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Oral ferric citrate hydrate (FCH) is effective for iron deficiencies in hemodialysis patients; however, how iron balance in the body affects iron absorption in the intestinal tract remains unclear. This prospective observational study (Riona-Oral Iron Absorption Trial, R-OIAT, UMIN 000031406) was conducted at 42 hemodialysis centers in Japan, wherein 268 hemodialysis patients without inflammation were enrolled and treated with a fixed amount of FCH for 6 months. We assessed the predictive value of hepcidin-25 for iron absorption and iron shift between ferritin (FTN) and red blood cells (RBCs) following FCH therapy. Serum iron changes at 2 h (ΔFe2h) after FCH ingestion were evaluated as iron absorption. The primary outcome was the quantitative delineation of iron variables with respect to ΔFe2h, and the secondary outcome was the description of the predictors of the body's iron balance. Generalized estimating equations (GEEs) were used to identify the determinants of iron absorption during each phase of FCH treatment. ΔFe2h increased when hepcidin-25 and TSAT decreased (-0.459, -0.643 to -0.276, p = 0.000; -0.648, -1.099 to -0.197, p = 0.005, respectively) in GEEs. FTN increased when RBCs decreased (-1.392, -1.749 to -1.035, p = 0.000) and hepcidin-25 increased (0.297, 0.239 to 0.355, p = 0.000). Limiting erythropoiesis to maintain hemoglobin levels induces RBC reduction in hemodialysis patients, resulting in increased hepcidin-25 and FTN levels. Hepcidin-25 production may prompt an iron shift from RBC iron to FTN iron, inhibiting iron absorption even with continued FCH intake.
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Compuestos Férricos , Hepcidinas , Humanos , Compuestos Férricos/farmacología , Ferritinas , Hierro , Estudios Prospectivos , Diálisis RenalRESUMEN
Purpose: We assessed the effect of rebamipide ophthalmic solution on corneal epithelial injury due to benzalkonium chloride (BAK) by fluorescein (FL) staining and corneal resistance (CR). Methods: After determining the absence of corneal epithelial damage by FL and CR, rebamipide ophthalmic solution (50 µL) was instilled five times, each interspaced by 5 min, into one eye of mature New Zealand white rabbits, and likewise physiological saline was instilled into the contralateral eye as the control. After 30 min, eyes were similarly treated with one of the following solutions: BAK solution 0.02%, latanoprost ophthalmic solution (0.02% BAK), or latanoprost ophthalmic solution without BAK. The presence of corneal epithelial damage was quantitated at 10, 30, and 60 min by CR after the last instillation. FL staining was also performed at 60 min after the last instillation. Results: CR ratios (%) at 60 min after the last instillation in rebamipide/BAK and rebamipide/latanoprost (0.02% BAK) groups were significantly increased by 18.3% and 25.6% compared with saline/BAK and saline/latanoprost (0.02% BAK) groups, respectively (P < 0.05). Findings by FL staining were consistent with those by CR; BAK and latanoprost with BAK groups were positive, and eyes with the most severe area and density of corneal epithelial damage (A2D2) were in the saline/BAK group. Conclusion: The rebamipide ophthalmic solution reduces the severity of corneal epithelial injury caused by BAK, an ophthalmic solution preservative.
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Alanina/análogos & derivados , Antioxidantes/farmacología , Compuestos de Benzalconio/farmacología , Epitelio Corneal/efectos de los fármacos , Epitelio Corneal/lesiones , Conservadores Farmacéuticos/farmacología , Quinolonas/farmacología , Alanina/farmacología , Animales , Quimioterapia Combinada , Latanoprost/farmacología , Masculino , Conejos , Distribución AleatoriaRESUMEN
Purpose: We sought to evaluate the effect of antiglaucoma ophthalmic solutions on the cornea with a corneal resistance device (CRD), and to compare the results with those by fluorescein staining. Methods: In 6 rabbit groups (n = 7 each), right eyes were administered latanoprost ophthalmic solution containing 0.02% benzalkonium chloride (BAK); dorzolamide/timolol (1%/0.5%) containing 0.005% BAK; dorzolamide/timolol without BAK; dorzolamide/timolol+latanoprost with 0.02% BAK; 0.005% BAK; or 0.02% BAK to the conjunctival sac 3 × at 15-min intervals. Left (control) eyes were administered saline. Baseline and post-treatment corneal resistance (CR) were measured. The CR ratio = CR before versus after treatment. We evaluated superficial punctate keratitis by fluorescein staining using area and density (AD) grades. Results: In the dorzolamide/timolol-without BAK group, there were no significant difference in the CR ratio between the control and treatment eyes at any time point. In the 0.005%-BAK group at 30 min and the other 4 groups at all time points, the CR ratio differed significantly between the control and treatment eyes (P < 0.05). AD grades were 0 in all control eyes and the dorzolamide/timolol-without BAK and 0.005% BAK treatment eyes. Conclusions: Nonpreservative ophthalmic solutions (and those with low BAK concentrations) do not significantly affect corneal electrical resistance. Eye drop ingredients other than BAK may be involved in altering corneal electrical resistance. CRDs may detect corneal epithelium changes not revealed by fluorescein staining.
