Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022568 (keratitis)
 5,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acanthamoeba species can cause granulomatous encephalitis and keratitis in man. The mechanisms that underlie tissue damage and invasion by the amoebae are poorly understood, but involvement of as yet uncharacterized proteinases has been suggested. Here, we employed gelatin-containing gels and azocasein assays to examine proteinase activities in cell lysates and in medium conditioned by Acanthamoeba polyphaga trophozoites. Azocasein hydrolysis by cell lysates was optimally detected at pH 4.0-5.0 and was predominantly associated with the activity of cysteine proteinases. Compatible with enzyme activation during secretion, culture supernatants additionally contained a prominent azocasein hydrolyzing activity attributable to serine proteinases; these enzymes were better detected at pH 6.0 and above, and resolved at 47, 60, 75, 100, and >110 kDa in overlay gelatin gels. Although a similar banding profile was observed in gels of trophozoite lysates, intracellular serine proteinases were shown to be activated during electrophoresis and to split the substrate during migration in sodium dodecyl sulfate gels. Blockage of serine proteinases with phenylmethylsulfonylfluoride prior to electrophoresis permitted the detection of 43-, 59-, 70-, and 100-130-kDa acidic cysteine proteinases in cell lysates, and of 3 (43, 70, and 130 kDa) apparently equivalent enzymes in culture supernatants. Under the conditions employed, no band associated with a metalloproteinase activity could be depicted in substrate gels, although the discrete inhibition of supernatants' azocaseinolytic activity by 1,10-phenanthroline suggested secretion of some metalloproteinase.
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PMID:Proteinase activities in total extracts and in medium conditioned by Acanthamoeba polyphaga trophozoites. 1078 May 36

Sub-microlitre volumes of normal koala, mouse, dog, rat and cat tears were fractionated using size exclusion-high performance liquid chromatography (SE - HPLC), giving reproducible profiles which were different for each species. Microlitre volumes of tears were also fractionated using sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS - PAGE), resulting in good separation of individual tear proteins with a species specific distribution. Tears from koalas with conjunctivitis and mice with keratitis were similarly examined and showed mostly quantitative changes. These simple, rapid techniques gave reproducible results and, in contrast to conventional separation techniques, used easily obtainable volumes (as little as 0.75 microl) of tears. Their expansion could allow isola tion, identification and quantitation of individual tear components, enabling effective investigation of changes occurring in disease.
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PMID:Protein microanalysis of animal tears. 1087 64

The pathogenicity of Acanthamoeba isolates from keratitis patients (the Hamburg isolate from Germany, H-1 and a Philippine isolate, IB-1-7) as well as an environmental isolate, W4 was assayed in vitro using rat glial C6 cell line. Results indicate that both live amebae and cell-free supenatants from H-1 and IB-1-7 clones produced cytopathic effects (CPE) on rat glial C6 cells in a dose-and-time-dependent fashion. A dose of 10(5) cells/ml induced death and moderate areas of destruction of individual cells after 48 hours of incubation. Results of both free zone capillary electrophoresis and sodium dodecyl sulphate polyacrylamide gel electrophoresis suggest the release of amebic products to the culture medium that could at least partially explain the observed cytopathogenicity after 48 hours. Furthermore, results of SDS-PAGE indicate differences between the secretions of the isolates, with bands produced by the two ocular isolates that were not seen with the environmental isolates. That the secretions can produce a cytopathic effect (CPE) has been shown by the cytotoxicity assays using protein concentrations of the secretory products. Protein concentration of 0.30 microg/microl of culture supenatants from H-1 and IB-1-7 clones produced similar effects on the cell monolayers after 2 hours of incubation. This concentration caused the highest % cell death as measured by both trypan blue exclusion (TBE) and 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl-tetrazolium bromide (MTT) assays. In contrast, using W4 clone, corresponding concentrations of both trophozoites and culture supernatant did not cause significant cell death and cellular disintegration.
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PMID:Cytopathogenicity of Acanthamoeba isolates on rat glial C6 cell line. 1092 58

