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Biomedical subjects

Y Shirao

Publications and source records attributed to Y Shirao.

At least 19 recordsLinked to original sources

Electrical responses from diabetic retina.

Diabetic retinopathy has long been considered to be a retinal manifestation of systemic diabetic angiopathy. Indeed, it is therapeutically true. However, the prolongation of OP peak latency in diabetic eyes without any angiographic evidence of angiopathy leads us to presume that certain neuronal disorders occur early in diabetic eyes. Even though we cannot neglect the possibility that the prolongation of the OP peak latency may derive from undetectable retinal hypoperfusion, it is still far from conventional diabetic angiopathy. Rather, the status should be properly termed "intraretinal diabetic neuropathy" in that the neurones are the disturbed cells to cause visual dysfunction. Thereafter, the OP amplitude diminishes as retinopathy advances, probably depending on the degree of retinal circulatory disturbance. Marked diminution of the OP amplitude predicts rapid progression and poor prognosis of retinopathy. Diabetic retinal pigment epitheliopathy as manifested by one of our non-photic EOG responses is another kind of early ocular involvement of diabetes. Because its mechanisms are not yet known, so far we have not succeeded in correlating it to any kind of subjective visual index. Routine fundus inspection or fluorescent fundus angiography is incapable of detecting the compromised neural retina and/or retinal pigment epithelial integrity and thus the electrophysiology of vision has the edge in ophthalmology.

Animals

Upregulation of retinal vascular endothelial growth factor mRNAs in spontaneously diabetic rats without ophthalmoscopic retinopathy. A possible participation of advanced glycation end products in the development of the early phase of diabetic retinopathy.

Vascular endothelial growth factor (VEGF) has recently been shown to be involved in the pathogenesis of proliferative diabetic retinopathy. However, its involvement in the development of the early phase of diabetic retinopathy is not fully understood. In this study we investigated the retinal VEGF mRNA level in spontaneously diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats, a model of non-insulin-dependent diabetes, without overt retinopathy, using quantitative reverse-transcription polymerase chain reaction. The retinal VEGF mRNA level was 2.2 times higher (p < 0.0005) in OLETF rats than in control rats at the age of 60 weeks. Moreover, their retinal mRNA level was positively correlated with serum concentration of advanced glycation end products (AGEs) but not to serum glucose concentration. Furthermore, the peak latency of the oscillatory potentials in the electroretinogram, one of the most sensitive markers for the early phase of diabetic retinopathy, was significantly prolonged in OLETF rats (p < 0.05), being also correlated with the serum AGE concentration. The results thus suggest that AGEs, which are formed acceleratedly in diabetic conditions, are involved in the development of the early phase of diabetic retinopathy probably through the induction of retinal VEGF mRNAs.

Animals

Normal S cone electroretinogram b-wave in Oguchi's disease.

AIM: The short wavelength sensitive (S) cone electroretinograms (ERGs) were examined in two patients with Oguchi's disease to study S cone function. METHODS: Ganzfeld colour flashes under bright white background illumination were used to elicit S cone, and mixed long (L) and middle (M) wavelength sensitive cone ERGs. RESULTS: The S cone ERG b-wave was normal with short wavelength stimuli with normal L and M cone responses in both patients. CONCLUSIONS: These ERG results indicate that the S cone system as well as the L and M cone system is not defective in Oguchi's disease, while the S cone responses are not detectable in the complete type of congenital stationary night blindness as reported previously. The results imply that there is a significant difference in the way the S cone system is affected in different forms of stationary night blindness, and that the S cone and rod do not share the same arrestin system.

Adult

[Comparison of free non-tryptophan fluorescent substances in water-soluble fraction of brunescent and non-brunescent human cataract].

