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[Mechanism of keratinocyte growth factor-2 accelerating corneal epithelial wound healing on rabbit alkali burned cornea].

OBJECTIVE: To evaluate the curative effect of KGF-2 on the alkali-injured rabbit eye and to investigate the mechanism of KGF-2 accelerating corneal epithelial wound healing. METHODS: Alkali burn was produced in 24 corneas from 24 New Zealand rabbits. Four groups were randomly divided. Three groups (A, B, and C groups) were treated with KGF-2 solution (1, 50, 100 microg/ml, respectively), and one group (D group) was treated with phosphate-buffered saline (PBS) solution. The injured eyes were photographed after the fluorescence staining with a slit lamp and the pictures were analyzed with computer-aided picture analysis system to calculate the rate of corneal epithelial healing. Morphologic and immunohistological examinations (using P63, AE5 and EGFR antibodies) of the cornea were performed. RESULTS: KGF-2 at dosages ranging from 1 microg/ml to 100 microg/ml could enhance the cornea wound healing process. After 24 hours, epithelial healing rate of the 100 microg/ml KGF-2 group and the PBS treated group was 74% and 40%, respectively (P < 0.05). The corneal epithelial healing rate of each group was variable after four days and achieved complete healing after ten days. The P63 positive cells in KGF-2 groups appeared not only in the limbal area but also in the central area. For example, on the seventh day, in the limbal area, the P63 positive cells in the 100 microg/ml KGF-2 group, the PBS treated group and the normal group were 53.8 +/- 2.6, 29.5 +/- 2.2 and 17.0 +/- 2.1, respectively (P = 0.000). At the same time, the P63 positive cells in the non-limbal area in the 100 microg/ml KGF-2 group, the PBS treated group and the normal group were 69.5 +/- 2.8, 19.5 +/- 2.8 and 0, respectively (P = 0.000). CONCLUSIONS: These results suggested KGF-2 can stimulate the limbal epithelial stem cells to migrate to the central cornea. KGF-2 can accelerate the healing of alkali burned cornea.

Alkalies↗

[Studies on ocular alkali burn estimated by the component change of tear fluid and aqueous humor].

In this report, we aimed at examining biochemically the ocular surface damage caused by alkali burn. We used a low concentration of NaOH (less than 0.1 N) and examined the relationship between the ocular surface damage and the concentration of NaOH by examining the changes in components that have been released from corneoconjunctival tissues to the tear fluids by alkali burns, and we also examined the effects of eye rinsing and using topical ophthalmic agents. As a result, NaOH of more than 0.03 N was proven to cause the ocular surface damage. The changes of glutathione in tear fluids showed two peaks during the repair process and that coincided with the morphological changes. By measuring the released quantities of three components (glutathione, ascorbic acid and protein) with the use of three methods of alkali burns (corneoconjunctival pooling method, corneal cylinder method and conjunctival pooling method), we could estimate the slight corneoconjunctival damage using one sample biochemically. Moreover, the importance of eye rinsing was quantitatively demonstrated.

Alkalies↗

[Reactions of fluoride with hydroxyapatite powders--especially on the formation of alkali-soluble and -insoluble fluorides].

Synthetic hydroxyapatite (HA) powders were treated for varying time (1-60 min.) with neutral sodium fluoride solution of varying concentrations (10(0)-10(4) ppm). The alkali-soluble and -insoluble fluorides formation were studied independently of each other following their separation in molar potassium hydroxide. The total fluoride uptake by HA and its alkali-soluble and/or -insoluble fluoride contents were both found to be linearly related to the logarithm of the ionic fluoride level in the treatment solution, except for the outstandingly high figures in 10(4) ppm F solution. Further, the alkali-soluble/-insoluble fluoride rates were found in the same manner above. From the present results, it was suggested that the less treatment period (e.g. 1 min.) could sufficiently be effective in the fluoride painting. Further, the usefulness of frequent application with lower fluoride concentration was also suggested.

Alkalies↗

Decreased synthesis of alkali-soluble glucan in a cell-wall mutant of Saccharomyces cerevisiae.

In vivo studies and quantitative measurements of glucans provide evidence for a decreased rate of synthesis and a lower amount of alkali-soluble glucan in cells of the osmotically fragile VY1160 mutant of the yeast Saccharomyces cerevisiae. Combined genetic and biochemical analysis shows that the srb1 mutation is responsible for the reduction of alkali-soluble glucan. Data on beta(1----3) glucan synthase activity did not indicate the participation of the enzyme in the in vivo synthesis of alkali-soluble glucan and suggest the existence of other glucan synthases in Saccharomyces cerevisiae.

