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1.
J Cataract Refract Surg ; 27(9): 1386-91, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11566520

ABSTRACT

PURPOSE: To prospectively evaluate the usefulness of a subconjunctival steroid injection given at the completion of cataract surgery in patients with diabetes mellitus. SETTING: University of Tokyo School of Medicine, Tokyo, Kaiya Eye Clinic, Hamamatsu, and Jyosai Hospital, Tokyo, Japan. METHODS: One hundred four eyes of 104 diabetic patients having routine small incision cataract surgery were randomized into 2 groups. One group received a subconjunctival injection of dexamethasone and the other group did not. Aqueous flare intensity was measured with the laser flare meter preoperatively and 1, 2, 5, 7, and 14 days postoperatively. Another 19 diabetic patients having routine cataract surgery were randomized to receive a subconjunctival steroid injection or not; blood glucose concentration was measured 4 times a day for 3 days postoperatively. RESULTS: There was no significant difference between the 2 groups in aqueous flare values at any postoperative time. The subconjunctival steroid injection induced a transient but significant increase in blood glucose on the day of surgery. CONCLUSION: A subconjunctival steroid injection given at the completion of cataract surgery in diabetic patients had no beneficial effects.


Subject(s)
Blood Glucose/metabolism , Conjunctiva/drug effects , Dexamethasone/administration & dosage , Diabetes Mellitus/metabolism , Glucocorticoids/administration & dosage , Postoperative Complications/metabolism , Uveitis, Anterior/metabolism , Aged , Aqueous Humor/metabolism , Diabetes Complications , Diabetic Retinopathy/etiology , Diabetic Retinopathy/metabolism , Female , Humans , Injections , Lens Implantation, Intraocular , Male , Phacoemulsification , Prospective Studies
2.
Am J Ophthalmol ; 132(1): 108-9, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11438064

ABSTRACT

PURPOSE: To assess the contraction of continuous curvilinear capsulorhexis after cataract surgery in eyes with past pars plana vitrectomy. METHODS: In a prospective study, 16 eyes of 16 patients underwent phacoemulsification and implantation of a foldable acrylic intraocular lens after pars plana vitrectomy. Eyes after intensive or repeated vitrectomy were not included. Twenty eyes of 19 patients served as age-matched controls. Aqueous flare intensity was measured using the laser flare-cell meter 1 year after surgery. The area of anterior capsular opening (ACO) was determined by diaphanoscopy using the anterior eye segment analysis system EAS-1000 at 1 day and 1 year postoperatively. RESULTS: There was no significant difference in the mean ACO area between the vitrectomy and control groups both at 1 day and 1 year postoperatively. Aqueous flare intensity 1 year after surgery was slightly higher in the vitrectomy group, but the difference was not statistically significant. CONCLUSION: Eyes after simple vitrectomy are not at a higher risk of ACO contraction following cataract surgery.


Subject(s)
Contracture/etiology , Lens Capsule, Crystalline/pathology , Phacoemulsification/adverse effects , Vitrectomy , Aged , Aqueous Humor/immunology , Capsulorhexis , Humans , Lens Implantation, Intraocular , Prospective Studies , Risk Factors , Uveitis, Anterior/etiology
3.
Arch Histol Cytol ; 64(1): 69-79, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11310507

ABSTRACT

Retinal projections to the nucleus of the optic tract (NOT) and accessory optic nuclei (AON) were studied in the postnatal hooded rat after monocular injection of cholera toxin B subunit (CTB) into the vitreous chamber of the eye. At all postnatal ages, retinal axons were labeled sensitively; they revealed dense projections to the contralateral, and sparse but distinct projections to the ipsilateral, NOT and AON. The CTB labeling enabled the first delineation of the complete morphology of developing retinal axons in the ipsilateral NOT and AON. From postnatal day (P) 1 to P3, axons with complex growth cones were seen, and unbranched collaterals with simple growth cones increased and extended gradually. At P6, complex growth cones disappeared while branched collaterals with simple growth cones as well as small-sized varicosities increased. By P12 (two days before eye-opening) the adult-like pattern of terminal arbors appeared. The branched collaterals with tiny, small-sized varicosities present probably represented developing synaptic boutons. At P16 (after eye opening), the pattern of terminal arbors was well developed, almost to the same extent as in the adult. By contrast, a broadly distributed, transient retinal projection around NOT and AON was gradually eliminated; it started to disappear during the first few postnatal days, and was fully retracted by the time of eye-opening time to a pattern normal for the adult.