We compared the concentrations of protein-unbound non-tryptophan fluorescent substances in the water-soluble fraction between non-brunescent (NBr) and brunescent (Br) human cataractous lens nuclei. Lens nuclei (NBr, 22 eyes: Br, 9 eyes) from non-diabetic patients, obtained by extracapsular cataract extraction, were individually homogenized and centrifuged. The supernatants were subsequently ultra-dialyzed and assessed by high pressure liquid chromatography. 3-Hydroxykynurenine-O-beta-glucoside (3-HKG) as well as an unidentified fluorescent substance was detected. While the concentrations of the former substance did not significantly differ between the NBr and the Br nuclei (NBr, 0.55 +/- 0.49 mumol/g wet weight: Br, 0.90 +/- 0.64 mumol/g wet weight; p > 0.1), the concentration of the latter substance was significantly greater in the Br nuclei than in the NBr nuclei (NBr, 2.2 x 10(3) +/- 5.4 x 10(3) AU/g wet weight: Br, 1.4 x 10(5) +/- 1.1 x 10(5) AU/g wet weight; AU: area unit, p < 0.01). An incubation of the dialysate with beta-glucosidase eliminated the peak corresponding to the latter substance. These results suggest that an unidentified protein-unbound fluorescent substance, which is presumably a beta-glucoside, in the lens nuclei is related to the coloration of human lens nuclei.

Cataract

[Effects of retinal intrinsic dopamine on the in in vivo electroretinogram of rabbits].

The effects of intravitreal injection of nomifensine, a potent dopamine uptake blocker, on the electroretinogram (ERG) were investigated in rabbit. Nomifensine enhanced the amplitude of the oscillatory potentials at 100 microM (intravitreal concentration) and 300 microM (p < 0.05), but it attenuated the oscillatory potentials at 1,000 microM (p < 0.01). Nomifensine attenuated the amplitude of the scotopic b-wave at 100 microM and 1,000 microM (p < 0.05), leaving the peak latency of the scotopic b-wave unaltered at all concentrations tested (30, 100, 300, 500 and 1,000 microM). Neither the amplitude nor the peak latency of the dark-adapted a- and b-waves elicited by bright stimuli was altered at any nomifensine concentration tested. 1 microM dopamine and 30 microM nomifensine together, each of which is insufficient to alter either of the scotopic b-wave or the oscillatory potentials when applied alone, reduced the scotopic b-wave and enhanced the oscillatory potentials. These results suggest that intrinsic dopamine release in the retina is large enough to alter the ERG.

Animals

[D1 receptor mediates dopamine-induced enhancement of electroretinographic oscillatory potentials].

The inhibitory action of SCH 23390 (SCH, D1-antagonist) or sulpiride (SUL, D2-antagonist) on the dopamine-induced enhancement of the electroretinographic oscillatory potentials was examined in anesthetized albino rabbits. Enhancement of the oscillatory potentials by intravitreal dopamine (50 microM intravitreal concentration) injection was blocked by a simultaneous intravitreal injection of SCH (20 microM) but not by SUL (50 microM, 100 microM). These results suggest that D1-receptor is mainly responsible for the dopamine-induced enhancement of the oscillatory potentials.

Action Potentials

Development of electroretinographic alterations in streptozotocin-induced diabetes in rats.

Development of electroretinographic alterations in 9-week-old experimental diabetic rats was studied for up to 6 weeks after a single intraperitoneal injection of streptozotocin (STZ, 60 mg/kg). The amplitudes and the peak latencies of the a and b waves in the diabetic rats did not differ significantly from those in the control rats. In contrast, the diabetic rats showed a significantly smaller amplitude of the second oscillatory potential (OP) 6 weeks after STZ treatment, and furthermore significantly delayed OP peaks as early as 2-3 weeks after STZ treatment. Vitreous fluorophotometric abnormality developed 6 weeks after STZ treatment. None of the diabetic rats had fundus angiographic changes. These results suggest that hyperglycemia or its related changes rapidly affects the light-induced electrical activities of the retina.

Animals

Non-toxic concentrations of cephem antibiotics for intravitreal application--evaluation by in vitro electroretinogram.