Alkalies↗

Standard models of corneal injury using alkali-immersed filter discs.

Central corneal alkali burn injuries were induced in rabbits by applying five NaOH concentrations on uniformly soaked 7 mm filter paper discs. Clinical parameters were evaluated daily by microscopic examination and photography, and corneal myeloperoxidase levels were measured periodically. Satisfactory alkali burn models of corneal inflammation, vascularization and ulceration were developed by manipulating the alkali concentration.

Alkalies↗

The efficacy of topical citrate after alkali injury is dependent on the period of time it is administered.

The neutrophilic response in the alkali-injured rabbit cornea can be separated into two peaks: the first from 12-24 hr and the second at 21 days. In the experiments detailed here, alkali-injured rabbit eyes were treated for 0-7 days (early peak), 6-35 days (late peak), or 0-35 days (both peaks) with 6.5% or 10% topical citrate. Clinical evaluation of these eyes showed that treatment with 10% citrate (0-35 days) significantly reduced the incidence and severity of corneal ulceration from the control level. When 10% citrate was administered to block the early neutrophilic peak, the incidence of corneal ulceration was also significantly reduced (33.3% from 72.2%). The average ulcer depth increased gradually, reaching an intermediate level well below the control group by day 35. In contrast, 10% citrate treatment of the late peak had no significant effect on the incidence of ulceration; however, these ulcers were less severe than those in the control. When 6.5% topical citrate (0-35 days) was used, there was a significant reduction in the severity but not the incidence of ulceration. In addition, the beneficial effects obtained from separate treatment of the early and late PMN peaks were mostly lost. These experiments suggest that both the early and late peak of the PMN response after alkali injury are important to the development of corneal ulcers. We hypothesize that the early use of 10% citrate diminishes the initial peak of PMNs, interfering with the release of self-perpetuating inflammatory mediators, thereby decreasing the later accumulation of PMNs that cause ulceration.

Administration, Topical↗

Dynamics of corneal epithelial healing after an alkali burn. A statistical analysis.

A precise definition of epithelial healing kinetics following chemical injury is necessary to aid the investigation of control mechanisms, potential therapeutic intervention and ophthalmic drug toxicity. Wound healing was studied photographically at frequent intervals in rabbits following 1N or 4N alkali burns. Planar wound areas were determined by computerized planimetry and transformed mathematically to curved surface data. The decrease in equivalent wound radius with time was computer-modelled using two linear and three nonlinear regressions. A periodic function was also investigated. Serial photographs showed that intermittent attrition of small areas of the migrating wound edge was a common confounding variable. Although excellent coefficients of determination were found for all models, the addition of nonlinear factors gave a small advantage. A mean lag phase of 3.96 and 6.52 hr occurred after 1N and 4N alkali burns, respectively; wound edge attrition was notably prevalent in early healing. Epithelial healing in the rabbit had a fundamental linear component, with mean epithelial migration rates of 76 and 80 microns/hr after 1N and 4N alkali burns, respectively, and which continued to closure. A quadratic nonlinear component was also suggested. No significant circadian component was detected.

Alkalies↗

Effects of dimethyl sulfoxide on a model of corneal alkali injury.

The potential role of dimethyl sulfoxide in minimizing early structural damage to the eye following corneal alkali injury was examined. Corneal alkali injury was induced in rabbits and treated with topical applications of 20% dimethyl sulfoxide. At day 3 the rates of corneal opacification (p less than 0.01) and corneal ulceration (p less than 0.05) were significantly lower in the treatment group than in the control group, but this effect was not sustained during the rest of the study period. Further work is required to determine the therapeutic value of topical dimethyl sulfoxide in combination with other agents, such as cycloplegics, corticosteroids, ascorbic acid and citric acid, in corneal alkali injury.

Alkalies↗

Studies on acid protease fractions and gastric mucosal atrophy. 2. Relationship of acid proteases in gastric juice separately determined by alkali treatment and gastric mucosal atrophy.

The relationships of two acid protease groups, alkali labile pepsin (ALP) and alkali stable pepsin (ASP), and gastric mucosal atrophy, were studied. ALP and ASP were determined separately by alkali treatment. The extent of fundic gland atrophy was detected by endoscopic congo red test. The subjects of the study were 10 normal subjects and 64 patients with gastroduodenal disease. In all subjects, both ALP and ASP outputs were increased by tetragastrin administration while ASP:ALP ratio was decreased by the provocation. ALP output was reduced in parallel with the extent of fundic gland atrophy whereas ASP output was kept until the atrophy became severe.

