RESUMO
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.
Assuntos
Compostos Férricos , Hepcidinas , Humanos , Compostos Férricos/farmacologia , Ferritinas , Ferro , Estudos Prospectivos , Diálise RenalRESUMO
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.
Assuntos
Alanina/análogos & derivados , Antioxidantes/farmacologia , Compostos de Benzalcônio/farmacologia , Epitélio Corneano/efeitos dos fármacos , Epitélio Corneano/lesões , Conservantes Farmacêuticos/farmacologia , Quinolonas/farmacologia , Alanina/farmacologia , Animais , Quimioterapia Combinada , Latanoprosta/farmacologia , Masculino , Coelhos , Distribuição AleatóriaRESUMO
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.
Assuntos
Anti-Infecciosos/farmacocinética , Humor Aquoso/metabolismo , Compostos Aza/farmacocinética , Quinolinas/farmacocinética , Corpo Vítreo/metabolismo , Administração Oral , Administração Tópica , Animais , Anti-Infecciosos/administração & dosagem , Compostos Aza/administração & dosagem , Cromatografia Líquida de Alta Pressão , Fluoroquinolonas , Moxifloxacina , Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/farmacocinética , Quinolinas/administração & dosagem , CoelhosRESUMO
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.
Assuntos
Anti-Hipertensivos/uso terapêutico , Córnea/efeitos dos fármacos , Impedância Elétrica , Soluções Oftálmicas/uso terapêutico , Animais , Glaucoma/tratamento farmacológico , Masculino , CoelhosRESUMO
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.
Assuntos
Antibacterianos/farmacologia , Compostos Aza/farmacologia , Farmacorresistência Bacteriana Múltipla , Endoftalmite/prevenção & controle , Infecções Oculares Bacterianas/prevenção & controle , Levofloxacino , Ofloxacino/farmacologia , Quinolinas/farmacologia , Infecções Estafilocócicas/prevenção & controle , Staphylococcus aureus/efeitos dos fármacos , Administração Tópica , Animais , Humor Aquoso/microbiologia , Contagem de Colônia Microbiana , Modelos Animais de Doenças , Endoftalmite/microbiologia , Infecções Oculares Bacterianas/microbiologia , Fluoroquinolonas/farmacologia , Meticilina/farmacologia , Moxifloxacina , Coelhos , Infecções Estafilocócicas/microbiologia , Corpo Vítreo/microbiologiaRESUMO
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.
Assuntos
Alanina/análogos & derivados , Lesões da Córnea/induzido quimicamente , Lesões da Córnea/tratamento farmacológico , Epitélio Corneano/efeitos dos fármacos , Epitélio Corneano/lesões , Iodo/efeitos adversos , Álcool de Polivinil/efeitos adversos , Substâncias Protetoras/uso terapêutico , Quinolonas/uso terapêutico , Administração Oftálmica , Alanina/administração & dosagem , Alanina/uso terapêutico , Animais , Antioxidantes/administração & dosagem , Antioxidantes/uso terapêutico , Lesões da Córnea/patologia , Lesões da Córnea/prevenção & controle , Epitélio Corneano/patologia , Masculino , Substâncias Protetoras/administração & dosagem , Quinolonas/administração & dosagem , CoelhosRESUMO
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.
Assuntos
Injúria Renal Aguda/diagnóstico , Malation/toxicidade , Síndrome Nefrótica/diagnóstico , Praguicidas/toxicidade , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/complicações , Injúria Renal Aguda/terapia , Idoso , Diagnóstico Diferencial , Humanos , Masculino , Síndrome Nefrótica/induzido quimicamente , Síndrome Nefrótica/complicações , Síndrome Nefrótica/terapia , Diálise RenalRESUMO
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.
Assuntos
Córnea/fisiologia , Impedância Elétrica , Adulto , Idoso , Idoso de 80 Anos ou mais , Fenômenos Biomecânicos , Contagem de Células , Córnea/anatomia & histologia , Paquimetria Corneana , Técnicas de Diagnóstico Oftalmológico , Endotélio Corneano/anatomia & histologia , Epitélio Corneano/fisiologia , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Tomografia de Coerência Óptica , Adulto JovemRESUMO
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.