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Antihipertensivos/uso terapéutico , Córnea/efectos de los fármacos , Impedancia Eléctrica , Soluciones Oftálmicas/uso terapéutico , Animales , Glaucoma/tratamiento farmacológico , Masculino , ConejosRESUMEN
Periocular povidone-iodine (PI) and polyvinyl alcohol-iodine (PAI) have had a major role in the prevention of endophthalmitis. The purpose of this study was to investigate the corneal epithelial toxicity of PAI in a rabbit eye model using corneal resistance (CR) measurement, which is a good indicator of cell barrier function. Rabbit eyes were administered PAI solution at 4-, 6-, 8-, or 16-fold dilution with physiological saline solution (saline) or saline alone (control), to the conjunctival sac with/without wash-out with saline. Corneal epithelial injury assessed by fluorescein staining and the CR ratio was measured at 10 minutes (min) to 96 hours (h) after the initial administration. Histological observation was performed in the eyes following the PAI or control administrations. At 120 min after administration of PAI solution, the CR ratio was decreased and superficial punctate keratopathy (SPK) was significantly increased in each of the PAI-administered groups compared to the control. Recovery of CR and SPK after administration of 6- or 8-fold dilution of PAI was significantly delayed in eyes that were not subsequently washed with saline compared with eyes that were. Pre- or post-instillation of 2% rebamipide ophthalmic suspension significantly reduced PAI induced-SPK and -decrease of CR ratio. The CR method was able to accurately and quantitatively evaluate fine corneal epithelial injury. It is suggested that eyes should be washed with saline solution after administration of PAI solution or the instillation of rebamipide to prevent or reduce corneal epithelial injury.
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Alanina/análogos & derivados , Lesiones de la Cornea/inducido químicamente , Lesiones de la Cornea/tratamiento farmacológico , Epitelio Corneal/efectos de los fármacos , Epitelio Corneal/lesiones , Yodo/efectos adversos , Alcohol Polivinílico/efectos adversos , Sustancias Protectoras/uso terapéutico , Quinolonas/uso terapéutico , Administración Oftálmica , Alanina/administración & dosificación , Alanina/uso terapéutico , Animales , Antioxidantes/administración & dosificación , Antioxidantes/uso terapéutico , Lesiones de la Cornea/patología , Lesiones de la Cornea/prevención & control , Epitelio Corneal/patología , Masculino , Sustancias Protectoras/administración & dosificación , Quinolonas/administración & dosificación , ConejosRESUMEN
We treated a case of acute kidney injury and nephrotic syndrome after malathion inhalation. A 69-year-old Japanese man presented with oedema 15 days after inhalation of malathion, a widely used pesticide. Serum albumin was 2.4 g/dL, urinary protein 8.6 g/gCr and serum creatinine 2.5 mg/dL. Kidney biopsy revealed tubular cell damage, epithelial cell damage in glomeruli and diffuse foot process effacement in electron microscopy. Acute kidney injury progressed to treatment with dialysis. Renal function recovered after corticosteroid administration from the 43rd day after admission. Malathion inhalation should be ruled out as a differential diagnosis in individuals who develop acute kidney injury and nephrotic syndrome, especially in rural-dwelling patients.