Adult↗

Ascorbic acid prevents corneal ulceration and perforation following experimental alkali burns.

Depressed aqueous humor glucose and ascorbic acid levels returned to control values within 14 days following a 20 sec, 6 mm. diameter, 1N sodium hydroxide burn of the rabbit cornea. These corneas did not ulcerate or perforate. After a 20 sec., 12 mm. diameter, 1N sodium hydroxide burn, aqueous humor glucose levels returned to normal values, but ascorbic acid levels remained significantly depressed for up to 30 days. These corneas became markedly ulcerated in about 60 per cent of animals and frequently perforated. Following 12 mm. alkali burns, rabbits treated daily with 1.5 Gm. of subcutaneous ascorbic acid rarely developed corneal ulcerations and the corneas did not perforate. It is suggested that exogenous maintenance of adequate aqueous humor levels of ascorbic acid overcomes the relatively scorbutic state of the anterior segment induced by a 12 mm. alkali burn, thereby impairing the development of corneal ulceration and perforation. Elevated aqueous humor levels of ascorbic acid had no influence on corneal epithelial cell migration patterns following alkali burns.

Alkalies↗

Immunosuppression and selective inflammatory cell depletion. Studies on a guinea pig model of corneal ulceration after ocular alkali burning.

Total ocular-surface alkali burning was performed on guinea pigs to study the effects of generalized immunosuppression and selective inflammatory cell line modifications on corneal ulceration. Central stromal corneal ulceration developed in 86% (18/21) of control eyes three to seven days after alkali burning, whereas ulcers developed in only 16% (3/19) of the eyes of guinea pigs immunosuppressed with cyclophosphamide. Neutrophils, the preponderant inflammatory cells in ulcerating corneas, were conspicuously absent from the nonulcerating corneas. Selective neutrophil suppression by intravenous administration of a highly specific anti-guinea pig neutrophil serum also suppressed the development of corneal ulcerations in this model; in only 25% of the eyes so treated did ulcers develop after alkali burning. T lymphocyte or monocyte modifications with similar monospecific antisera had no effects on the rate of corneal ulceration. Neutrophil depletion after the onset of ulceration halted progression of the corneal ulcer.

Animals↗

Collagen shields exacerbate ulceration of alkali-burned rabbit corneas.

OBJECTIVE: To determine the impact of collagen shields on ulceration of rabbit corneas after alkali burn. METHODS: After a 60-second 2N sodium hydroxide burn to rabbit corneas, 24-hour collagen shields were placed on the corneas daily for 21 days; control corneas did not receive collagen shields. The extent of corneal ulceration was documented daily for 21 days by slit-lamp examination of treated and control eyes. Three separate studies were performed using collagen shields from two commercial sources. RESULTS: In the three studies, corneas in the collagen shield-treated eyes began to ulcerate sooner than those in the control group; the corneas in collagen shield-treated eyes also began to perforate sooner. At 21 days after alkali injury, the mean (+/- SE) corneal ulceration score in the collagen shield-treated rabbits was 4.1 +/- 0.17 (descemetocele formation) compared with 2.7 +/- 0.28 (midstromal ulceration) in controls. This difference was significant at P < .005. CONCLUSION: Collagen shield treatment results in marked acceleration of corneal ulceration and perforation after alkali injury.

Animals↗

Alkali- and heat-treated porous titanium for orthopedic implants.

This study was carried out to investigate the effects of the alkali and heat treatments on the bone-bonding behavior of porous titanium implants. Porous titanium implants had a 4.6 mm solid core and a 0.7 mm thick porous outer layer using pure titanium plasma-spray technique. Three types of porous implants were prepared from these pieces: 1.control implant (CL implant) as manufactured 2.AW-glass ceramic bottom-coated implant (AW implant) in which AW-glass ceramic was coated on only the bottom of the pore of the implant 3.alkali- and heat-treated implant (AH implant), where implants were immersed in 5 mol/L NaOH solution at 60 degrees C for 24 h and subsequently heated at 600 degrees C for 1 h. The implants were inserted into bilateral femora of six dogs hemi-transcortically in a randomized manner. At 4 weeks, push-out tests revealed that the mean shear strengths of the CL, AW, and AH implants were about 10.8, 12.7, and 15.0 MPa, respectively. At 12 weeks there was no significant difference between the bonding strengths of the three types of the porous implants (16.0-16.7 MPa). Histologically and histomorphologically, direct bone contact with the implant surface was significantly higher in the AH implants than the CL and AW implants both at 4 and 12 weeks. Thus, the higher bonding strength between bone and alkali- and heat-treated titanium implants was attributed to the direct bonding between bone and titanium surface. In conclusion, alkali and heat treatments can provide porous titanium implants with earlier stable fixation.