Non-toxic concentrations of ceftazidime (CAZ), cefuzonam sodium (CZON) and cefmetazole sodium (CMZ) for intravitreal use were assessed by the electroretinogram in in vitro perfused eyecups of albino rabbits. None of the a-wave, the b-wave and the oscillatory potentials deteriorated with 300 microM CAZ, 300 microM CZON or 500 microM CMZ. The oscillatory potentials were delayed and/or diminished at the concentration which did not change the a- and b-waves (500 microM and 1.0 mM for CAZ and CZON, 1.0 mM for CMZ). Thus, the oscillatory potentials were more vulnerable to these chemicals than the a- and b-waves. Not only the classical a- and b-waves, but also the oscillatory potentials should be examined in retinal toxicology studies by the electroretinogram.

Animals

[Alteration of frog in vitro electroretinographic c-wave in modified extracellular cation concentration].

Effects of extracellular cation (Ca2+, Mg2+, Na+) concentrations on the electroretinographic c-wave were studied in the isolated neural retina-retinal pigment epithelium-choroid tissue of the bullfrog. Among the conditions studied (Ca2+, 0.5-5.0 mM: Mg2+, 0.5-5.0 mM: Na2+, 89.0-109.0 mM), only Ca2+ concentration significantly affected the c-wave. Between 1.0 mM and 5.0 mM Ca2+, the amplitude and the rise time (interval from the light onset to 90% amplitude) of the c-wave were positively and reversely correlated to Ca2+ concentration, respectively. The present results suggest that Ca2+ is one of the major determinants in the extracellular milieu on the c-wave, which is presumably due to its effects on the photoreceptoral activities.

Animals

Open heart surgery under total extracorporeal circulation in a patient with advanced glaucoma.

A patient with Wolff-Parkinson-White syndrome and severe glaucoma underwent division of the accessory pathway under total extracorporeal circulation (ECC). During ECC, systolic systemic pressure was maintained at 60-80 mmHg. Arterial pressure in the optic nerve terminal is reported to be half to one-third of systemic arterial pressure and approximates 20 mmHg during ECC. In the case presented, intraocular pressure was maintained below 15 mmHg throughout ECC. Postoperative examination of the patient revealed no change in visual acuity. During ECC, intraocular pressure may exceed the ocular bottom pressure, placing the optic nerve at risk of ischaemia. In cases where optic nerve ischaemia from ECC is likely, preoperative examination by an ophthalmologist is needed.

Adult

Evaluation of retinal integrity in eyes with retained intraocular metallic foreign body by ERG and EOG.

In three eyes with a retained intraocular metallic foreign body, the neural retina and retinal pigment epithelial (RPE) integrity were evaluated by means of ERG (a-wave, b-wave, oscillatory potentials) and non-photic EOG responses from the RPE (hyperosmolarity response, Diamox response, bicarbonate response). All three cases were judged in an early stage of retinal impairment on the basis of a well-preserved or supernormal b-wave amplitude and showed good postoperative prognosis. Out of three non-photic responses from the RPE, only the bicarbonate response was preoperatively reduced in two out of the three eyes.

Adult

[Effects of extracellular K+ concentration on the ERG c-wave].

The effects of K+ concentration in the perfusate on ERG were examined in bullfrog neural retina-retinal pigment epithelium-choroid preparations. In the range of K+ concentration between 1.0 and 6.0 mM, an increase in K+ concentration caused a decline in the b-wave amplitude, while leaving the b-wave peak latency almost unchanged. An increase in K+ concentration in the range between 1.0 and 3.0 mM enhanced the c-wave amplitude, while an increase in K+ concentration in the range between 4.0 and 6.0 mM diminished it. An increase in K+ concentration tended to shorten the time course of the c-wave. These results suggest that variations in the K+ concentration in tissue fluid may partially account for the marked inter- and intra-individual variations of the c-wave.

Animals

Electroretinographical changes due to antimicrobials.

