Influence of latanoprost on retinal microcirculation in glaucoma.

PURPOSE: To test whether latanoprost has an influence on ocular haemodynamics, considering the general reputation of prostaglandins which is frequently associated with vasoconstriction. The effect of latanoprost on the retinal blood supply of treatment-naïve glaucoma patients was tested. MATERIALS AND METHODOLOGY: 13 patients (7 male, 6 female) who had just recently been diagnosed with primary open-angle glaucoma (POAG) were treated with latanoprost (0.005%). The average age of our study group was 63.8 years (+/- 2.9 years). The drug's effect on retinal autoregulation was assessed by flicker test using the Dynamic Vessel Analyzer (DVA). Examinations took place before initializing treatment, after 4 weeks and once again after 4 to 6 months. RESULTS: In our group of POAG patients, the IOP under treatment was significantly reduced about 25%. No intraindividual differences in systemic blood pressure and heart rate were observed. In DVA measurements of glaucoma patients, the maximum flicker dilation of the arteries was significantly lower than reported for healthy volunteers. Beyond that, POAG patients did not show significant differences in vessel diameters, peak amplitudes as well as maximum dilations of retinal arteries and veins before and under treatment with latanoprost (0.005%). CONCLUSION: Latanoprost markedly lowered the IOP but it did not exert a significant effect on retinal haemodynamics. There was neither a tendency towards vasoconstriction nor towards vasodilation. Sustaining reperfusion damage after topical latanoprost therapy thus seems to be highly unlikely. Further studies must show if sole IOP lowering or a dual positive effect - IOP lowering and improvement of retinal vessel autoregulation - have a more positive impact on the long term follow-up of glaucoma patients.

[Malignant epibulbar tumours: new strategies in diagnostics and therapy]. / Maligne epibulbäre Tumoren: Neue Strategien in Diagnostik und Therapie.

In this article we discuss the complex diagnostic approaches and therapeutic options for the most important conjunctival malignancies. Conjunctival melanoma can be a diagnostic challenge as it can be difficult to distinguish from benign melanocytic conjunctival tumours. Complete surgical excision accompanied by a coherent adjuvant concept is the key for a curative therapy. Moderate and severe conjunctival intraepithelial neoplasias (CIN) are precancerous lesions and can progress to invasive squamous cell carcinoma. The involvement of large parts of the ocular surface can prevent an R 0-resection. Adjuvant therapeutic concepts are therefore especially important to gain tumour control and preserve the function of the affected eye. Lymphomas are the most common malignant primary tumours of the orbit and ocular adnexa. They can present as primary or secondary tumours of the conjunctiva, the lacrimal gland, the orbital fat, the eye lid or the lacrimal sac. The most common manifestation site of ocular MALT lymphoma is the conjunctiva with 20 - 33 % of all epibulbar lymphomas. More than 75 % of ocular lymphoma patients develop only one lymphomatous lesion. Immunophenotyping allows the exact differentiation between the lymphoma entities. Infectious agents (e.g., Chlamydia psittaci) seem to play a role in the pathogenesis. An overview over radiotherapeutic approaches that are conclusively applicable at the conjunctiva completes the article.

[Topical Mitomycin C as a therapy of conjunctival tumours]. / Topisches Mitomycin C als Therapie konjunktivaler Tumore.

Surgical excision with tumour free margins is the gold standard for squamous cell and melanocytic tumours of the conjunctiva. In cases of diffuse and extensive tumours a complete surgical excision is sometimes not possible. Therefore, alternative or adjuvant therapies are required. Topical chemotherapy with mitomycin C (MMC) is increasingly finding use in clinical practice. MMC has several advantages such as good tolerability and mild side effects. Present studies have shown that mitomycin C is a good option in squamous cell neoplasia of the conjunctiva. However, further multi-centre studies and long-term follow-up are needed.The results in treating melanocytic tumours of the conjunctiva with MMC are less convincing. MMC seems to be an option for the treatment of primary acquired melanosis (PAM); but, if the tumour is suspicious for melanoma primary chemotherapy with MMC is obsolete. In these cases MMC can only be used as an adjuvant therapy, otherwise tumour control is not assured. However, prospective randomized controlled trials are necessary for a final evaluation of MMC therapy in melanocytic tumours of the conjunctiva.

Survival of Campylobacter jejuni in water: effect of grazing by the freshwater crustacean Daphnia carinata (Cladocera).

Environmental studies of the human-pathogenic bacterium Campylobacter jejuni have focused on linking distributions with potential sources. However, in aquatic ecosystems, the abundance of C. jejuni may also be regulated by predation. We examine the potential for grazing by the freshwater planktonic crustacean Daphnia carinata to reduce the survival of C. jejuni. We use a system for measuring grazing and clearance rates of D. carinata on bacteria and demonstrate that D. carinata can graze C. jejuni cells at a rate of 7% individual(-1) h(-1) under simulated natural conditions in the presence of an algal food source. We show that passage of C. jejuni through the Daphnia gut and incorporation into fecal material effectively reduces survival of C. jejuni. This is the first evidence to suggest that grazing by planktonic organisms can reduce the abundance of C. jejuni in natural waters. Biomanipulation of planktonic food webs to enhance Daphnia densities offers potential for reducing microbial pathogen densities in drinking water reservoirs and recreational water bodies, thereby reducing the risk of contracting water-borne disease.

