Biomedical subjects

O Hockwin

Publications and source records attributed to O Hockwin.

At least 55 records · Page 3Linked to original sources

PubMed1990

Reproducibility studies with the Zeiss SLC system and animal cataract models.

Scheimpflug photography has become the basic method for documentation of lens transparency changes in clinical and experimental ophthalmology, due to its high reproducibility. In animal cataract studies, the reproducibility is strongly influenced by the handling characteristics of the camera used, due to limited cooperation of the animal. The reproducibility of the Zeiss SLC system, which offers a direct quality control of the image on the video screen, was tested with 2 animal cataract models, the ultraviolet B (UVB)-induced cataract and the true diabetic cataract in the Brown-Norway rat. 10 rats each of the 2 cataract models and of an untreated control group were photographed in a random order on 3 occasions on the same day by the same photographer. Quality control and densitometry were performed by the same system operator, the measurement window was positioned standardly, coincident with the optical axis of the eye. Statistical comparison was carried out in the capsular layer, that is the area of initial cataract development in both models, and in the cortical layer, into which the diabetic cataract progresses during its later stages of development. The nuclear layer was also evaluated, but has no direct relation to one of the models employed. The results clearly indicate that the reproducibility is predominantly influenced by the homogeneity or inhomogeneity of the cataract model employed. The system operator and the photographer provided that they are well trained, have minor influence on the reproducibility of the Zeiss SLC system.

Animals↗

PubMed1990

Imaging characteristics of three cameras using the Scheimpflug principle.

We studied the handling and the potentials of three different cameras operating according to the Scheimpflug principle and which currently are commercially available. The examinations were performed with the cameras Topcon SL-45, Topcon SL-6E with cataract attachment and Zeiss SLC system. Pigmented Brown-Norway rats with ultraviolet-B-induced cataract were used as the examination model. The image characteristics of the three cameras can be summarized as follows: The Topcon SL-45 camera produces very sharp images with small distortion; the Tocpon SL-6E camera with cataract attachment has the advantage to record simultaneously a slit image and a retroillumination image on the same film frame, but the slit image is quite distorted at the vertical axis; as regards the Zeiss SLC system, the quality of the video image is not as good as a film negative; however, this camera offers a superimposed image to the observer for easy orientation, as for example with small animal eyes. In addition, the direct quality control of the image on the screen increases the reproducibility significantly. However, the slit image is quite distorted at the horizontal axis.

Animals↗

PubMed1990

Ultraviolet filter photography to demonstrate the fluorescence of animal lenses with different cataract models.

Ultraviolet (UV) filter photography with the Topcon SL-45 Scheimpflug camera has provided valuable informations about age-related and cataract-type-dependent changes in the spectral properties of the human lens. The present study deals with the same phenomenon in normal lenses of the Brown-Norway rat and in those with true diabetic and naphthalene cataracts. The lenses of all animals of the 3 groups were photographed at the middle and final examination of a 6-week experiment on Kodak Tri-X-pan ASA 400 black-and-white film, using visible light (xenon flash) and UV-filtered light (320-390 nm transmission) from the same light source for recording. The results clearly demonstrate that both cataract models exhibit characteristic fluorescence properties, different from each other and from normal rat lenses. The naphthalene cataract shows the most drastic increase in fluorescence in the cortex, compared to the increase in scattering with visible light. The versatility of the method in preclinical research and the versatility of the cataract models open new aspects of drug-related research in drug toxicity studies.

Animals↗

PubMed1990

Water-insoluble high-molecular-weight and alpha-crystallins as the source of the Scheimpflug light scattering pattern in the rat lens.

Lenses of 14-week-old rats were separated into 10 layers or fractions by a frozen-sectioning technique. The biochemical characteristics of these layers were assigned to corresponding parts of the densitometric reading obtained from the Scheimpflug negative, which enables a correlation of light scattering values recorded in vivo to protein patterns in the same area. Calculated as percentage of lens dry weight, all water-soluble crystallins show minima and the water-insoluble crystallins show maxima in the lens nucleus. This demonstrates that the nucleus contains the bulk of the water-insoluble high-molecular-weight and alpha-crystallins, being the source for the Scheimpflug light scattering pattern.

Animals↗

PubMed1990

Lens safety study with Picumast dihydrochloride--a double masked study using the Scheimpflug method.

A double-masked study was performed to investigate a possible side effect of the antiallergic substance Picumast dihydrochloride on lens transparency. 372 patients with Picumast dihydrochloride- or Ketotifen-treatment regularly underwent ophthalmologic examinations and Scheimpflug photography of the anterior eye segment. Results of slitlamp examinations as well as microdensitometric analyzes of the film negatives after one year treatment did not reveal any evidence that Picumast dihydrochloride compromised lens transparency in humans.