Subject(s)
Animals, Newborn/anatomy & histology , Eye/growth & development , Geniculate Bodies/growth & development , Retina/growth & development , Visual Pathways/growth & development , Animals , Animals, Newborn/growth & development , Brain Stem/cytology , Brain Stem/growth & development , Brain Stem/metabolism , Cholera Toxin/administration & dosage , Cholera Toxin/metabolism , Eye/cytology , Eye/metabolism , Immunohistochemistry , Rats , Rats, Long-Evans , Retina/anatomy & histology , Retina/metabolism , Retinal Ganglion Cells/cytology , Retinal Ganglion Cells/metabolism , Time Factors , Visual Pathways/cytology , Visual Pathways/metabolism
4.
Am J Ophthalmol ; 131(3): 301-4, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11239860

ABSTRACT

PURPOSE: To assess quantitatively the cumulative effect of hyperglycemia on lens transparency in patients with juvenile type 1 diabetes mellitus. METHODS: Subjects were 30 patients (30 eyes) with type 1 diabetes mellitus who had well-documented records on the duration of diabetes mellitus and condition of glycemic control from the onset. They were 35 years of age or younger (mean, 26.0 years), had a history of type 1 diabetes mellitus at least 5 years (mean, 8.4 years), had corrected visual acuity of 20/20 or better, and showed no clinically apparent cataract on slit-lamp examination. Twenty-one eyes of 21 subjects served as age-matched normal controls. They were 35 years of age or younger (mean, 25.7 years), had no diabetes mellitus, had corrected visual acuity of 20/20 or better, and showed no signs of cataract on slit-lamp examination. The degree of lens opacity was quantified using the anterior eye segment analysis system based on the Scheimpflug principle. An index was created to represent the cumulative effect of long-term glycemic control (hyperglycemic accumulation) by multiplying the average hemoglobin A(1c) value and the number of months from the onset. RESULTS: The patients with diabetes mellitus exhibited significantly greater degree of lens opacity than the normal controls (P =.017, Mann-Whitney U-test). Among the patients with diabetes mellitus, the lens opacity was greater in eyes with retinopathy than those without retinopathy (P =.011). Multiple regression analysis revealed that only the index of hyperglycemic accumulation significantly correlated with the degree of lens opacity (P =.042). CONCLUSION: Accumulated effect of hyperglycemia is related to the lens transparency in patients with diabetes.


Subject(s)
Blood Glucose/physiology , Cataract/physiopathology , Diabetes Mellitus, Type 1/physiopathology , Hyperglycemia/physiopathology , Lens, Crystalline/physiopathology , Adult , Diabetic Retinopathy/physiopathology , Female , Humans , Male , Visual Acuity
5.
Br J Ophthalmol ; 85(1): 21-3, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11133706

ABSTRACT

AIM: To investigate change in the area of anterior capsular opening (ACO) after cataract surgery and its relation to the degree of postoperative anterior inflammation in patients with diabetes mellitus (DM). METHODS: 31 eyes of 31 patients with DM and 30 eyes of 30 normal controls scheduled to undergo cataract surgery were examined prospectively. The area of ACO was measured with an anterior eye segment analysis system (EAS-1000) on the day following surgery and 3, 6, and 12 months after surgery. Comparative analyses were made on the area of ACO relative to the presence of DM and diabetic retinopathy (DR). The percentage reduction of area of ACO was calculated from values 1 day and 12 months after surgery, and multiple regression analysis was performed on the presence of DM, patient age, ACO area on the first postoperative day, and aqueous flare intensity 1 day and 12 months after surgery. RESULTS: The area was significantly smaller in the DM group at 3 (p=0.015, Student's t test), 6 (p=0.011), and 12 (p=0.010) months postoperatively. Patients having DR showed significantly smaller ACO area than the non-DR group 3 (p=0.039), 6 (p=0.033), and 12 (p=0.028) months after surgery. Multiple regression analysis revealed that presence of DM (p=0.003) and aqueous flare intensity 12 months after surgery (p=0.039) significantly correlated with the percentage reduction of area of ACO. Age, ACO area at 1 day postoperatively, and aqueous flare intensity immediately after surgery were not relevant to ACO contraction. CONCLUSIONS: Anterior capsular contraction after cataract surgery was greater in eyes of DM patients, especially in those with DR and increased permeability of the blood-aqueous barrier.