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Lesión Renal Aguda/diagnóstico , Malatión/toxicidad , Síndrome Nefrótico/diagnóstico , Plaguicidas/toxicidad , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/complicaciones , Lesión Renal Aguda/terapia , Anciano , Diagnóstico Diferencial , Humanos , Masculino , Síndrome Nefrótico/inducido químicamente , Síndrome Nefrótico/complicaciones , Síndrome Nefrótico/terapia , Diálisis RenalRESUMEN
PURPOSE: To examine the validity of in vivo electrical corneal resistance (CR) measurements taken by a corneal resistance device (CRD). METHODS: Eighty-two eyes (mean age ± SD, 50.1 ± 23.3; range, 22-87 years: 50 eyes of 33 males and 32 eyes of 17 females) of patients who had undergone cataract surgery and volunteers at the Kanazawa Medical University Hospital were enrolled. The CR was compared among gender; age; side, that is, left versus right eye; healthy (fluorescein-negative) versus epithelium-injured eyes (fluorescein-positive), corneal radius of curvature; corneal endothelial cell count; and corneal thickness. RESULTS: The mean ± SD of the CR in the 82 eyes was 273.2 ± 78.2 Ω. By age group, the mean ± SD CR was 283.3 ± 87.4 Ω (30 eyes) in the 20s, 275.0 ± 50.0 Ω (4 eyes) in the 30s, 266.7 ± 70.7 Ω (9 eyes) in the 40s, 257.1 ± 53.5 Ω (7 eyes) in the 50s, 242.9 ± 78.7 Ω (7 eyes) in the 60s, 266.7 ± 84.0 Ω (18 eyes) in the 70s, and 300.0 ± 81.6 Ω (7 eyes) in the 80s, with no significant difference among the groups. By gender, the mean ± SD CR was 270.0 ± 83.0 Ω (50 eyes) in males and 278.0 ± 71.0 Ω (32 eyes) in females. By side, the CR values were 282.9 ± 83.4 Ω (44 eyes) in the right eye, 265.9 ± 71.3 Ω (41 eyes) in the left eye, with no significant difference among the groups. By status, the values were 280.0 ± 70.0 Ω (44 eyes) in healthy eyes and 200.0 ± 144.2 Ω (13 eyes) in injured eyes, with a significant between-group difference (P = 0.009). The mean ± SD corneal thickness (0.56 ± 0.03 mm) in 46 healthy eyes was slightly correlated with the CR. CONCLUSIONS: The CRD quantitatively measured the CR in healthy eyes. The CR did not differ significantly by age, gender, or left versus right eye. The significant difference in CR between the healthy and injured eyes showed that the measurements have validity.
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Córnea/fisiología , Impedancia Eléctrica , Adulto , Anciano , Anciano de 80 o más Años , Fenómenos Biomecánicos , Recuento de Células , Córnea/anatomía & histología , Paquimetría Corneal , Técnicas de Diagnóstico Oftalmológico , Endotelio Corneal/anatomía & histología , Epitelio Corneal/fisiología , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia , Tomografía de Coherencia Óptica , Adulto JovenRESUMEN
To examine the relevance of concentration of benzalkonium chloride (BAK) on the cornea, we investigated the effects of latanoprost containing BAK alone and in combination with other antiglaucoma drug classes on corneal epithelium in vitro in a cultured rabbit corneal cell line (SIRC) and in vivo, using a corneal resistance device (CRD). [In vitro] staten's seruminstitut rabbit corneal cells were exposed to 0.005% latanoprost for 30s, followed by either phosphate buffered saline (control), 0.1% brimonidine, 0.5% timolol, 1% dorzolamide, or 1% brinzolamide. The number of viable cells was counted at 8, 15, and 30min. [In vivo] Albino rabbits were administered one drop of 0.005% latanoprost, followed 5min later by one drop of an agent from the in vitro trial. This was repeated every 15min for a total of three times. The change in corneal barrier function was assessed by measuring the corneal resistance at 2 and 30min after the final administration. [In vitro] At 8min, the viable cell count in the latanoprost+dorzolamide group was significantly lower than in the control group. At 15 and 30min, all treatment groups, except the latanoprost+brimonidine group, demonstrated significantly lower viable cell counts than the control group. [In vivo] At 2min after the final eye drop, the latanoprost+timolol group and the latanoprost+brinzolamide group demonstrated significantly lower corneal resistance than did the latanoprost+brimonidine group. No significant difference was observed between the agents at 30min. In conclusion, when combining latanoprost containing benzalkonium chloride with other classes of antiglaucoma drugs, brimonidine may cause the least corneal damage, and the number of drug administrations may be an important factor.