Assuntos
Soluções Oftálmicas/efeitos adversos , Prostaglandinas F Sintéticas/farmacologia , Segurança , Animais , Tartarato de Brimonidina/efeitos adversos , Sobrevivência Celular/efeitos dos fármacos , Impedância Elétrica , Epitélio Corneano/citologia , Epitélio Corneano/efeitos dos fármacos , Pressão Intraocular/efeitos dos fármacos , Latanoprosta , Masculino , Coelhos , Sulfonamidas/efeitos adversos , Tiazinas/efeitos adversos , Tiofenos/efeitos adversos , Timolol/efeitos adversosRESUMO
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.
Assuntos
Antibacterianos/farmacocinética , Humor Aquoso/metabolismo , Cefotiam/farmacocinética , Olho/metabolismo , Cirurgia Filtrante , Animais , Cromatografia Líquida de Alta Pressão , Injeções Intravenosas , CoelhosRESUMO
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.
Assuntos
Córnea/metabolismo , Olho/metabolismo , Timolol/administração & dosagem , Timolol/farmacocinética , Animais , Compostos de Benzalcônio/administração & dosagem , Compostos de Benzalcônio/farmacocinética , Cromatografia Líquida/métodos , Cloprostenol/administração & dosagem , Cloprostenol/análogos & derivados , Cloprostenol/farmacocinética , Córnea/efeitos dos fármacos , Combinação de Medicamentos , Olho/efeitos dos fármacos , Glaucoma/tratamento farmacológico , Masculino , Soluções Oftálmicas/administração & dosagem , Conservantes Farmacêuticos/administração & dosagem , Prostaglandinas F Sintéticas/administração & dosagem , Prostaglandinas F Sintéticas/farmacocinética , Coelhos , Sulfonamidas/administração & dosagem , Sulfonamidas/farmacocinética , Tiofenos/administração & dosagem , Tiofenos/farmacocinéticaRESUMO
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.
Assuntos
Antibacterianos/farmacologia , Lesões da Córnea/tratamento farmacológico , Fluoroquinolonas/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Lesões da Córnea/patologia , Modelos Animais de Doenças , Epitélio Corneano/efeitos dos fármacos , Epitélio Corneano/patologia , Gatifloxacina , Levofloxacino/farmacologia , Moxifloxacina , Soluções Oftálmicas , Coelhos , Fatores de TempoRESUMO
PURPOSE: In order to determine whether the one-component method for calculating drug concentration in the aqueous (AQC(max)) is useful for selecting an appropriate ophthalmic solution, six general purpose antimicrobial ophthalmic solutions already on the market were investigated. METHODS: The drugs examined were levofloxacin (LVFX), chloramphenicol (CP), erythromycin lactobionate (EM), micronomicin sulfate (MCR), cefmenoxime hydrochloride (CMX), and disodium sulfobenzyl penicillin (SBPC). Fifty microliters of each solution was instilled into the cul-de-sac of New Zealand White rabbit eyes three times at 15-minute intervals. The drug concentrations in the aqueous humor 10, 30, 60, 120, and 240 minutes after the final instillation were examined by high performance liquid chromatography (HPLC) and/or bioassay. The AQC(max) was calculated using the one-compartment method. RESULTS: The calculated AQC(max) was 2.5 microg/mL (HPLC method) and 2.28 microg/mL (bioassay method) for LVFX, 2.17 microg/mL for CP, and 0.45 microg/mL for EM. The AQC(max) for CMX, MCR, and SBPC could not be calculated by the one-compartment method. CONCLUSIONS: The AQC(max) of LVFX was higher than that of the two other general purpose antimicrobial ophthalmic solutions. The AQC(max) of these drugs might be a useful parameter for selecting an appropriate ophthalmic solution for the treatment of infected eyes.