Animals↗

Alkali-metal ion/molecule association reactions and their applications to mass spectrometry

This review will be concerned primarily with thermal alkali-metal ion association reactions of the general type: A+ + M + N reversible (A + M)+ + N. Where A denotes a positively charged alkali metal ion, M is neutral species and N works as a third body. As indicated, most association reactions are reversible, and the A-M bond derives primarily from electrostatic forces whose energy (affinity) is typically 50 kcal/mol or less, often much less. The review includes reaction mechanism, instrumentation, and application to mass spectrometry, together with reaction rates and alkali ion affinities of the classified compounds.

Journal Article↗

Ligand design for alkali-metal-templated self-assembly of unique high-nuclearity CuII aggregates with diverse coordination cage units: crystal structures and properties.

The construction of two unique, high-nuclearity Cu(II) supramolecular aggregates with tetrahedral or octahedral cage units, [(mu(3)-Cl)[Li subset Cu(4)(mu-L(1))(3)](3)](ClO(4))(8)(H(2)O)(4.5) (1) and [[Na(2) subset Cu(12)(mu-L(2))(8)(mu-Cl)(4)](ClO(4))(8)(H(2)O)(10)(H(3)O(+))(2)](infinity) (2) by alkali-metal-templated (Li(+) or Na(+)) self-assembly, was achieved by the use of two newly designed carboxylic-functionalized diazamesocyclic ligands, N,N'-bis(3-propionyloxy)-1,4-diazacycloheptane (H(2)L(1)) or 1,5-diazacyclooctane-N,N'-diacetate acid (H(2)L(2)). Complex 1 crystallizes in the trigonal R3c space group (a = b = 20.866(3), c = 126.26(4) A and Z = 12), and 2 in the triclinic P1 space group (a = 13.632(4), b = 14.754(4), c = 19.517(6) A, alpha = 99.836(6), beta = 95.793(5), gamma = 116.124(5) degrees and Z = 1). By subtle variation of the ligand structures and the alkali-metal templates, different polymeric motifs were obtained: a dodecanuclear architecture 1 consisting of three Cu(4) tetrahedral cage units with a Li(+) template, and a supramolecular chain 2 consisting of two crystallographically nonequivalent octahedral Cu(6) polyhedra with a Na(+) template. The effects of ligand functionality and alkali metal template ions on the self-assembly processes of both coordination supramolecular aggregates, and their magnetic behaviors are discussed in detail.

Journal Article↗

Elevated-temperature metathesis syntheses of structurally novel alkali-metal tetrakis(3,5-di-tert-butylpyrazolato)lanthanoidate(III) complexes: toluene-coordinated discrete bimetallic complexes and supramolecular chains.

Sodium and potassium tetrakis(3,5-di-tert-butylpyrazolato)lanthanoidate(III) complexes [M[Ln(tBu(2)pz)(4)]] have been prepared by reaction of anhydrous lanthanoid trihalides with alkali metal 3,5-di-tert-butylpyrazolates at 200-300 degrees C, and a 1,2,4,5-tetramethylbenzene flux for M=K. On extraction with toluene (or occasionally directly from the reaction tube) the following complexes were isolated: [Na(PhMe)[Ln(tBu(2)pz)(4)]] (1 Ln; 1 Ln=1 Tb, 1 Ho, 1 Er, 1 Yb), [K(PhMe)[Ln(tBu(2)pz)(4)]].2 PhMe (2 Ln; 2 Ln=2 La, 2 Sm, 2 Tb, 2 Ho, 2 Yb, 2 Lu), [Na[Ln(tBu(2)pz)(4)]](n) (3 Ln; 3 Ln=3 La, 3 Tb, 3 Ho, 3 Er, 3 Yb), [K[Ln(tBu(2)pz)(4)]](n) (4 Ln; 4 Ln=4 La, 4 Nd, 4 Sm, 4 Tb, 4 Ho, 4 Er, 4 Yb, 4 Lu), with the last two classes generally being obtained by loss of toluene from 1 Ln or 2 Ln, and [Na(tBu(2)pzH)[Ln(tBu(2)pz)(4)]].PhMe (5 Ln; 5 Ln=5 Nd, 5 Er, 5 Yb). Extraction with 1,2-dimethoxyethane (DME) after isolation of 2 Ho yielded [K(dme)[Ho(tBu(2)pz)(4)]] (6 Ho). X-ray crystal structures of 1 Ln (=1 Tb, 1 Ho; P2(1)/c), 2 Ln (=2 La, 2 Sm, 2 Tb, 2 Yb, 2 Lu; Pnma), 3,4 Ln (=3 La, 3 Er, 4 Sm; P2(1)/m), and 5 Ln (=5 Nd, 5 Er, and 5 Yb; P1) show each group to be isomorphous regardless of the size of the Ln(3+) ion. All complexes contain eight-coordinate [Ln(eta(2)-tBu(2)pz)(4)] units. These are further linked to the alkali metal by bridging through two (1,2,5 Ln) or three (3,4 Ln) tBu(2)pz groups which show striking coordination versatility. Sodium is coordinated by an eta(4)-PhMe, a micro-eta(2):eta(2)-tBu(2)pz, and a micro-eta(4)(Na):eta(2)(Ln)-tBu(2)pz ligand in 1 Ln, and by one eta(1)-tBu(2)pzH and two micro-eta(3)(Na):eta(2)(Ln) ligands in 5 Ln. By contrast, potassium has one eta(6)-PhMe and two micro-eta(5)(K):eta(2)(Ln) ligands in 2 Ln. Classes 3,4 Ln form polymeric chains with the alkali metal bonded by two micro-eta(3)(NNC-M):eta(2)(Ln)-tBu(2)pz ligands within [MLn(tBu(2)pz)(4)] units which are joined together by eta(1)(C)-tBu(2)pz-Na, K linkages.