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Soluciones Oftálmicas/efectos adversos , Prostaglandinas F Sintéticas/farmacología , Seguridad , Animales , Tartrato de Brimonidina/efectos adversos , Supervivencia Celular/efectos de los fármacos , Impedancia Eléctrica , Epitelio Corneal/citología , Epitelio Corneal/efectos de los fármacos , Presión Intraocular/efectos de los fármacos , Latanoprost , Masculino , Conejos , Sulfonamidas/efectos adversos , Tiazinas/efectos adversos , Tiofenos/efectos adversos , Timolol/efectos adversosRESUMEN
PURPOSE: To evaluate the effects of fluoroquinolone-based antibacterial ophthalmic solutions on cell proliferation in vitro and corneal wound healing in vivo. METHODS: Staten's Serum institute rabbit corneal cells were exposed to phosphate-buffered saline, 1.5% and 0.5% levofloxacin, 0.5% moxifloxacin, and 0.3% gatifloxacin, for 2 min, following which the cells were incubated without the drug. The cell viability was evaluated after 24 or 72 h of incubation. Rabbit corneal epithelial abrasion models created using n-heptanol were instilled with saline or fluoroquinolone-based solutions 7 times at 30-min intervals, following which corneal epithelial wound healing was evaluated from 30 min to 48 h by the measurement of electrical corneal resistance (CR) ratios. RESULTS: The cell viability decreased over time; the lowest values were observed with 1.5% levofloxacin. Significant differences in cell viability were observed among the 4 solutions at 72 h (P<0.05); the cell viabilities of 1.5% and 0.5% levofloxacin, 0.5% moxifloxacin, and 0.3% gatifloxacin were 21.6%, 97.9%, 39.1%, and 67.5%, respectively. The electrical CR ratios at 48 h after instillation were 103.8% (saline), 78.2% (1.5% levofloxacin), 105.0% (0.5% levofloxacin), 74.9% (0.5% moxifloxacin), and 87.7% (0.3% gatifloxacin); the difference was significant between 1.5% levofloxacin or 0.5% moxifloxacin and saline (P<0.05). CONCLUSIONS: The cytotoxicities of 1.5% and 0.5% levofloxacin, 0.5% moxifloxacin, and 0.3% gatifloxacin were different, and 1.5% levofloxacin and 0.5% moxifloxacin resulted in delayed corneal wound healing. The results suggest that 1.5% levofloxacin exerts the greatest influence on corneal wound healing.
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Antibacterianos/farmacología , Lesiones de la Cornea/tratamiento farmacológico , Fluoroquinolonas/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Lesiones de la Cornea/patología , Modelos Animales de Enfermedad , Epitelio Corneal/efectos de los fármacos , Epitelio Corneal/patología , Gatifloxacina , Levofloxacino/farmacología , Moxifloxacino , Soluciones Oftálmicas , Conejos , Factores de TiempoRESUMEN
PURPOSE: We investigated the transcorneal penetration of commercial ophthalmic formulations containing timolol maleate in rabbit eyes. METHODS: One drop (30 µL) of each ophthalmic solution (Xalacom(®), DuoTrav(®), Cosopt(®), and Timoptol(®)) was administered to the conjunctival sac of the rabbits' eyes and the timolol maleate aqueous humor concentration was measured by high-performance liquid chromatography 15, 60, 120, and 240 min after the completion of administration. The effect of timolol ophthalmic solution pH (5.7-6.8) on ocular penetration was also examined. RESULTS: The concentration [Cmax (µg/mL)] of timolol maleate, found in each of the 4 ophthalmic solutions, penetrated to the aqueous humor was as follows: DuoTrav>Cosopt>Timoptol>Xalacom. The concentration of timolol maleate penetrated to the aqueous humor was highest with solutions in the vicinity of pH 6.8. CONCLUSIONS: The concentration of timolol maleate penetrated to the aqueous humor was highest in DuoTrav followed by Cosopt, Timoptol, and Xalacom, and the pH and Benzalkonium chloride (BAK) concentration of the ophthalmic solution were believed to be factors that influenced this phenomena.
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Córnea/metabolismo , Ojo/metabolismo , Timolol/administración & dosificación , Timolol/farmacocinética , Animales , Compuestos de Benzalconio/administración & dosificación , Compuestos de Benzalconio/farmacocinética , Cromatografía Liquida/métodos , Cloprostenol/administración & dosificación , Cloprostenol/análogos & derivados , Cloprostenol/farmacocinética , Córnea/efectos de los fármacos , Combinación de Medicamentos , Ojo/efectos de los fármacos , Glaucoma/tratamiento farmacológico , Masculino , Soluciones Oftálmicas/administración & dosificación , Conservadores Farmacéuticos/administración & dosificación , Prostaglandinas F Sintéticas/administración & dosificación , Prostaglandinas F Sintéticas/farmacocinética , Conejos , Sulfonamidas/administración & dosificación , Sulfonamidas/farmacocinética , Tiofenos/administración & dosificación , Tiofenos/farmacocinéticaRESUMEN
Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by periodic fever and serosal inflammation. FMF is mostly reported in the Mediterranean region and is considered to be rare in Japan with estimated 292 cases. We treated three unrelated FMF patients in one year in a city with 144,000 residents. Two of the three patients were over 70 years old. FMF may therefore be underdiagnosed in Japan.