Subject(s)
Diabetes Mellitus/pathology , Lens Capsule, Crystalline/pathology , Phacoemulsification , Aged , Aqueous Humor , Diabetic Retinopathy/pathology , Endophthalmitis/pathology , Follow-Up Studies , Humans , Middle Aged , Postoperative Complications/pathology , Postoperative Period , Prospective Studies , Regression Analysis
6.
Chem Res Toxicol ; 13(10): 993-1001, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11080048

ABSTRACT

When arylaminating carcinogens are administered to cells, they mainly generate the C8-arylamino-2'-deoxyguanosine adduct in DNA. A mechanism for this was proposed in which N7-arylaminated 2'-deoxyguanosine acts as an intermediate; however, it remained unclear whether this is actually the case. To elucidate the mechanisms involved in the generation of this adduct, a series of 5-substituted 1-methylbenzimidazole derivatives were used as models of the imidazole moiety of 2'-deoxyguanosine. Syntheses of a series of 5-substituted (CH(3), H, F, CF(3), or NO(2)) 1-methyl-3-phenylaminobenzimidazolium salts (7) and their related compounds were carried out, and the chemical characteristics of these products were examined. Heating compound 7 at 80 degrees C for 48 h in H(2)O/MeOH provided 5-substituted 1-methyl-2-oxo-2, 3-dihydrobenzimidazoles but only when this compound contained a CF(3) or NO(2) substituent. Compound 7 decomposed in alkaline media, and its rate of decomposition increased when this compound had a stronger electron-withdrawing substituent. The product obtained under these conditions was 4-substituted N(1)-methyl-2-phenylazoaniline. On the other hand, when 1-methyl-3-(4-nitrophenylamino)benzimidazolium salt was treated under the same conditions as described above, it generated a demethylated product, 1-(4-nitrophenylamino)benzimidazole, when heated in H(2)O/MeOH and N(1)-formyl-N(1)-methyl-2-phenylazoaniline when treated in alkaline media. When the chemical characteristics of 3-phenylamino and 3-amino groups were compared using 3-substituted 1-methyl-5-(trifluoromethyl)benzimidazoles, the 3-phenylamino derivative was found to be more reactive.


Subject(s)
Amines/chemistry , Benzimidazoles/chemistry , DNA Adducts/chemistry , Deoxyguanosine/chemistry , Amines/chemical synthesis , Benzimidazoles/chemical synthesis , DNA Adducts/chemical synthesis , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/chemical synthesis , Hot Temperature , Hydrogen-Ion Concentration , Magnetic Resonance Spectroscopy , Models, Chemical
7.
Am J Ophthalmol ; 130(3): 354-5, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11020417

ABSTRACT

PURPOSE: To report the influence of rapid glycemic control on lens opacity in patients with diabetes mellitus. METHODS: In a prospective study, nine patients with adult onset diabetes mellitus and glycosylated hemoglobin values over 9% were divided into two groups, rapid glycemic control and slow glycemic control groups, based on the time course of glycosylated hemoglobin values after the initiation of glycemic control. The lens thickness and opacity were measured using the anterior eye segment analysis system. RESULTS: One week after onset of treatment, the lens in rapid glycemic control group became significantly thicker than in pretreatment, but returned to the baseline level at the subsequent measurement points. The lens opacity index in the rapid glycemic control group increased significantly (P <.01, paired t test) 4 months after the glycemic control, which persisted throughout the 1-year study period. The lens thickness and opacity in the slow glycemic control group did not change significantly. CONCLUSION: It was suggested that rapid glycemic control can induce an irreversible increase in lens opacification.


Subject(s)
Cataract/prevention & control , Diabetes Mellitus, Type 2/therapy , Hyperglycemia/therapy , Lens, Crystalline/physiopathology , Adult , Blood Glucose/analysis , Cataract/physiopathology , Diabetes Mellitus, Type 2/physiopathology , Glycated Hemoglobin/metabolism , Humans , Hyperglycemia/physiopathology , Prospective Studies , Visual Acuity
8.
Bioorg Med Chem ; 8(1): 37-42, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10968262

ABSTRACT

Reactions of a series of 1-aminobenzimidazoles and 1-amino-3-methylbenzimidazolium chlorides with 2,4-pentanedione were carried out and pyridazino[1,6-a]benzimidazoles and 2-pyrazolylanilines were generated. The product ratios of these compounds remarkably depended on the reaction conditions and on the electronic character of the substituent at the benzene moiety. The possible mechanisms involved in these reactions are discussed.


