[The influence of VEGF inhibitors on corneal endothelium after injection into the anterior chamber in a porcine eye model]. / Einfluss von VEGF-Inhibitoren auf das Hornhautendothel bei Injektion in die Vorderkammer am Modell des Schweineauges.

BACKGROUND: The injection of antiangiogenic agents, such as ranibizumab (Lucentis®) and bevacizumab (Avastin®) into the anterior chamber of the eye represents a suitable alternative for treating neovascular glaucoma by reducing intraocular pressure. OBJECTIVES: As the antiangiogenic substances are in direct contact with the sensitive corneal endothelium, the aim of this study was to show the effects of intracameral injection of ranibizumab and bevacizumab on this cell layer. METHODS: Each injection consisted of 50 µl containing either ranibizumab (0.5 mg/0.05 ml), bevacizumab (1.25 mg/0.05 ml) or triamcinolone containing benzyl alcohol (2 mg/0.05 ml) which was used as the control group. These compounds were injected into the anterior chamber of pig eyes. Afterwards the corneas were dissected, fixed, examined by a scanning electron microscopy and evaluated according to a specified score. Assessment of the endothelium was carried out by evaluating the condition of microvilli, cell borders, cell surface and cell pattern. The findings were compared to untreated corneas and those injected with 50 µl of balanced salt solution (BSS). RESULTS: The corneal endothelium exposed to the antiangiogenic substances showed only minor changes in comparison to the controls treated only with BSS. Also seen during this research was the irreversible cell damage in the control group using triamcinolone. CONCLUSION: Ranibizumab and bevacizumab have no damaging effects on the corneal endothelium when used in the anterior chamber. They can be administered as an intracameral injection for the treatment of rubeotic secondary glaucoma. Triamcinolon containing benzyl alcohol causes severe damage to the endothelial cells of the cornea by direct contact.

[The relationship between the temperature increase caused by phacoemulsification and the damage to the corneal endothelium]. / Zusammenhang zwischen der Temperatursteigerung bei der Phakoemulsifikation und den auftretenden Zellschäden am Hornhautendothel.

PURPOSE: Endothelial cell damage can be found after a phacoemulsification. The reason for this cell damage is not yet known. The temperature rise inside the anterior chamber during the emulsification of the lens is considered as a potential damage mechanism. The aim of this study was to investigate the relationship between the temperature increase and the cell damage. MATERIALS AND METHODS: This study was performed with 86 enucleated porcine eyes, which were divided into six groups A-F. Group A served as control group. Phacoemulsification was simulated in the groups B-E with different surgically relevant system settings. The temperature change was measured simultaneously with temperature sensors inside the anterior chamber. Inside the eyes of group F, the instruments were positioned and irrigation and aspiration were activated, but no ultrasound was applied. For all 86 corneas, the endothelial cell damage was quantified with a standardised evaluation protocol using scanning electron microscopy (SEM). A potential correlation was checked between the observed cell damage and the measured temperature rise. RESULTS: The highest temperature increase in group E with an obstructed aspiration line and an output power setting of 50 % was 17.77 °C. The temperature increase in group D with an output power setting of 100 % and unblocked fluid flow was significantly lower (p = 0.006). The highest temperature increase in group D was 8.89 °C. In contrast, the cells in group D were rated with a significantly lower score value than the cells in group E (p < 0.001). No significant correlation between the temperature rise and the cell damage could be obtained in due consideration of all measured data. However, an increase of the output power setting was connected with a non-linear increase of the cell loss. CONCLUSION: The temperature rise was not the main reason for the endothelial cell damage in the performed experiments. Therefore, there seems to be no causal relationship between the temperature increase inside the anterior chamber during a common phacoemulsification and the endothelial cell damage. Due to the strong dependence between the output power setting and the cell damage, the lowest output power setting should be used during surgery which ensures the emulsification of the nucleus.

[Handicapped patients and leisure sports--a chance for social integration]. / Behinderte Menschen im Urlaubssport--Eine Chance der sozialen Integration.

Organizing leisure time in an active way with lots of experiences is getting more and more important in western society. Accordingly, sports activities and travelling as well as their combination, holiday sports activities, are in great demand. A general idea of the literature in that field with regard to the possibilities and difficulties of handicapped persons is that holiday sports activities are considered apt to offer outstanding prerequisites for handicapped and nonhandicapped people getting closer to each other. Starting out on this basis, this survey is mainly dedicated to the following questions: What is the situation for handicapped persons in holiday sports activities? Is holiday sporting in a position to meet the expectations of social integration, and to what extent? A questionnaire about these items was answered by wheelchair users, making it clear, on the one hand, that there are hardly any offers for disabled people to take part in holiday sporting activities. On the other hand, the survey confirms that holiday sports activities are well suited to answer major demands of the integration issue, i.e., communication and interaction as well as other factors conducive to social integration. Subsequently, the author formulates the request that access to and participation in holiday sporting activities be made easier for disabled people so that greater use can be made of these special opportunities for social integration.