We evaluated the retinal toxicity of antimicrobials (sulbenicillin, cefazolin, flomoxef, gentamicin, sisomicin, netilmicin, tobramycin, amikacin, vancomycin, ofloxacin, lomefloxacin, and miconazole) by the electroretinogram, before and after a single-shot intravitreal injection in rabbits. The clinical dosage for single-shot intravitreal injections which we recommend are 2 mg for sulbenicillin, 0.25 mg for cefazolin, 0.2 to 0.4 mg for flomoxef, 0.1 mg for gentamicin, 0.1 to 0.2 mg for netilmicin, 0.2 to 0.4 mg for amikacin, 0.2 mg for tobramycin, 1 mg for vancomycin, 0.2 mg for ofloxacin, 0.2 mg for lomefloxacin, and 0.05 mg for miconazole.

4-Quinolones

[Effects of aminoglycosides on the rabbit in-vivo ERG].

We evaluated the retinal toxicity of aminoglycosides (gentamicin, sisomicin, netilmicin, tobramycin and amikacin) by ERG, before and after a single-shot intravitreal injection in rabbits. Gentamicin 200 micrograms abolished the c-wave one week after injection, only slightly diminishing the b-wave and the oscillatory potentials (OPs). Gentamicin 80 micrograms did not alter the ERG up to at least 8 weeks after injection. All the ERG components examined were abolished by 200 micrograms and were irreversibly suppressed by 80 micrograms of sisomicin for the entire period of follow-up. Netilmicin (200 micrograms) or tobramycin (200 micrograms) transiently suppressed the b-wave, c-wave and the OPs. Amikacin (200 micrograms) caused no ERG changes for at least 8 weeks after injection. The clinical doses for single-shot intravitreal injections that we recommend are 100 micrograms for gentamicin, 200 micrograms for netilmicin, 200 micrograms for tobramycin and 200-400 micrograms for amikacin.

Aminoglycosides

[Effects of vancomycin and ofloxacin on rabbit ERG in vivo].

The retinal toxicity of vancomycin and ofloxacin was studied by electroretinogram (ERG) before and after intravitreal injection in rabbits. Vancomycin is known to be effective on methicillin-resistant Staphylococcus aureus. A dose of 1mg vancomycin caused no ERG change for at least eight weeks after injection. The feature that ERG became non-recordable during one to four weeks after an intravitreal injection of 10mg vancomycin, with recovery of only the c-wave was conspicuous. A dose of 200 micrograms ofloxacin did not cause deterioration of the b-wave, the c-wave or the oscillatory potentials throughout the follow-up period up to eight weeks. Judging from the susceptibility of each ERG component to antimicrobials and taking into account the difference of vitreous volume between rabbits and humans, clinical doses of intravitreal single-shot injection should be less than 1mg for vancomycin and 200 micrograms for ofloxacin.

Animals

Retinal toxicity of antibiotics: evaluation by electroretinogram.

Toxicity of an intravitreal injection of gentamicin sulfate, disodium sulbenicillin and cefazolin sodium on the retina was investigated by electroretinogram in albino and pigmented rabbits. Recordings were made before injection and 2 hours and 3, 7, 14, and 21 days after injection. Significant differences were found in the susceptibility of the electroretinogram components to various antibiotics as follows. Gentamicin 0.24 mg/0.1 ml irreversibly abolished all the components examined. Sulbenicillin 4.0, 8.0, or 12 mg/0.1 ml transiently suppressed the b-wave and the oscillatory potentials incrementally with increasing dose. Cefazolin 0.5, 2.0, or 5.0 mg/0.1 ml selectively reduced the oscillatory potentials, leaving the a- and b-waves almost unattenuated. The cefazolin-suppressed oscillatory potentials recovered within 14 days after injection. Judging from the most susceptible electroretinogram components to each antibiotic, we recommend intravitreal doses of these antibiotics for clinical use as follows: gentamicin 0.1 mg/0.1 ml, sulbenicillin 2 mg/0.1 ml, and cefazolin 0.25 mg/0.1 ml.

Animals