Subject(s)
Benzimidazoles/chemistry , Pentanones/chemistry , Chromatography, High Pressure Liquid , Magnetic Resonance Spectroscopy , Mass Spectrometry
9.
Vis Neurosci ; 17(6): 893-904, 2000.
Article in English | MEDLINE | ID: mdl-11193105

ABSTRACT

The cat's lateralis medialis-suprageniculate nuclear complex (LM-Sg) in the thalamus receives input from various brain regions such as the superior colliculus, brain stem, and spinal cord, as well as from visual association cortex. In a previous study, we demonstrated that LM-Sg receives cholinergic fibers from the pedunculopontine tegmental nucleus (PPT) and that cholinergic terminals make synaptic contacts with the dendrites of glutamatergic projection neurons and of GABAergic interneurons (Hoshino et al., 1997). In this study, we investigate the distribution and the organization of PPT terminals by means of a combined anterograde tracer (biotinylated dextran amine, BDA) and immunohistochemical methods. When stained by acetylcholinesterase (AChE), the LM-Sg is not uniformly immunoreactive, but rather is patchily labeled and shows a streaming type of reactivity. The tissue content appears high in enzyme activity in AChE-positive zones and is much lighter in activity in AChE-negative zones. We compared the synaptic organization between AChE-positive and AChE-negative portions of the LM-Sg in separate groups of electron-microscopic material: four types of vesicle containing profiles (RS, RL, F1, and PSD) as well as synaptic glomeruli were observed in this nucleus. Among these, the PSD profiles were observed more frequently in AChE-positive portions than in AChE-negative zones. Furthermore, the number of glomeruli was significantly higher in AChE-positive than in AChE-negative zones. Following the injection of BDA into PPT, labeled terminals within LM-Sg were rather more concentrated in the AChE-positive portion. Although the majority of PPT terminals made synaptic contacts with dendrites in the neuropil, a few terminals were involved in the synaptic glomeruli. The present results show that the synaptic organization is distinctly different between the AChE-positive and AChE-negative portions of LM-Sg. These results suggest that the AChE-positive portions of LM-Sg are relatively more involved in integrating information arising from a diverse set of inputs and processing that information within glomeruli in a complex manner than occurs in the AChE-negative portion of LM-Sg.


Subject(s)
Biotin/analogs & derivatives , Geniculate Bodies/physiology , Lateral Thalamic Nuclei/physiology , Nerve Endings/physiology , Synapses/physiology , Tegmentum Mesencephali/physiology , Acetylcholinesterase/metabolism , Animals , Cats , Dextrans , Female , Fluorescent Dyes , Geniculate Bodies/ultrastructure , Immunohistochemistry , Lateral Thalamic Nuclei/ultrastructure , Male , Microscopy, Electron , Nerve Endings/ultrastructure , Pons , Staining and Labeling , Synapses/ultrastructure , Tegmentum Mesencephali/ultrastructure
10.
Bioorg Med Chem Lett ; 9(7): 961-4, 1999 Apr 05.
Article in English | MEDLINE | ID: mdl-10230620

ABSTRACT

Reaction of 7-amino-9-ethylguaninium chloride with lead(IV) acetate (LTA) in MeOH yielded 8-aza-9-ethylguanine. Similarly, the reaction of 1-amino-3-methylbenzimidazolium chloride or its substituted derivatives (6-methyl, 5,6-dimethyl and 5-nitro) with LTA gave the corresponding 1-methyl-1H-benzotriazole (or 1-methyl-2-azabenzimidazole) derivatives along with N-methylformananilide derivatives.


Subject(s)
Benzimidazoles/chemistry , Guanine/analogs & derivatives , Organometallic Compounds/chemistry , Triazoles/chemical synthesis , Guanine/chemical synthesis , Guanine/chemistry , Magnetic Resonance Spectroscopy
11.
Curr Eye Res ; 18(2): 143-9, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10223659