Journal Article↗

Molecular switch triggered by solvent polarity: synthesis, Acid-base behavior, alkali metal ion complexation, and crystal structure.

The synthesis and characterization of the new tetraazamacrocycle L, bearing two 1,1'-bis(2-phenol) groups as side-arms, is reported. The basicity behavior and the binding properties of L toward alkali metal ions were determined by means of potentiometric measurements in ethanol/water 50:50 (v/v) solution (298.1+/-0.1 K, I=0.15 mol dm(-3)). The anionic H(-1)L(-) species can be obtained in strong alkaline solution, indicating that not all of the acidic protons of L can be removed under the experimental conditions used. This species behaves as a tetraprotic base (log K(1)=11.22, log K(2)=9.45, log K(3)=7.07, log K(4)=5.08), and binds alkali metal ions to form neutral [MH(-1)L] complexes with the following stability constants: log K(Li)=3.92, log K(Na)=3.54, log K(K)=3.29, log K(Cs)=3.53. The arrangement of the acidic protons in the H(-1)L(-) species depends on the polarity of the solvents used, and at least one proton switches from the amine moiety to the aromatic part upon decreasing the polarity of the solvent. In this way two different binding areas, modulated by the polarity of solvents, are possible in L. One area is preferred by alkali metal ions in polar solvents, the second one is preferred in solvents with low polarity. Thus, the metal ion can switch from one location to the other in the ligand, modulated by the polarity of the environment. A strong hydrogen-bonding network should preorganize the ligand for coordination, as confirmed by MD simulations. The crystal structure of the [Na(H(-1)L)].CH(3)CN complex (space group P2(1)/c, a=12.805(1), b=20.205(3), c=14.170(2) A, beta=100.77(1) degrees, V=3601.6(8) A(3), Z=4, R=0.0430, wR2=0.1181), obtained using CH(2)Cl(2)/CH(3)CN as mixed solvent, supports this last aspect and shows one of the proposed binding areas.

Journal Article↗

An alkali digestion method to expose connective tissue fibers: a scanning electron microscopy study of rat lung.

Alkali digestion has been used to remove cellular elements of tissues thus exposing the underlying connective tissue framework. We studied the action of this severe alkali treatment on the delicate tissues of rat lung. The lungs of male Sprague-Dawley rats were perfused with saline to remove blood and then inflated by fixation through the airways at 20 cm pressure. Sections of lung 2 x 5 x 5 mm were immersed in 2.5 M NaOH at 25 degrees C for 6 h, 16 h, 24 h, 48 h, and 72 h. The alkali was changed daily. Tissues were washed to neutral with water (24 h), treated with tannic acid (1%, 3h), post-fixed with osmic acid (1%, 3 h) and processed for SEM. At 6 h, epithelial cells started to peel off the alveolar surface. At 16 h the digestion process was well advanced. At 48 h the cells were completely removed revealing the lattice network of connective tissue fibers within the alveolar surface. The method allows the complete removal of cellular elements of the lung while retaining the very fine 3D structure of the connective tissue matrix.

Animals↗