURPOSE: To determine whether irsogladine inhibits experimental choroidal neovascularization (CNV) induced by laser photocoagulation in pigmented rats. METHODS: Focal laser photocoagulation (argon green 50 mW, 0.04 s, 200 microm) was applied to the retinochoroid of normal Brown Norway rats. Oral administration of irsogladine (5 mg/kg/day or 50 mg/kg/day) was started 1 week before and continued for 2 weeks after laser photocoagulation. Choroidal vascular casts were made 2 weeks after laser photocoagulation and were examined with a scanning electron microscope (SEM). CNV formation was classified according to three grades and evaluated. RESULTS: Laser-induced CNV formation was significantly reduced in rats given 5 mg/kg/day (p < 0.01) or 50 mg/kg/day of irsogladine (p < 0.001). Administration of 50 mg/kg/day of irsogladine was more effective in preventing CNV formation than 5 mg/kg/day (p < 0.001). The development of the vascular bud was especially inhibited by 50 mg/kg/day of irsogladine (p < 0.001). CNVs in rats treated with 50 mg/kg/day of irsogladine looked less well developed than those in controls. There was no significant side effect of irsogladine. CONCLUSIONS: Irsogladine inhibits the development of experimental CNV induced by photocoagulation in pigmented rats.
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Antiulcerosos/uso terapéutico , Neovascularización Coroidal/tratamiento farmacológico , Triazinas/uso terapéutico , Animales , Capilares/efectos de los fármacos , Capilares/ultraestructura , Coroides/efectos de los fármacos , Coroides/ultraestructura , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación/veterinaria , Evaluación Preclínica de Medicamentos , Coagulación con Láser/métodos , Microscopía Electrónica de Rastreo/instrumentación , Microscopía Electrónica de Rastreo/métodos , Ratas , Ratas Endogámicas BN , Factores de TiempoRESUMEN
ACE inhibitors are known to ameliorate cardiovascular complications in aging; however, their effects on the coronary circulation in relation to aging and eNOS dependence remain to be examined. Coronary flow responses to bradykinin with or without ACE inhibitors were examined in Langendorff-perfused hearts from young (16-20 weeks) and aged (16-20 months) control and eNOS mice. Western blot analysis was performed for cardiac eNOS, nNOS, and ACE. Baseline coronary flow was comparable between young and aged mice of both strains. Aging did not affect bradykinin-induced coronary flow in either strain. Interestingly, both acute and chronic treatment with an ACE inhibitor markedly augmented the flow response in aged control and eNOS mice. Aged eNOS mice were markedly hypertensive and had larger ventricular mass than control mice. The antihypertensive effect of temocapril was greater in aged eNOS mice, associated with reduction in the ventricular weight in both strains. Western blot analysis demonstrated an increased expression of eNOS in aged control mice, and ACE expression was increased in eNOS mice. These results indicate that coronary flow response to bradykinin is preserved in aged mice even in the absence of eNOS, and an ACE inhibitor augments this response by both eNOS-dependent and -independent mechanisms.