Asthma↗

PubMed1990

[The worth of anti-cataract drugs].

Lens opacities in the elderly occur as different types of cataracts in various regions of the lens. This variation is the manifestation of different pathomechanisms. None of the "anti-cataract" preparations on the market at present state the particular pathomechanism or type of cataract for which its application is recommended. Investigations to elucidate the mode of action by preclinical studies or adequate experimental cataract models have only been carried out in a few cases. For most of the preparations, the determination of the efficacy of the "component substances" or of "the substances supposed to be effective" at the target site of the lens is not even available. For about 10 years now, procedures have been at hand for performing objective tests on the efficacy of anticataract preparations. These qualifications have so far been met by only four of the licensed anticataract preparations. In these cases, it was shown that the progress of disturbances or opacities localized in certain defined layers of the lens could be delayed. However, there is still no preparation available that might be considered as generally effective in cases of "senile cataract". Also, experimental research and the development of novel substances have been only successful in certain cataract models with defined types of opacities. It is therefore questionable whether ophthalmologists should further prescribe preparations with the diffuse indication "senile cataract", especially as verification of their efficacy and preclinical data are often missing.

Aged↗

PubMed1990

Comparison of Scheimpflug-photography, specular microscopy and scanning electron microscopy to detect corneal changes in toxicity studies in rats.

With an increasing number of in-vivo methods to examine the eyes of laboratory animals, the rat has become an important animal model in experimental eye research. Specular microscopy is a clinical tool to examine the corneal endothelium in-vivo. To evaluate the versatility of this method for small animal eyes, we studied both corneal endothelial cell-count and corneal thickness in normal rats as well as those with diabetic, naphthalene and UV-B cataract. As a reference scanning electron microscopy (SEM) of the corneal endothelium was performed. For cell-counts the correlation coefficient between both methods was found to be sufficient. The comparison of corneal thickness measurement (SEM-values) with specular microscopy and with Scheimpflugbiometry failed to show a satisfactory correlation. The study proves that specular microscopy is a useful tool to document changes also in the endothelium of the rat-cornea.

Animals↗

PubMed1990

Crystallin profiles of calf and bovine lens microsections, stained for free sulfhydryl groups and proteins.

Calf and bovine lenses of 0.98 and 8.40 years old were separated mechanically into lens equator and inner cylinder. The inner cylinder was cut into 10 to 11 sections by a microsectioning device. These sections were investigated on the protein profiles of water-soluble crystallins, stained for proteins by Coomassie Blue (CB). These crystallins were also specifically stained purple for free sulfhydryl groups (SH). It appeared that all crystallins that were stained blue for proteins were also stained purple for sulfhydryl groups. This means that all crystallins contain free sulfhydryl groups. Going from anterior and posterior cortex to the nucleus of the lens, there was an appreciable increase of the percent of gamma-crystallins, whereas especially in the older lenses a decrease of gamma-crystallins could be observed in the lens equator and the anterior and posterior cortices. A stainability factor F = %SH/%CB was calculated for all crystallins. HM-, alpha- and beta s-crystallins exhibit high values of factor F. For the bovine lens, factor F of HM-crystallin displayed a maximum in the nucleus, whereas this factor decreased for gamma-crystallins towards the nucleus. This microsectioning technique allows for determining age-related differences between the sections obtained. This may lead to a comprehensive understanding of age-related changes within one lens, including cataractous changes.

Aging↗

PubMed1990

Lipid analysis in bovine lens parts after in vitro incubation in the presence of an HMG-CoA-reductase inhibitor.

Normal bovine lenses and bovine lenses after incubation in TC 199 in the presence of a lipid lowering drug were divided into four parts: the equatorial ring, the nucleus, the anterior cortex and posterior cortex. The lipids were extracted according to Egge et al. (1). Total lipids were determined gravimetrically, the lipid fractions phospholipids (PL), cardiolipin (CL), free fatty acids (FFA) and cholesterol (CH) were separated by thin layer chromatography and determined quantitative by densitometry after charring with 10% sulfuric acid. There are differences in lipid distribution between the four lens compartments, but there are no differences between normal and drug treated lenses in total lipids and lipid fractions. This result could be explained in different ways: either during this incubation time of 24 hours at 37 degrees C there will be no effect on the lens epithelial cells or there is no de-novo synthesis of lipids, especially of cholesterol in the bovine lens epithelium which could be influenced by lipid lowering drugs like HMG-CoA reductase inhibitors.

Animals↗

PubMed1990

Investigations on the presence of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA-reductase, E.C.1.1.1.34) in lenses of various animal species.