Visualization of gap junction mobility in living cells.

In order to study the dynamics of gap junctions in living cells, a cDNA was expressed in hepatocellular carcinoma-derived PLC cells coding for chimerical polypeptide Cx.EGFP-1, which consists of rat connexin32 and enhanced green fluorescent protein (EGFP). Cx.EGFP-1 was integrated into gap junctions, and the emitted epifluorescence reliably reported the distribution of the chimera. Therefore, stably transfected PLC clone PCx-9 was used to examine the dynamic behavior of gap junctions by time-lapse fluorescence microscopy. The pleomorphic fluorescent junctional plaques were highly motile within the plasma membrane. They often fused with each other or segregated into smaller patches, and fluctuation of fluorescence was detected within individual gap junctions. Furthermore, the uptake of junctional fragments into the cytoplasm of live cells was documented as originating from dynamic invaginations that form long tubulovesicular structures that pinch off. Endocytosis and subsequent lysosomal degradation, however, appeared to contribute only a little to the rapid gap junction turnover (determined half-life of 3.3 h for Cx.EGFP-1), since most cytoplasmic Cx.EGFP-1 fluorescence did not colocalize with the endocytosed fluid phase marker horseradish peroxidase or the receptor-specific endocytotic ligand transferrin and since it was distinct from lysosomes. Disassembly of gap junctions was monitored in the presence of the translation-inhibitor cycloheximide and showed increased endocytosis and continuous reduction of junctional plaques. Highly motile cytoplasmic microvesicles, which were detectable as multiple, weakly fluorescent puncta in all movies, are proposed to contribute significantly to gap junction morphogenesis by the transport of small subunits between biosynthetic, degradative, and recycling compartments.

Multiphoton ionization of molecules: A comparison between femtosecond and nanosecond laser pulse ionization efficiency.

Multiphoton ionization mass spectra of nonvolatile molecules laser desorbed into a supersonic beam are recorded. It is shown by indirect measurements that the laser desorption of neutrals is not mass limited, but lead to the formation of neutrals with intesities large enough for intense signals. To investigate the efficiency of the multiphoton ionization process with varying laser pulse durations, simultaneous laser pulses of 500 fs and 5 ns or 100 fs and 5 ns have been applied to the neutral beam. The energies of both femtosecond and nanosecond laser pulses are held in a comparable magnitude, and thus produce, in the resulting ion intensity, very large differences up to 4 orders of magnitude. For larger evaporated molecules (> 500 u) the ionization efficiency from nanosecond laser pulses drops significantly in comparison to femtosecond laser pulse excitation. A variety of possible reasons for the different ionization and dissociation behavior in femtosecond and nanosecond laser pulse excitations are discussed in this paper. It is rationalized that even with very short laser pulses and large molecules the "ladder switching model" for ionization and fragmentation is valid.

Oral immunization of foxes against rabies: practical experiences of a field trial in the Federal Republic of Germany.

The development of and the logistics used in campaigns for the oral immunization of foxes against rabies in the Federal Republic of Germany are described. The "Bavarian Model", which is outlined in detail, shows how local hunters were recruited for bait distribution and control measures at practically no cost. Over 10 million baits have been distributed in this way by hundreds of thousands of hunters in the Federal Republic of Germany as well as in the other European countries that participated in this large-scale field trial. As a result of the trial, rabies has been reduced or even eradicated in large parts of the Federal Republic of Germany.

Oral immunization of foxes against rabies: Practical experiences of a field trial in the Federal Republic of Germany

The development of and the logistics used in campaigns for the oral immunization of foxes against rabies in the Federal Republic of Germany are described. The "Bavarian Model", which is outlined in detail, shows how local hunters were recruited for bait distribution and control measures at practically no cost. Over 10 million baits have been distributed in this way by hundreds of thousands of hunters in the Federal Republic of Germany as well as in the other European countries that participated in this large-scale field trial

As a result of the trial, rabies has been reduced or even eradicated in large parts of the Federal Republic of Germany(AU)

Health problems after travel to developing countries.

Travelers to developing countries participated in a follow-up study of the health risks associated with short (less than three months) visits to these nations. Travelers to the Greek or Canary Islands served as a control cohort. Participants completed a questionnaire to elicit information regarding pretravel vaccinations, malaria prophylaxis, and health problems during and after their journey. Relevant infections were confirmed by the respondent's personal physician. The questionnaire was completed by 10,524 travelers; the answer rate was 73.8%. After a visit to developing countries, 15% of the travelers reported health problems, 8% consulted a doctor, and 3% were unable to work for an average of 15 days. The incidence of infection per month abroad was as follows: giardiasis, 7/1,000; amebiasis, 4/1,000; hepatitis, 4/1,000; gonorrhea, 3/1,000; and malaria, helminthiases, or syphilis, less than 1/1,000. There were no cases of typhoid fever or cholera.