Down-regulation of intrinsic P-glycoprotein expression in multicellular prostate tumor spheroids by reactive oxygen species.

Intrinsic expression of the multidrug resistance (MDR) transporter P-glycoprotein (Pgp) may be regulated by reactive oxygen species (ROS). A transient expression of Pgp was observed during the growth of multicellular tumor spheroids. Maximum Pgp expression occurred in tumor spheroids with a high percentage of quiescent, Ki-67-negative cells, elevated glutathione levels, increased expression of the cyclin-dependent kinase inhibitors p27Kip1 and p21WAF-1 as well as reduced ROS levels and minor activity of the mitogen-activated kinase (MAPK) members c-Jun amino-terminal kinase (JNK), extracellular signal-regulated kinase ERK1,2, and p38 MAPK. Raising intracellular ROS by depletion of glutathione with buthionine sulfoximine (BSO) or glutamine starvation resulted in down-regulation of Pgp and p27Kip1, whereas ERK1,2 and JNK were activated. Down-regulation of Pgp was furthermore observed with low concentrations of hydrogen peroxide and epidermal growth factor, indicating that ROS may regulate Pgp expression. The down-regulation of Pgp following BSO treatment was abolished by agents interfering with receptor tyrosine kinase signaling pathways, i.e. the protein kinase C inhibitors bisindolylmaleimide I (BIM-1) and Ro-31-8220, the p21ras farnesyl protein transferase inhibitor III, the c-Raf inhibitor ZM 336372 and PD98059, which inhibits ERK1,2 activation. ROS involved as second messengers in receptor tyrosine kinase signaling pathways may act as negative regulators of Pgp expression.

Pelagic Bacteria-Particle Interactions and Community-Specific Growth Rates in Four Lakes along a Trophic Gradient.

Abstract The relationships between bacterial concentration, bacterial production, and cell-specific activity of both free and attached bacteria and environmental factors such as suspended solids, nutrients, and temperature were examined in four lakes, two in New Zealand and two in Switzerland. Estimates of cell-specific production were obtained by microautoradiographic counts of [3H]thymidine-labeled cells. Bacteria attached to particles accounted for only 1.3 to 11.6% of the total bacterial abundance, but showed overall 20-fold higher specific growth rates and were relatively more active than their free counterparts. On average, 80 to 100% of epibacteria were attached to organic particles. The abundance and production of free and attached bacteria were positively correlated; however, relationships between these fractions and some environmental variables differed. Cell-specific activities of active bacteria were not equivalent to mean cellular activities of the entire bacterial community and differed in their relationship to trophic state. [3H]Thymidine-positive bacteria were more tightly linked to chlorophyll a than were total bacteria. Our findings indicate that production by attached bacteria, fueled by phytoplankton carbon, supplies "new" free bacteria to the bacterial community. Our results support the idea that particulate organic matter acts as a source of dissolved nutrients to free bacteria. Bottom-up control of bacterial biomass, as shown by regressions of biomass vs production, appeared to be stronger in two ultraoligotrophic lakes than in two more eutrophic ones.

The spatial structure of the physical environment.

There is substantial environmental variance at small spatial scales (1 m or less) in both natural and disturbed environments. We have investigated the spatial structure of physical variables at larger scales (up to 106 m). We analysed surveys of edaphic properties of Wisconsin forest soils, of the water chemistry of lakes in Ontario and Labrador, and of temperature and precipitation in northeastern North America. We found no clear indication that the variance among sites approaches some maximal value as the distance between them increases. We suggest instead that the variance of the physical environment tends to increase continually with distance. The slope of the log-log regression of variance on distance provides a means of comparing the heterogeneity of different environments with respect to a given factor, or of comparing different factors within a given environment. This slope provides a useful measure of environmental structure that can be related to the biodiversity or plasticity of native organisms.

Solutions to problems in enumerating sediment bacteria by direct counts.

We examined the effect of different sediment types on the staining effectiveness of the fluorochrome DAPI (4'-6-diamidino-2-phenylindole dihydrochloride) over a wide range of concentrations and on the masking effect of sediment particles on DAPI-stained bacteria. Sediment type greatly affects the staining efficiency of DAPI, and most published studies seem to have underestimated bacterial abundances by using suboptimal concentrations of the fluorochrome. A DAPI concentration of 5 mug ml is required to effectively stain the bacteria in most sediments that can be sampled with a gravity corer. When the sediments are diluted 687 times (a dilution factor similar to those most often used in the literature), sediment particle masking of stained bacteria is highly variable for different sediment types. By using a measure of turbidity (A(750)) to indicate masking and the quartz-corrected water content as a measure of the initial (in situ) dilution of each sediment type, it becomes possible to show a linear relationship between masking and the integrated (initial x experimental) dilution of various sediments. This relationship allows the development of a correction procedure for masking which makes accurate and unbiased counts possible. Data so obtained show a strong relationship between bacteria (cells per milliliter of fresh sediment) and sediment organic matter (grams [dry weight] per milliliter of fresh sediment), one that is not discernable without the correction. The proposed method of staining and correction for sediment masking provides the basis for a standardized interpretation of sediment bacterial counts.