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Errores Diagnósticos , Fiebre Mediterránea Familiar/diagnóstico , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X/métodos , Anciano , Anciano de 80 o más Años , Diagnóstico Diferencial , Femenino , Humanos , Japón , Persona de Mediana EdadRESUMEN
The authors previously reported that the visit-to-visit variability of blood pressure is correlated with renal function decline in nondiabetic chronic kidney disease. Little is known about the association between visit-to-visit variability and renal function decline in patients with diabetic chronic kidney disease. The authors retrospectively studied 69 patients with diabetic chronic kidney disease stage 3a, 3b, or 4. The standard deviation and coefficient of variation of blood pressure in 12 consecutive visits were defined as visit-to-visit variability of blood pressure. The median observation period was 32 months. In univariate correlation, the standard deviation and coefficient of variation of blood pressure were not significantly associated with the slope of estimated glomerular filtration rate. There was no significant association between the visit-to-visit variability of blood pressure and renal function decline in patients with diabetic chronic kidney disease, in contrast with our previous study of nondiabetic patients with chronic kidney disease.
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Presión Sanguínea/fisiología , Nefropatías Diabéticas/fisiopatología , Tasa de Filtración Glomerular/fisiología , Hipertensión/etiología , Riñón/fisiopatología , Visita a Consultorio Médico , Anciano , Enfermedad Crónica , Nefropatías Diabéticas/complicaciones , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/fisiopatología , Masculino , Pronóstico , Estudios RetrospectivosRESUMEN
PURPOSE: To investigate the safety of five types of antiglaucoma prostaglandin analog ophthalmic formulations, and to clarify their differences in accordance with contained additives (preservatives and surface-active agents). METHODS: THE FOLLOWING FIVE TYPES OF OPHTHALMIC SOLUTIONS AND THREE TYPES OF ADDITIVES WERE INVESTIGATED: latanoprost (Xalatan(®); latanoprost), tafluprost (Tapros(®); tafluprost), bimatoprost (Lumigan(®); bimatoprost), travoprost (Travatan(®); travoprost), travoprost (Travatan Z(®); travoprost-Z), benzalkonium chloride (BAK), polyoxyethylene hardening castor oil 40 (HCO-40), and polysorbate 80 (P-80). These experimental solutions were exposed to the cultured cells of a rabbit-derived corneal cell line for a certain time, and the exposure time causing 50% cell damage (CD50), indicated by the ratio of viable cells to total cells was calculated (in vitro). In addition, corneal resistance (CR) was measured and CR ratio (post-treatment CR/pretreatment CR × 100) was calculated (in vivo). RESULTS: CD50 of each ophthalmic solution was the longest with tafluprost, followed by travoprost-Z, bimatoprost, travoprost, and latanoprost. CD50 of 0.005%, 0.01%, and 0.02% BAK was 14.5 minutes, 8.1 minutes, and 4.0 minutes, respectively. The number of viable cells decreased to 60%, 8 minutes after exposure with HCO-40, and 30 minutes after being exposed to P-80. The CR ratio was 81.0% with travoprost and 82.0% with latanoprost, indicating a significant posttreatment reduction of CR (P < 0.05). The CR ratio did not decrease after treatment with tafluprost, travoprost-Z, or bimatoprost. The CR ratio of 0.005%, 0.01%, and 0.02% BAK was 105.0%, 90.5%, and 68.7%, respectively, and that of HCO-40 and P-80 was 108.7% and 114.2%, respectively. CONCLUSION: BAK, HCO-40, and P-80 were thought to be involved in corneal injuries caused by each ophthalmic solution. Corneal injuries due to surface action were observed when using HCO-40 and P-80. When HCO-40 was combined with BAK, it induced micellar BAK and reduced corneal injuries by BAK.
RESUMEN
An association between visit-to-visit variability (VVV) of blood pressure (BP) and renal damage was recently reported in a cross-sectional study. We aimed to clarify the longitudinal effect of VVV of BP on deterioration of renal function in patients with non-diabetic chronic kidney disease (CKD). We retrospectively studied 56 patients with non-diabetic CKD (stage 3 or 4) who visited our nephrology clinic between September 1994 and May 2011. VVV of BP was defined as the standard deviation and coefficient of variation (CV) of office BP measured at 12 consecutive visits. Main outcomes were the annual decline in the estimated glomerular filtration rate (eGFR) and the composite renal end point defined as a doubling of serum creatinine or the need for dialysis. The median observation period was 83 months. Standard deviation and CV of office systolic BP (SBP) were significantly associated with the slope of the eGFR after adjustments for confounders. The adjusted risk for composite renal end points more than doubled for each increment of 1-standard deviation of the standard deviation of office SBP (hazard ratio (HR) 2.20, P=0.001), and for each increment of 1-standard deviation of the CV of office SBP (HR 2.12, P=0.002). The present study demonstrated that the visit-to-visit variability of BP is an independent determinant of deterioration of renal function in patients with non-diabetic CKD.