The cholesterol requirements of the lens for the formation of plasma membranes are met by self-synthesis immediately after birth, this capacity, however, decreases considerably with increasing age, so that the deficit can only be met by exogenous supply. These findings are of great importance with respect to the qualitative assessment of extra-hepatical side effects of the substance class of HMG-CoA-reductase inhibitors on possible disturbances of lens transparency. In contrast to investigations of Mosley et al. (23) with rat and rabbit lenses, we did not find any activity of the HMG-CoA-reductase in our experiments with the lens cortex of calf, bovine, Beagle dog. The disturbances in lens transparency observed in chronical toxicity tests with high doses of HMG-CoA- reductase inhibitors might rather be due to the impairment of the exogenous cholesterol supply by a considerable decrease of the normal cholesterol level in the blood. The therapeutical treatment of pathologically increased blood cholesterol levels of patients should therefore not affect the transparency of human lenses. Relevant drug-safety-clinical studies confirm this experimentally substantiated supposition.

Animals↗

PubMed1990

No lens changes caused by simvastatin results from a prospective drug safety study.

45 patients suffering from a primary hypercholesterolemia were treated with Simvastatin. Additionally to internal visits regular ophthalmologic examinations were performed. The main interest concerning the ophthalmologic examination was directed toward the documentation and measurement of lens opacities by means of Scheimpflug photography. Moreover, every 6 months a complete regular ophthalmologic examination was carried out. We present the results after a time period of 2 years. Relevant changes in clinical findings could not be found. In some patients the Scheimpflug measurement revealed an increase in light scattering. These findings, however, were within the limit of normal age related changes.

Adult↗

PubMed1990

Ocular drug-safety study with the HMG-CoA reductase inhibitor pravastatin.

35 pravastatin-treated patients with familial hypercholesterolemia were included in an ocular drug-safety study. Besides general examinations performed by the department of internal medicine a complete ophthalmological examination with special respect to lens opacities was carried out at the beginning, followed by control visits every six months. Scheimpflug photography of the eyes and densitometric image analysis provided objective data on lens transparency. After 18 months of treatment there is no evidence for any pathological lens changes induced by the drug applied. A decrease in visual acuity of 0.2 or more as seen in two eyes was not accompagnied by a corresponding increase in lens opacities. These observations correspond with the results of other HMG-CoA reductase inhibitors tested so far.

Anterior Eye Segment↗

PubMed1990

Evaluation of a possible cocataractogenic potential of Ofloxacin.

Ofloxacin, a new antibiotic of the group of quinolones, was tested for its possible cocataractogenic potential. Two cataract models of the rat, the naphthalene cataract and the true diabetic cataract were used, cataract development in-vivo was monitored with the slit lamp microscope and documented with the Scheimpflug camera Topcon SL-45. After a six weeks observation and treatment period, where Ofloxacin was dosed with 20 mg/kg body weight daily with a stomach tube, the animals were sacrificed and their lenses used for biochemical analyses. Although the results of Scheimpflug photography showed that the combination of the 2 cataract models together with the Ofloxacin treatment lead to higher densities in the cortical layer, a marked cocataractogenic potential could not be demonstrated. Also the biochemical data made it evident, that Ofloxacin has no obvious cocataractogenic potential, neither single nor in combination with 1 or 2 cataract models.

Animals↗

PubMed1990

Post-mortem biochemistry of beagle dog lenses after treatment with Fluvastatin (Sandoz) for 2 years at different dose levels.

Post-mortem biochemical analyses of dog lenses and of aqueous humour of a 2 year oral toxicity study in the dog with Fluvastatin (control, 1, 8 and 16 mg/kg/day) did not show any relationship to the observed lens opacities (3 animals out of 8 at 16 mg/kg/day). With respect to lens transparency, a daily dosage of 8 mg/kg/day Fluvastatin to dogs over a period of 2 years is non-cataractogenic. Mean data on lenticular enzyme activities (GPX, G6PH, GAPDH, ALD, AR, LDH, PFK and SDH) as well as measurements of GSH/GSSG, ATP, ADP, AMP, Gluc, Fruc, Sorb, G6P and F6P do not indicate changes which may directly lead to lens opacifications. Conformational changes of lens proteins (heat lability of PFK-activity), a shift in the albumin/IgG ratio of aqueous humour and equatorial lens protein composition changes (after isoelectrofocusing) were observed. The biological significance of these changes is unknown as the non-cataractogenic dose for lens opacities in beagle dogs is 8 mg/kg/day.

Animals↗

PubMed1989

Testing a possible cocataractogenic potential of befunolol (Glauconex) with animal cataract models.