ABSTRACT

PURPOSE: To examine the three-dimensional organization of collagen fibrils in the lamina cribrosa of normal monkey eyes and monkey eyes with laser-induced glaucoma. METHODS: Intraocular pressure elevation and glaucomatous optic discs were obtained in one eye of three adult monkeys by repeated applications of argon laser to the chamber angle. The monkey eyes were enucleated, and the collagen fibrillar network was investigated by scanning electron microscopy after cell maceration with 10% sodium hydroxide and conductive staining. RESULTS: In normal monkey eyes, round to oval shaped regular laminar pores through which axon bundles exited were observed in the lamina cribrosa. The straight, column-like pores or openings were formed by multilayered laminar plates that aligned vertically in parallel with the optic nerves. The surface of the laminar plates was covered by delicate, loosely arranged collagen fibrils. The inner surface of the pores was smooth, made up of well-packed collagen fibers. In glaucomatous eyes, the laminar pores were clogged by tightened collagen fibrils. The inner surface of the pores was irregular, and the pores were narrowed or distorted. CONCLUSIONS: Alterations in the three-dimensional organization of collagen fibrils were demonstrated in the optic nerve head of glaucomatous monkey eyes. The architectural changes may affect the flexibility and resilience required of the lamina cribrosa in supporting optic nerve fibers.


Subject(s)
Collagen/ultrastructure , Glaucoma/pathology , Laser Therapy/adverse effects , Optic Disk/ultrastructure , Animals , Glaucoma/etiology , Intraocular Pressure , Macaca fascicularis , Microscopy, Electron, Scanning , Trabecular Meshwork/surgery
12.
Jpn J Ophthalmol ; 43(1): 20-4, 1999.
Article in English | MEDLINE | ID: mdl-10197738

ABSTRACT

PURPOSE: To quantitatively assess pupillary functions after small pupil cataract surgery using the flexible iris retractor. METHODS: Subjects were 11 patients (12 eyes) with small pupils who underwent phacoemulsification and intraocular lens implantation. Pupils were enlarged using the flexible iris retractor intraoperatively, and postoperative iriscorder data were compared with the data of 20 normal controls who underwent standard phacoemulsification and intraocular lens implantation. RESULTS: Although pupillary area before light stimulus did not differ between the groups, contraction rate after light stimulus was significantly lower in the small pupil group than in the normal controls. The velocity of contraction and dilation was also significantly slower in the small pupil group. Wider pupillary stretching during surgery resulted in deteriorated pupillary functions after surgery. Eyes of patients on long-term miotic therapy with pilocarpine showed poorer pupillary reaction postoperatively. CONCLUSION: Inappropriate use of the flexible iris retractor causes an atonic, chronically enlarged postoperative pupil. To avoid postoperative pupillary complications, miotic pupils should not be stretched to larger than a 5.0 x 5.0 mm square.


Subject(s)
Iris , Miosis/prevention & control , Phacoemulsification/instrumentation , Postoperative Complications/prevention & control , Pupil/physiology , Aged , Aged, 80 and over , Follow-Up Studies , Humans , Lens Implantation, Intraocular/instrumentation , Middle Aged , Miosis/physiopathology , Postoperative Complications/physiopathology
13.
Neurobiology (Bp) ; 7(4): 445-60, 1999.
Article in English | MEDLINE | ID: mdl-10897805

ABSTRACT

It is generally known that the nucleus of the optic tract (NOT) subserves visuomotor relations between the retina and preoculomotor structures as the only subcortical pathway mediating optokinetic responses (OKR) in mammals. We have examined the projections from the retina and visual cortical areas (areas 17, 18a and 18b) to NOT using tracers (wheat germ agglutinin-conjugated horseradish peroxidase, WGA-HRP and cholera toxin B subunit, CTB) in order to clarify how these two different functional inputs to OKR are organized. CTB injection into the vitreous body resulted in anterograde label almost exclusively in the contralateral NOT. Ultrastructually, the size of the retinal axon terminals was small (up to 0.7 micron in diameter), contained round synaptic vesicles and pale mitochondria, and made asymmetrical synaptic contacts with both GABA-positive and GABA-negative NOT neurons. Visual cortical area 17 and the transitional area between area 17 and 18a, or between area 17 and 18b projected their axons to the ipsilateral NOT. Ultrastructually, the size of the cortical axon terminals was small (up to 0.5 micron in diameter), contained round synaptic vesicles, and made asymmetrical synaptic contacts only with GABAnegative NOT neurons. With light and electron microscopical observation, there was a considerable overlap in the cortico-NOT and retino-NOT projection pattern: GABA-negative (presumably NOT projection) neurons simultaneously receive input from both cortical and retinal terminals. From these results, it seems reasonable to postulate that inputs from visual cortical areas in the pigmented rat cooperate with those from the retina in controlling OKR.