Sodium borocaptate (BSH) and boronophenylalanine (BPA) are two drugs that have been used clinically for boron neutron capture therapy (BNCT) of brain tumors. We previously have reported that hyperosmotic mannitol-induced disruption of the blood-brain barrier (BBB-D), followed by intracarotid (i.c.) administration of BPA or BSH, either individually or in combination, significantly enhanced tumor boron delivery and the efficacy of BNCT in F98 glioma bearing rats. The purpose of the present study was to determine the short-term neuropathologic consequences of this treatment and the long-term effects on motor and cognitive function, as well as the neuropathologic sequelae 1 year following neutron capture irradiation. BBB-D was carried out in non-tumor bearing Fischer rats by infusing a 25% solution of mannitol i.c. followed by i.c. injection of BPA or BSH, either individually or in combination, immediately thereafter. Animals were euthanized 2 days after compound administration, and their brains were processed for neuropathologic examination, which revealed sporadic, mild, focal neuronal degeneration, hemorrhage, and necrosis. To assess the long-term effects of such treatment followed by neutron capture irradiation, non-tumor bearing rats were subjected to BBB-D after which they were injected i.c. with BPA (25 mg B/kg body weight (b.w)) or BSH (30 mg B/kg b.w.) either individually or in combination (BPA 12.5 mg and BSH 14 mg B/kg b.w.). Two and a half hours later they were irradiated at the Medical Research Reactor, Brookhaven National Laboratory, Upton, NY, with the same physical radiation doses (5.79, 8.10 or 10.06 Gy), delivered to the brain, as those that previously had been used for our therapy experiments. The animals tolerated this procedure well, after which they were returned to Columbus, Ohio where their clinical status was monitored weekly. After 1 year, motor function was assessed using a sensitive and reliable locomotor rating scale for open field testing in rats and cognitive function was evaluated by their performance in the Morris water maze, the results of which were similar to those obtained with age matched controls. After functional evaluation, the rats were euthanized, their brains were removed, and then processed for neuropathologic examination. Subtle histopathologic changes were seen in the choroid plexuses of irradiated animals that had received BPA, BSH or saline. Radiation related ocular changes consisting of keratitis, blepharitis, conjunctivitis and cataract formation were seen with similar frequency in most rats in each treatment group. Based on these observations, and the previously reported significant therapeutic gain associated with BBB-D and i.c. injection of BSH and BPA, the present observations establish its safety in rats and suggest that further studies in large animals and humans are warranted.
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PMID:Boron neutron capture therapy of brain tumors: functional and neuropathologic effects of blood-brain barrier disruption and intracarotid injection of sodium borocaptate and boronophenylalanine. 1110 Aug 16

Scleral implants of indomethacin with sodium alginate as carrier were fabricated and evaluated for various physico-chemical properties such as uniformity of thickness, weight, drug content, surface pH, percent dissolution and water up-take capacity (swelling index). The effect of drug particle size, polymer concentration, drug loading, plasticizer concentration, and effects of physical reinforcement (freeze-thawing for 3 and 6 cycles) and chemical cross-linking with calcium chloride, on the in vitro drug release characteristics were evaluated. Selected batches of the implants were subjected to pharmacodynamic studies, after scleral placement, in uveitis induced (intravitreal injection of Bovine Serum Albumin (BSA)-50 micrograms/ml) rabbit eyes. The release of indomethacin from the prepared implants followed predominantly matrix diffusion kinetics. Swelling and moisture absorption/loss studies correlated well with the in vitro release studies. The pharmacodynamic studies showed a marked improvement in the various clinical parameters (congestion, keratitis, flare, clot, aqueous cells and synechias), in the implanted eye when compared to the control eye in the rabbits.
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PMID:In vitro and in vivo characterization of scleral implants of indomethacin. 1168 26

Film-type scleral implants of indomethacin using sodium alginate and PEG 400 and 600 (3, 5, 8, and 10% w/w w.r.t. sodium alginate) as plasticizers were fabricated by solvent casting. The prepared implants were cross-linked by treatment with calcium chloride 10, 20, and 30% w/v solution, for periods between 1 to 24 hr. Uniformity of thickness, weight, and drug content and surface pH of the implants were evaluated. The influence of plasticizer type/concentration and crosslinking time/concentration of calcium chloride on indomethacin release was studied on a static dissolution setup developed by us. Selected batches of the implants were subjected to pharmacodynamic studies, after scleral placement, in uveitis-induced (intravitreal injection of bovine serum albumin 50 microg/ml) rabbit eyes. The release of indomethacin from the implants was influenced by the concentration and nature of plasticizers used. Chemical cross-linking with calcium chloride was successful in retarding the drug release. The pharmacodynamic studies showed a marked improvement in the various clinical parameters (congestion, keratitis, flare, clot, aqueous cells, and synechias) in the implanted eye when compared with the control eye in the rabbits. The implants survived for 2 weeks in vivo.
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PMID:In vitro and in vivo characterization of scleral implant of indomethacin: role of plasticizer and cross-linking time. 1461 43