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Presión Sanguínea/fisiología , Riñón/fisiopatología , Visita a Consultorio Médico/estadística & datos numéricos , Insuficiencia Renal Crónica/fisiopatología , Anciano , Anciano de 80 o más Años , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Creatinina/sangre , Estudios Transversales , Femenino , Tasa de Filtración Glomerular/fisiología , Humanos , Hipertensión/fisiopatología , Hipertensión/prevención & control , Masculino , Persona de Mediana Edad , Análisis de Regresión , Estudios RetrospectivosRESUMEN
PURPOSE: We attempted to develop a device for measuring electrical corneal resistance (CR) using corneal contact lens electrodes to quantitatively evaluate corneal injury in vivo. In the present study, full-thickness detachment of the corneal epithelium was induced by n-heptanol, and the feasibility of the quantitative evaluation of this injury by corneal contact lens electrodes was evaluated in vivo. METHODS: The central area of an albino rabbit's cornea was exposed to a filter paper pre-immersed in n-heptanol for 1 minute to induce injury of the corneal epithelium. After induction of injury, the electrical CR was measured and the percentage of CR (%CR) was calculated. Fluorescein solution (3 µL) was applied to the wound/affected area of the corneal epithelium for photography with a slit-lamp biomicroscope. The wound/affected area was measured using an image analysis system. The correlation between the %CR and the wound/affected area was analyzed. RESULTS: As the size of the wound/affected area of the corneal epithelium increased, the %CR decreased after corneal epithelium detachment. Thus, a close correlation was found between the area of corneal epithelium detachment and the %CR. CONCLUSION: The corneal resistance device that we developed was capable of quantitatively evaluating n-heptanol-induced full-thickness injuries of the corneal epithelium.
RESUMEN
AIM: It was the aim of this study to compare the pharmacokinetics of moxifloxacin (MFLX) hydrochloride in rabbits after topical and oral administration. METHODS: Three 50-µl applications of MFLX (0.5%) topical ophthalmic solution were instilled into the cul-de-sac of New Zealand white rabbits at 15-min intervals. Aqueous and vitreous samples were collected and analyzed 30-240 min after the final instillation. Assays were performed using high-performance liquid chromatography. MFLX (16 mg/kg of body weight) was administered orally. Drug concentrations in aqueous, vitreous and serum samples, collected at 30-360 min after administration, were determined using high-performance liquid chromatography. RESULTS: After topical administration, the maximum concentrations of MFLX in the aqueous and vitreous samples were 10.2 ± 1.6 µg/ml (30 min; n = 6) and 0.10 ± 0.03 µg/ml (30 min; n = 6), respectively. After oral administration, the maximum concentrations in the aqueous, vitreous and serum samples were 0.9 ± 0.3 µg/ml (120 min; n = 6), 0.7 ± 0.2 µg/ml (240 min; n = 6) and 1.6 ± 0.9 µg/ml (120 min; n = 6), respectively. The percentages of serum MFLX concentration in the aqueous and vitreous samples after oral administration were 55.2 and 41.7%, respectively. CONCLUSIONS: The aqueous concentration of MFLX was about 10-fold higher after topical than after oral administration. However, intravitreal MFLX concentrations after oral administration were about 7-fold higher than those after topical administration. The MFLX concentrations in the aqueous humor following oral administration exceeded the minimum inhibitory concentration for 90% of the bacteria involved in ocular infection.