Subject(s)
Retinal Ganglion Cells/ultrastructure , Visual Cortex/cytology , Visual Pathways/cytology , Animals , Cholera Toxin , Dendrites/ultrastructure , Microscopy, Electron , Nystagmus, Optokinetic/physiology , Presynaptic Terminals/ultrastructure , Rats , Rats, Long-Evans , Retinal Ganglion Cells/chemistry , Retinal Ganglion Cells/physiology , Tissue Embedding , Visual Cortex/chemistry , Visual Cortex/physiology , Visual Pathways/physiology , Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate , gamma-Aminobutyric Acid/analysis
14.
Chem Res Toxicol ; 11(11): 1249-53, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9815183

ABSTRACT

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces parkinsonism in humans after its oxidation into 1-methyl-4-phenylpyridinium ion (MPP+) by type B monoamine oxidase. The 1-amino analogues of MPTP and MPP+, 1-amino-4-phenyl-1,2,3, 6-tetrahydropyridine (APTP) and 1-amino-4-phenylpyridinium ion (APP+), were synthesized, and their cytotoxicity to clonal pheochromocytoma PC12 cells was examined using a tetrazolium formazan assay. After incubation for 48 and 72 h, both APP+ and APTP were found to be cytotoxic to PC12 cells, whereas with the N-methyl analogues, only MPP+, but not MPTP, was cytotoxic. The cytotoxicity of APTP increased with incubation time and equaled that of MPP+ after 72 h. It was found that APTP was oxidized to APP+ by type A monoamine oxidase in PC12 cells, suggesting that APP+ itself may damage the cells. In addition to APTP and APP+, N-amino analogues of N-methylisoquinolines and related derivatives were also synthesized and examined for their cytotoxicity to PC12 cells.


Subject(s)
1-Methyl-4-phenylpyridinium/toxicity , Antineoplastic Agents/toxicity , Dopamine Agents/toxicity , MPTP Poisoning , Animals , Cell Survival , Monoamine Oxidase Inhibitors/toxicity , Oxidation-Reduction , PC12 Cells , Rats
15.
Arch Ophthalmol ; 116(1): 62-8, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9445209

ABSTRACT

OBJECTIVE: To examine the 3-dimensional collagen fibril organization in the Bowman layer of keratoconus corneas. METHODS: Eight keratoconus corneas, 8 corneas with other diseases, and 5 normal human corneas were studied. A cell maceration method in combination with scanning electron microscopy was used to examine the collagen network in the Bowman layer. RESULTS: In normal corneas, the surface of the Bowman layer was smooth and collagen fibrils were regularly arranged. By contrast, sharply edged defects in the Bowman layer were found in keratoconus corneas. Lattice-like configurations of the ruptured Bowman layer and collagenous scar tissue were observed, to varying degrees, in all keratoconus corneas examined. None of the other diseased corneas exhibited the ruptures. CONCLUSIONS: Scanning electron microscopy demonstrated alterations in the Bowman layer specific to keratoconus. Fragmentation of the Bowman layer may be an early change leading to keratoconus conditions.


Subject(s)
Cornea/ultrastructure , Keratoconus/pathology , Microscopy, Electron, Scanning , Adolescent , Adult , Aged , Basement Membrane/ultrastructure , Cell Division , Child, Preschool , Collagen/ultrastructure , Corneal Diseases/pathology , Female , Humans , Male , Middle Aged , Rupture, Spontaneous
16.
Bioorg Med Chem Lett ; 8(6): 625-30, 1998 Mar 17.
Article in English | MEDLINE | ID: mdl-9871572

ABSTRACT

Oxidation of seven 1-methylbenzimidazole (MBI) derivatives (with pKa's ranging from 1.6 to 6.0) was carried out with m-chloroperoxybenzoic acid and structures of the products formed were identified. (Condensed benzene moiety-hydroxylated)-2-(m-chlorobenzyloxy)-MBIs and 2-oxo-MBIs were obtained from MBIs with pKa's of more than 5.6 and about 3.3, respectively.