Air bags, fitted in the majority of new automobiles, are safety devices activated when a sudden deceleration causes the ignition of a propellant cartridge containing sodium azide. The bag is inflated by nitrogen liberated during the combustion. Deployment releases various high-temperature gases, including nitrogen and carbon dioxide, and produces sodium hydroxide, a highly irritant alkaline substance. In about 7%-8% of cases, air bags cause dermatologic injuries such as traumatic lesions, irritant dermatitis, and chemical and thermal burns. Nondermatologic lesions, such as ocular damage (alkali keratitis, corneal abrasions), ear lesions, bone fractures, and contusive damage can also be caused by air bag deployment.
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PMID:Air bags and the skin. 1536 61

Treatments used for several neurological conditions may adversely affect the eye. Vigabatrin-related retinal toxicity leads to a visual field defect. Optic neuropathy may result from ethambutol and isoniazid, and from radiation therapy. Posterior subcapsular cataract is associated with systemic corticosteroids. Transient refractive error changes may follow treatment with acetazolamide or topiramate, and corneal deposits and keratitis with amandatine. Intraocular pressure can be elevated in susceptible individuals by anticholinergic drugs, including oxybutynin, tolterodine, benzhexol, propantheline, atropine and amitriptyline, and also by systemic corticosteroids and by topiramate. Nystagmus, diplopia and extraocular muscle palsies can occur with antiepileptic drugs, particularly phenytoin and carbamazepine. Ocular neuromyotonia can follow parasellar radiation. Congenital ocular malformations can result from in utero exposure to maternally prescribed sodium valproate, phenytoin and carbamazepine. Neurologists must be aware of potential ocular toxicity of these drugs, and appropriately monitor for potential adverse events.
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PMID:Ocular complications of neurological therapy. 1595 88

Microemulsion systems composed of Span20/80+Tween20/80+n-butanol+H2O+isopropyl palmitate (IPP)/isopropyl myristate (IPM) were investigated as model systems of drug carriers for eye drops. Effects of chloramphenicol, normal saline, sodium hyaluronate and various oils on the phase behavior were studied. The phase transition was investigated by the electrical conductivity measurements. The electrical conductivity of the microemulsion was affected by the encapsulation of the drug into the system, and the addition of normal saline and sodium hyaluronate. The chloramphenicol is used to treat the diseases such as trachoma and keratitis. However, this drug in the common eye drops hydrolyzes easily. The main product of the hydrolysis is glycols. Here, the chloramphenicol was trapped into the oil-in-water (o/w) microemulsions and its stability was investigated by the high performance liquid chromatography (HPLC) assays in the accelerated experiments of 3 months. Its location in the microemulsion formulations was determined by means of 1H NMR spectroscopy. The results of HPLC revealed that the contents of the glycols in the microemulsion formulations were much lower than that in the commercial eye drops at the end of the accelerated experiments. It implied that the stability of the chloramphenicol in the microemulsion formulations was increased remarkably. The NMR experiments confirmed that the chloramphenicol molecules should be trapped into the hydrophilic shells of the microemulsion drops, which was composed of many oxyethylene groups. The nitro-groups of the chloramphenicol molecules were near the alpha2-CH2 of the surfactant molecules and the benzene rings of the chloramphenicol molecules were near the oxyethylene groups of the surfactant molecules. It was this reason that enabled the chloramphenicol molecules in the microemulsions to be screened from the bulk water and its stability to be increased remarkably.
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PMID:Phase behavior of the microemulsions and the stability of the chloramphenicol in the microemulsion-based ocular drug delivery system. 1603 10

The experiment has provided evidence for the safe use of 0.1% aqueous sodium hypochlorite for ocular tissues and for its therapeutic efficacy in purulent keratitis. The therapeutic effect is achieved by accelerating the lysis of neurotic tissues, by suppressing the pathogenic microflora, by alleviating an inflammatory reaction, by stimulating epithelization and reparative regeneration, by activating the phagocytic properties of neutrophilic leukocytes by 1.8-times, by increasing their functional reserves by 1.3 times as compared to the similar parameters observed in the use of conventional treatments.
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PMID:[Experimental study of the efficiency of use of sodium hypochlorite in the complex treatment of purulent keratitis]. 1640 66


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