Assuntos
Antibacterianos/farmacocinética , Humor Aquoso/metabolismo , Soluções Oftálmicas/farmacocinética , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Masculino , Testes de Sensibilidade Microbiana , Soluções Oftálmicas/química , Soluções Oftálmicas/farmacologia , CoelhosRESUMO
PURPOSE: Pharmacokinetic studies of antibacterial agents for infectious eye diseases have usually been performed on normal rabbit eyes. In this study, the intraocular penetration of fluoroquinolone ophthalmic solutions was determined in normal rabbit eyes and in rabbit eyes that had the corneal epithelium intentionally removed. METHODS: We determined the intraocular penetration of ofloxacin (OFLX), levofloxacin (LVFX), and norfloxacin (NFLX), fluoroquinolone ophthalmic solutions that are already on the market and undergoing clinical studies, by injecting 50 microl of each solution into the cul-de-sacs of rabbit eyes three times at 15-min intervals. The drug concentration at 10, 30, 60, 120, and 240 min after final instillation was determined by high-performance liquid chromatography. RESULTS: The maximum concentration in the aqueous humor of normal rabbit eyes was 2.09 +/- 1.56 microg/ml (60 min, OFLX), 2.57 +/- 1.00 microg/ml (30 min, LVFX), and 0.42 +/- 0.12 microg/ml (120 min, NFLX). The drug concentration in the aqueous humor of eyes with intentionally removed corneal epithelium was 12.50 +/- 5.62 microg/ml (30 min, OFLX), 9.02 +/- 2.45 microg/ml (60 min, LVFX), and 8.54 +/- 5.17 microg/ml (30 min, NFLX). The drug penetration of the eye drops into eyes with removed corneal epithelium was around 6 times (OFLX), 3.5 times (LVFX), and 20 times (NFLX) higher than the penetration into the eye with normal cornea. CONCLUSION: Among the pharmacokinetic parameters of the three ophthalmic solutions according to the one-compartment model, the maximum concentration in the aqueous and the area under the concentration-time curve in the aqueous tended to be higher in the eyes with intentionally removed corneal epithelia than in those with normal corneas.
Assuntos
Anti-Infecciosos/farmacocinética , Humor Aquoso/metabolismo , Córnea/metabolismo , Epitélio Corneano/fisiologia , Fluoroquinolonas/farmacocinética , Animais , Área Sob a Curva , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Levofloxacino , Masculino , Norfloxacino/farmacocinética , Ofloxacino/farmacocinética , Soluções Oftálmicas/farmacocinética , CoelhosRESUMO
PURPOSE: In order to determine whether the one-component method for calculating drug concentration in the aqueous(AQCmax) is useful for selecting an appropriate ophthalmic solution, 6 general purpose antimicrobial ophthalmic solutions already on the market were investigated. METHODS: The drugs examined were levofloxacin (LVFX), chloramphenicol(CP), erythromycin lactobionate(EM), micronomicin sulfate(MCR), cefmenoxime hydrochloride(CMX) and disodium sufobenzyl penicillin(SBPC). Fifty microliters of each solutions was instilled into the cul-de-sac of New Zealand White rabbit eyes 3 times at 15-minute intervals. The drug concentrations in(the anterior sac aqueous,: this is wrong) the aqueous humor 10, 30, 60, 120 and 240 minutes after the final instillation were examined by high performance liquid chromatography(HPLC) and/or bioassay. The AQCmax was calculated using the one-compartment method. RESULTS: The calculated AQCmax was 2.5 micrograms/ml (HPLC method) and 2.28 micrograms/ml (Bioassay Method) for LVFX, 2.17 micrograms/ml for CP, and 0.45 microgram/ml for EM. The AQCmax for CMX, MCR and SBPC could not be calculated by the one-compartment method. CONCLUSION: The AQCmax of LVFX was higher than that of the 2 other general purpose antimicrobial ophthalmic solutions. The AQCmax of these drugs might be a useful parameter for selecting an appropriate ophthalmic solution for the treatment of infected eyes.
Assuntos
Aminoglicosídeos , Antibacterianos/farmacocinética , Humor Aquoso/química , Eritromicina/análogos & derivados , Soluções Oftálmicas/farmacocinética , Animais , Cefmenoxima/farmacocinética , Cloranfenicol/farmacocinética , Eritromicina/farmacocinética , Gentamicinas , Levofloxacino , Ofloxacino/farmacocinética , Coelhos , Sulbenicilina/farmacocinéticaRESUMO
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.
Assuntos
Pressão Sanguínea/fisiologia , Nefropatias Diabéticas/fisiopatologia , Taxa de Filtração Glomerular/fisiologia , Hipertensão/etiologia , Rim/fisiopatologia , Visita a Consultório Médico , Idoso , Doença Crônica , Nefropatias Diabéticas/complicações , Progressão da Doença , Feminino , Seguimentos , Humanos , Hipertensão/fisiopatologia , Masculino , Prognóstico , Estudos RetrospectivosRESUMO
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.
Assuntos
Erros de Diagnóstico , Febre Familiar do Mediterrâneo/diagnóstico , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Japão , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Pressão Sanguínea/fisiologia , Rim/fisiopatologia , Visita a Consultório Médico/estatística & dados numéricos , Insuficiência Renal Crônica/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Creatinina/sangue , Estudos Transversais , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Hipertensão/fisiopatologia , Hipertensão/prevenção & controle , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Estudos RetrospectivosRESUMO
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.
RESUMO
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.