Subject(s)
Benzimidazoles/metabolism , Chlorobenzoates/metabolism , Indicators and Reagents/metabolism , Methylation , Models, Chemical
17.
Bioorg Med Chem Lett ; 8(16): 2197-202, 1998 Aug 18.
Article in English | MEDLINE | ID: mdl-9873512

ABSTRACT

Reactions of 7-aminoadenines with 2,4-pentanedione yielded pyridazino[6,1-f]purines and 5-pyrazolylpyrimidines. The structure of the latter was identified by X-ray analysis. Reaction of 9-amino-N6-methyladenine with 2,4-pentanedione gave pyridazino[1,6-e]purine and Schiff base products. Possible reaction mechanisms are discussed.


Subject(s)
Pentanones/chemistry , Purines/chemical synthesis , Crystallography, X-Ray , Indicators and Reagents , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Conformation , Molecular Structure , Purines/chemistry
18.
J Neural Transm (Vienna) ; 105(10-12): 1253-64, 1998.
Article in English | MEDLINE | ID: mdl-9928894

ABSTRACT

A 1-amino analog of MPTP, 1(N)-amino-4-phenyl-1,2,3,6-tetrahydropyridine, was synthesized and the oxidation was examined using human synaptosomal mitochondria as sources of type A and B monoamine oxidase. An oxidation product, 1-amino-4-phenylpyridinium ion, was quantified by high-performance liquid chromatography-fluorometric detection. The amino analog was a substrate of both type A and B monoamine oxidase and the oxidation depended linearly on the enzyme amount and the reaction time with an optimal pH around 7.5. After the systemic injection of the amino analog in C57/black mice for one week, 1-amino-4-phenylpyridinium ion was detected in the brain. 1(N)-Amino-4-phenyl-1,2,3,6-tetrahydropyridine was proved to be cytotoxic to pheochromocytoma PC12 cells, and it may be a new neurotoxin bioactivated through the oxidation by type A and B monoamine oxidase.


Subject(s)
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/analogs & derivatives , Monoamine Oxidase/metabolism , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/metabolism , Animals , Humans , Male , Mice , Mice, Inbred C57BL , Mitochondria/drug effects , Mitochondria/enzymology , Mitochondria/metabolism , Monoamine Oxidase Inhibitors/pharmacology , Oxidation-Reduction , PC12 Cells , Rats , Synaptosomes/drug effects , Synaptosomes/enzymology , Synaptosomes/metabolism
19.
Chem Pharm Bull (Tokyo) ; 45(10): 1665-70, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9353895

ABSTRACT

Several triterpenes were tested for cytotoxicity by our contrived primary screening method using resting or dormant leukemia L1210 cells after 3 d-preculture without medium change. Some triterpenes were found to be more cytotoxic toward the 3 d-precultured resting cells than toward the growing cells in a fresh medium. These triterpenes are distinguished by highly selective cytotoxicity toward the starved resting cells unlike common anticancer agents. The highest selectivity was shown by betulinic acid, the ratio of its IC50 values toward the growing versus resting cells amounting to 175. It is suggested that this selective cytotoxicity is attributable to low pH (< or = 6.8) of the medium. It is noteworthy that betulinic acid is not cytotoxic at all in media of ordinary pH (> or = 7.0) even after a 48-h exposure. Betulinic acid might be promising as an antitumor agent toward solid tumors because the interior pH of tumor tissues is generally lower than in normal tissues.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , DNA Damage/drug effects , Leukemia L1210/pathology , Triterpenes/pharmacology , Animals , Cell Count , Cell Survival , Dose-Response Relationship, Drug , Hydrogen-Ion Concentration , Pentacyclic Triterpenes , Structure-Activity Relationship , Tumor Cells, Cultured/drug effects , Betulinic Acid
20.
J Chromatogr B Biomed Sci Appl ; 702(1-2): 245-8, 1997 Nov 21.
Article in English | MEDLINE | ID: mdl-9449579

ABSTRACT

A new preparation method was devised using beta-cyclodextrin as a mobile-phase additive in a reversed-phase high-performance liquid chromatography system. Preparative separation of the biologically active (R)-enantiomer was achieved from racemic N-methylsalsolinol. Beta-cyclodextrin was removed completely in good yield by acid extraction and solid-phase extraction. By a slight modification, this method will be applicable to the isolation of various types of biologically important enantiomers.


Subject(s)
Chromatography, High Pressure Liquid/methods , Cyclodextrins/chemistry , Salsoline Alkaloids/isolation & purification , Tetrahydroisoquinolines , Circular Dichroism , Salsoline Alkaloids/chemistry , Spectrophotometry, Ultraviolet , Stereoisomerism
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