Befunolol was tested in an animal experiment with 2 cataract models of the Sprague-Dawley-rat. The treatment scheme was designed with 8 different treatment groups, such that befunolol could be tested single and in combination with one or two cataract models. Over the 6 weeks experimental period, slit lamp microscopy and Scheimpflug photography were employed as observation and documentation methods, extensive post-mortem biochemistry was carried out after sacrifice of the animals. Neither the in-vivo observation and documentation nor the biochemistry showed pronounced effects pointing to a cocataractogenic potential of the drug. Slit density enhancing effects were found in combining UV-B irradiation and befunolol treatment. This effect has also been found in other experiments with timolol.

Animals↗

PubMed1989

Bendazac lysine in selected types of human senile cataract. A long-term double-masked placebo-controlled clinical trial with multilinear densitometric image analysis of Scheimpflug photographs.

A double-masked placebo-controlled clinical trial with hard data evaluation by image analysis of Scheimpflug photographs taken at baseline and 6, 12 and 18 months after starting treatment was performed to assess the efficacy of bendazac lysine in four different types of senile cataract. The study had a classical split-plot design. For statistical evaluation, the analysis of variance and covariance for repeated measures were used for three different lens sections: anterior capsule and superficial layer, anterior cortex and nucleus. In the entire group of 53 evaluable patients (without separation into cataract-type subgroups), there was a significantly less increase over time in light scattering (i.e. film blackening) of the anterior cortex and nucleus with bendazac lysine than with placebo. There was also a strong trend in favour of the active drug at the anterior capsular level. Patients with water clefts and spokes showed a significantly less light scattering of the anterior capsule and cortex when treated with bendazac lysine. Those with nuclear changes also showed significantly less light scattering of the anterior cortex and nuclear region with the active drug than with placebo. The number of patients with subcapsular and wedge-shaped (cuneiform) cataracts was too small to be adequately assessed by statistical procedures. Nevertheless, there were indications of a beneficial effect of bendazac lysine on all the lens sections in patients with subcapsular cataracts and on the anterior cortical region in those with wedge-shaped cataracts. In conclusion, this study showed that the increase in light scattering over time, i.e. the progression of cataract, is less in bendazac lysine-treated patients than in those treated with placebo.

Adult↗

PubMed1989

Improved biometry of the anterior eye segment.

In this paper, a method is presented to evaluate the true values of several optical parameters of the anterior eye segment. These are: the thicknesses of the cornea and lens, the depth of the anterior chamber and the anterior and posterior curvatures of the cornea and lens. First, a photo is taken of each patient's eye with a Topcon SL-45 Scheimpflug camera. There are two effects distorting the photo. As the film plane and the object plane are perpendicular to each other, the imaging scale is not constant over the photo, a phenomenon which is called the camera distortion. As the light passes through different refractive media on its way from the inner structures of the eye to the camera, the rays of light are refracted, which is called the refractive distortion of the eye. Following these distortions, the proportions on the photo do not correspond to those in the human eye. The intention of this paper is to calculate the true optical parameters of the anterior eye segment. The seeming optical parameters are taken from the photo and the path of light from a point in the film plane through the camera and the refracting surfaces into the eye is constructed by ray tracing. A set of representative points calculated according to ray tracing provides a basis to evaluate the true optical parameters. This work is done using a Basic program, that accepts the seeming parameters from the photo as input values and provides the true values as output. The adjectives seeming and true added to the optical parameters indicate a value correlating with a distorted photo and a value that was corrected by the theory. The two terms were chosen by mnemonic reasons, although another pair of adjectives such as distorted and corrected might have been of higher precision. For an average adult human eye the optical parameters from the photo were compared with the calculated ones. A phantom eye with well-known optical parameters was constructed and photos were taken from this eye to verify the calculations.

Anterior Eye Segment↗

PubMed1989

Determination of AL01576 concentration in rat lenses and plasma by bioassay for aldose reductase activity measurements.

Investigations on the disposition of the highly effective aldose reductase inhibitor AL01576 were carried out in pigmented rats after oral dosing and topical administration of a 0.1% ophthalmic suspension by means of an assay modified from a previously described method measuring aldose reductase activity. The crude enzyme extract of pig lenses was used as a test system. From the activity remaining after addition of the plasma or lens extracts, the concentration could be determined since the inhibition constant (IC50) of AL01576 is known. With this procedure, the concentration of AL01576 in plasma and lenses of Brown-Norway rats given different doses of the drug for 42 consecutive days were determined and compared with a gas chromatographic assay technique. These data indicate that AL01576 is absorbed into the lens with a substantial portion redistributing into the lens following systemic delivery. Drug concentrations were correlated with efficacy measurements, though they were lower in an animal group treated with naphthalene to provoke cataract formation. In a second animal series with Brown-Norway rats over 5 days, AL01576 was administered three times per day to the right eye only. During the washout period, AL01576 had a long persistence in plasma and lenses following this short-term topical ocular administration.

Aldehyde Reductase↗