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Antiinfecciosos/farmacocinética , Humor Acuoso/metabolismo , Compuestos Aza/farmacocinética , Quinolinas/farmacocinética , Cuerpo Vítreo/metabolismo , Administración Oral , Administración Tópica , Animales , Antiinfecciosos/administración & dosificación , Compuestos Aza/administración & dosificación , Cromatografía Líquida de Alta Presión , Fluoroquinolonas , Moxifloxacino , Soluciones Oftálmicas/administración & dosificación , Soluciones Oftálmicas/farmacocinética , Quinolinas/administración & dosificación , ConejosRESUMEN
PURPOSE: After measuring the pharmacokinetic parameters of five fluoroquinolone ophthalmic solutions, we utilized the obtained indices to try to predict the clinical effects of antimicrobial ophthalmic solutions and apply the characteristics to the index for inhibition of resistant bacteria. METHODS: Each ophthalmic solution was instilled in white rabbit eyes 3 times every 15 min and the anterior chamber aqueous humor was collected 10, 30, 60, 120, and 240 min after instillation. Drug concentrations were measured by high-performance liquid chromatography (HPLC) to determine the maximum aqueous concentration (AQCmax) of each drug by using a 1-compartment model. RESULTS: Moxifloxacin (MFLX) had the highest AQCmax, 9.04 microg/mL, among the five drugs, followed by levofloxacin (LVFX, 2.65 microg/mL), gatifloxacin (GFLX, 1.26 microg/mL), ofloxacin (OFLX, 0.89 microg/mL), and tosufloxacin (TFLX, 0.42 microg/mL) in descending order of AQCmax. Furthermore, the AQCmax/MPC (mutant prevention concentration) against Staphylococcus aureus was 15.07 and 1.06 for MFLX and LVFX, respectively. The AQCmax/MPC against Streptococcus pneumoniae was 18.08 and 1.15 for MFLX and LVFX, respectively. CONCLUSIONS: From these results, we can expect that the MFLX ophthalmic solution will be a sufficiently effective therapeutic agent in the treatment of eye infection, prevention of postoperative endophthalmitis, and prevention of drug resistance.
Asunto(s)
Antibacterianos/farmacocinética , Animales , Antibacterianos/administración & dosificación , Humor Acuoso/metabolismo , Cromatografía Líquida de Alta Presión/métodos , Farmacorresistencia Bacteriana , Infecciones Bacterianas del Ojo/tratamiento farmacológico , Fluoroquinolonas/administración & dosificación , Fluoroquinolonas/farmacocinética , Masculino , Pruebas de Sensibilidad Microbiana , Soluciones Oftálmicas , Conejos , Staphylococcus aureus/efectos de los fármacos , Streptococcus pneumoniae/efectos de los fármacos , Factores de TiempoRESUMEN
UNLABELLED: ABSTRACT Objective: Ocular tissue penetration of five different ophthalmic fluoroquinolone solutions in the rabbit eye was measured and evaluated by an index of the maximum aqueous concentration (AQCmax). METHODS: Moxifloxacin 0.5% (MFLX), levofloxacin 0.5% (LVFX), gatifloxacin 0.3% (GFLX), ofloxacin 0.3% (OFLX), or tosufloxacin tosilate 0.3% (TFLX) were instilled into the eyes of white rabbits every 15 min for a total of three doses. Aqueous humor, cornea, iris/ciliary body and vitreous body were collected 10 to 240 min after instillation and drug concentrations were measured by high-performance liquid chromatography. RESULTS: The concentration of MFLX was the highest in each tissue, with maximum concentrations of MFLX in the aqueous humor (10.16 +/- 1.59 microg/mL) at 30 min after instillation, cornea (156.07 +/- 95.97 microg/g) and iris/ciliary body (11.92 +/- 4.00 microg/g) at 10 min after instillation, and vitreous body (0.099 +/- 0.033 microg/mL) at 30 min after instillation. The concentration of TFLX was the lowest in each tissue, with LVFX, GFLX, and OFLX sharing the mid-ranks. AQCmax : MIC(90) ratio for S. aureus was 150.67 for MFLX, 10.6 for LVFX, 9.69 for GFLX, 3.48 for OFLX, and could not be determined for TFLX. CONCLUSION: AQCmax is a useful pharmacokinetic parameter for determining the therapeutic efficacy of an ophthalmic antibiotic, especially when combined with MIC(90) values for intraocular pathogens. C(max) of MFLX ophthalmic solution was superior in all tissues (cornea, aqueous humor, iris/ciliary body and vitreous body) among the five ophthalmic solutions studied, exceeding the MIC(90) of S. aureus in all tissues, and MIC(90)s of S. epidermidis, B. cereus, and P. acnes in aqueous humor, cornea, and iris/ciliary body. AQCmax was approximately proportional to C(max) in iris/ciliary body and vitreous, and may be used in combination with MIC(90)s as an index to predict the most appropriate dose and frequency of ophthalmic antibiotics in conjunction with other PK/PD parameters. This study may provide the groundwork for calculation of AQCmax in humans.