[Viral hepatitis and AIDS-associated HTLV III/LAV virus infections in drug addicts]. / Virale Hepatitis und AIDS-assoziierte HTLV III/LAV-Virusinfektionen bei Drogenabhängigen.

In 1984 intravenous drug users accounted for 25% of all cases of acute hepatitis B and for 32% of all cases of non-A/non-B hepatitis recorded in the Canton of Zürich. Drug addicts also represented an important risk group for hepatitis A, which occurred in small epidemics. Among 141 "healthy" drug users, 10 (7%) individuals showed signs of ongoing hepatitis B virus (HBV-) infection, 26 (19%) individuals had the finding "anti-HBc-alone" (unresolved HBV-infection) and another 69 (49%) individuals were HBV-immune. 30%, 23% and 16% of the three above groups of individuals with HBV-markers were also anti-delta virus positive. Of the 141 "healthy" drug users 23 (16%) showed signs of an ongoing hepatitis A virus (HAV-) infection and 63 (45%) individuals were HAV-immune. Anti-HTLV III/LAV was detected in 69 (49%) of the i.v. drug users, with a higher prevalence (60%) in females than in males and with a higher prevalence in individuals with HBV-markers (50-62%) than in those without such markers (19%). Thus the i.v. drug users are at high risk for infections with hepatitis viruses A, B, D and those responsible for non-A/non-B hepatitis, as well as with the AIDS-associated virus HTLV III/LAV. Preventive measures should include a reduction of needle sharing and of promiscuity, which is abundantly practised by i.v. drug users.

Lactose carrier protein of Escherichia coli. Structure and expression of plasmids carrying the Y gene of the lac operon.

The previously described hybrid plasmid pC7 which carries lacI+O+delta(Z)Y+A+ on a 12.3 X 10(6)-Mr DNA fragment [Teather et al. (1978) Mol. Gen. Genet. 159, 239-248] was partially digested with the restriction endonuclease EcoRI under conditions reducing the recognition sequence to d(A-A-T-T) and ligated to the vector pB322. lac Y-carrying inserts of various sized (Mr 1.5-4.7 X 10(6)) were obtained. Hybrid plasmid pTE18 (2300-base-pair insert) carries part of the I (repressor) gene, the promotor-operator region, part of the Z (beta-galactosidase) gene, the Y (lactose carrier) gene and part of the A (transacetylase) gene. Upon induction of pTE18-harbouring strains the Y-gene product is expressed at a nearly constant rate for several generations and accumulates to a level of 12-16% of the total cytoplasmic membrane protein. Integration into the membrane leads to active carrier as judged by binding and transport measurements.

Lactose carrier protein of Escherichia coli. Transport and binding of 2'-(N-dansyl)aminoethyl beta-D-thiogalactopyranoside and p-nitrophenyl alpha-d-galactopyranoside.

The elevated level of lactose carrier protein present in cytoplasmic membranes derived from Escherichia coli strain T31RT, which carries the Y gene of the lac operon on a plasmid vector (Teather, R. M., et al. (1978) Mol. Gen. Genet. 159, 239--248), has allowed the detection of a complex between the carrier and the fluorescent substrate 2'-(N-dansyl)-aminoethyl beta-D-thiogalactopyranoside (Dns2-S-Gal). Binding is accompanied by a 50-nm blue shift in the emission maximum of the dansyl residue. The complex (dissociation constant, KD = 30 micron) rapidly dissociates upon addition of competing substrates such as beta-D-galactopyranosyl 1-thio-beta-D-galactopyranoside or upon reaction with the thiol reagent p-chloromercuribenzenesulfonate. Binding of both Dns2-S-Gal and p-nitrophenyl alpha-D-galactopyranoside (alpha-NPG) occurs spontaneously in the absence of an electrochemical potential gradient across the membrane. Comparison of equilibrium binding experiments using Dns2-S-Gal or alpha-NPG and differential labeling of the carrier with radioactive amino acids shows that the carrier binds 1 mol of substrate per mol of polypeptide (molecular weight 30 000). In addition to specific binding to the lactose carrier, Dns2-S-gal binds unspecifically to lipid vesicles or membranes, as described by a partition coefficient, K = 60, resulting in a 25-nm blue shift in the emission maximum of the dansyl group. Both Dns2-S-Gal and alpha-NPG are not only bound by the lactose carrier but also transported across the membrane by this transport protein in cells and membrane vesicles. The fluorescence changes observed with dansylated galactosides in membrane vesicles in the presence of an electrochemical gradient (Schuldiner et al. (1975) J. Biol. Chem. 250, 1361--1370)) are interpreted as an increase in unspecific binding after translocation.