Asunto(s)
Antibacterianos/farmacocinética , Fluoroquinolonas/farmacocinética , Soluciones Oftálmicas/farmacocinética , Animales , Antibacterianos/farmacología , Relación Dosis-Respuesta a Droga , Ojo/metabolismo , Ojo/microbiología , Infecciones Bacterianas del Ojo/tratamiento farmacológico , Fluoroquinolonas/farmacología , Soluciones Oftálmicas/farmacología , Conejos , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureusRESUMEN
PURPOSE: Moxifloxacin, a fourth-generation fluoroquinolone (FQ), was compared to levofloxacin, a third-generation FQ, for preventing FQ-resistant, methicillin-resistant Staphylococcus aureus (FQrMRSA) endophthalmitis in a rabbit model. METHODS: Three regimens of topical treatments (moxifloxacin 0.5%, levofloxacin 0.5%, and saline) were tested to prevent endophthalmitis. For each regimen, drops were instilled every 15 min for 1 h into the left eyes of 15 rabbits. After anesthesia, 2 x 10(4) cfu of FQrMRSA was injected into the aqueous. One drop of treatment was given immediately, and another four drops were applied over 24 h. At 24 h, the eyes were clinically graded for endophthalmitis. After the rabbits were sacrificed, the aqueous and vitreous were tapped for bacterial colony counts. RESULTS: Topical moxifloxacin (12/15, 80%) significantly (P=0.0001) prevented clinical endophthalmitis in more rabbits than levofloxacin (2/15, 13%) or saline (2/15, 13%). The total median clinical score for moxifloxacin treatment (1.0) was significantly (P=0.0004) lower than that for levofloxacin (20.0) or saline (23.0). Culture-negative eyes were less frequent for levofloxacin (8/15, 53%) and saline (1/15, 7%) treatments than for moxifloxacin treatment (12/15, 80%). CONCLUSION: This in vivo study indicates that moxifloxacin, a fourth-generation FQ, may be more effective than levofloxacin, a third-generation FQ, in preventing experimental FQrMRSA. endophthalmitis.
Asunto(s)
Antibacterianos/farmacología , Compuestos Aza/farmacología , Farmacorresistencia Bacteriana Múltiple , Endoftalmitis/prevención & control , Infecciones Bacterianas del Ojo/prevención & control , Levofloxacino , Ofloxacino/farmacología , Quinolinas/farmacología , Infecciones Estafilocócicas/prevención & control , Staphylococcus aureus/efectos de los fármacos , Administración Tópica , Animales , Humor Acuoso/microbiología , Recuento de Colonia Microbiana , Modelos Animales de Enfermedad , Endoftalmitis/microbiología , Infecciones Bacterianas del Ojo/microbiología , Fluoroquinolonas/farmacología , Meticilina/farmacología , Moxifloxacino , Conejos , Infecciones Estafilocócicas/microbiología , Cuerpo Vítreo/microbiologíaAsunto(s)
Antipsicóticos/efectos adversos , Hipertrigliceridemia/inducido químicamente , Lipoproteína Lipasa/deficiencia , Adolescente , Antipsicóticos/uso terapéutico , Benzodiazepinas/efectos adversos , Benzodiazepinas/uso terapéutico , Humanos , Masculino , Olanzapina , Factores de Riesgo , Esquizofrenia/tratamiento farmacológicoRESUMEN
PURPOSE: In this study, we measured the cefotiam dihydrochloride (CTM) concentration in ocular tissue after filtration surgery in rabbit eyes. METHODS: CTM (20 mg/kg body weight) was administered intravenously 30 min before filtration surgery which was performed by double flap procedure on the right eyes of white rabbits. The aqueous humor and serum were extracted at 10 min after surgery and at 30 min, 60 min, and 120 min. Drug concentration in all of the specimens was measured by high performance liquid chromatography (HP-LC). RESULT: The CTM concentrations of aqueous humor in the nonoperated eyes were 0.44 +/- 0.16(mean +/- standard deviation) microg/ml (n = 4) (40 min after intravenous dosage), 0.36 +/- 0.17microg/ml (n = 4) (60 min after intravenous dosage), 0.38 +/- 0.34, microg/ml(n = 3) (90min after intravenous dosage) and 0.27 +/- 0.10 microg/ml (n = 5) (150 min after intravenous dosage). In contrast, CTM concentration in the aqueous humor of the operated eyes was 2.4 +/- 0.95 microg/ml (n = 4) at 10 min after surgery (40 min after intravenous dosage), 2.11 +/- 1.10 microg/ml (n = 4) at 30 min after surgery (60 min after intravenous dosage), 1.18 +/- 0.78 microg/ml (n = 4) at 60 min after surgery (90 min after intravenous dosage) and 0.47 +/- 0.1 microg/ml (n = 5) at 120 min after surgery (150 min after intravenous dosage). The intraocular penetration of CTM at 10 min and at 120 min after filtration surgery was significantly higher in comparison with the drug concentration in the nonoperated eyes (p < 0.05). CONCLUSION: The intraocular penetration of CTM after filtration surgery was much higher in comparison with the drug concentration in the nonoperated eyes. These results may be useful to predict the intraocular penetration of CTM in human eyes after filtration surgery.