Calprotectin as Diagnostic Marker for Hepatic Encephalopathy and Spontaneous Bacterial Peritonitis in Cirrhosis.

BACKGROUND: Calprotectin is a well-established marker for intestinal inflammation, mainly in inflammatory bowel disease, and represents one of the most studied biomarkers in stool samples. METHODS: Apart from its important diagnostic role in inflammatory bowel disease, there are few studies showing that calprotectin can also be used as a diagnostic tool in patients suffering from hepatic encephalopathy (HE) and spontaneous bacterial peritonitis (SBP) in cirrhosis. RESULTS: Since calprotectin concentration in the human stool or in ascites is elevated at an early stage of inflammation, it might serve as an early screening tool for patients suffering from cirrhosis who are at risk to develop these conditions. As detection and monitoring of HE and SBP may be unclear and resource-intensive, identification of valid new markers of disease activity is necessary. In this review, we summarize the current knowledge of calprotectin as a diagnostic biomarker in cirrhosis, indicating that it is a highly promising diagnostic surrogate marker to screen for the presence of HE and SBP. CONCLUSIONS: To screen cirrhotic patients for SBP, calprotectin should be assessed in ascitic fluid while it should be measured in feces when screening for HE. However, the value of calprotectin in managing individual patients must be considered in the specific clinical context.

Colectomy with ileostomy for severe ulcerative colitis-postoperative complications and risk factors.

PURPOSE: In the era of biological therapy of ulcerative colitis (UC), surgical treatment frequently consists of colectomy, end ileostomy, and rectal stump closure before patients go on towards restorative proctocolectomy. We aimed to evaluate possible risk factors for the occurrence of postoperative complications and investigate those after initial colectomy in these patients. METHODS: Retrospective analysis of 180 patients (76 female, 104 male) undergoing colectomy for UC with formation of a rectal stump and terminal ileostomy between March 2008 and March 2018 at Charité University Hospital Berlin, Campus Benjamin Franklin. A panel of possible postoperative complications was established, patient history was screened, and postoperative complications were analyzed using the Clavien Dindo Classification. RESULTS: Postoperative complication rate was 27.7%. Mortality was 0.5%. Postoperative ileus occurred in 15.3% and rectal stump leakage in 14.8%. Complications were categorized as Clavien Dindo 3 in 80%. Risk factors for surgical complications after multivariate analysis were ASA classification (p = 0.004), preoperative anemia (Hemoglobin < 8 mg/dl) (p = 0.025), use of immunosuppressants (p = 0.003), more than two cardiovascular diseases (p = 0.016), and peritonitis (p = 0.000). Reoperation rate of patients with surgical complications was 27.7%. CONCLUSION: Colectomy in high-risk UC patients is associated with significant morbidity. However, most of the surgical complications can be treated conservatively. Overall mortality is low. Patient-related risk factors are associated with postoperative complications. Optimizing these risk factors or earlier indication for surgery in the course of UC may help to reduce morbidity of this procedure.

Exploiting Oligo(amido amine) Backbones for the Multivalent Presentation of Coiled-Coil Peptides.

The investigation of coiled coil formation for one mono- and two divalent peptide-polymer conjugates is presented. Through the assembly of the full conjugates on solid support, monodisperse sequence-defined conjugates are obtained with defined positions and distances between the peptide side chains along the polymeric backbone. A heteromeric peptide design was chosen, where peptide K is attached to the polymer backbone, and coiled-coil formation is only expected through complexation with the complementary peptide E. Indeed, the monovalent peptide K-polymer conjugate displays rapid coiled-coil formation when mixed with the complementary peptide E sequence. The divalent systems show intramolecular homomeric coiled-coil formation on the polymer backbone despite the peptide design. Interestingly, this intramolecular assembly undergoes a conformational rearrangement by the addition of the complementary peptide E leading to the formation of heteromeric coiled coil-polymer aggregates. The polymer backbone acts as a template bringing the covalently bound peptide strands in close proximity to each other, increasing the local concentration and inducing the otherwise nonfavorable formation of intramolecular helical assemblies.

A phase I pharmacokinetic and safety analysis of epothilone folate (BMS-753493), a folate receptor targeted chemotherapeutic agent in humans with advanced solid tumors.

Background The folate receptor alpha is selectively over-expressed in a number of human cancers. BMS-753493 is a folate conjugate of the epothilone analog BMS-748285 that was designed to selectively target folate receptor expressing cancer cells. Methods BMS-753493 was investigated in two parallel multi-institutional first-in-human phase I/IIa studies in patients with advanced solid tumors. In Study 1, patients were treated on a schedule of once daily dosing of BMS-753493 administered on Days 1, 4, 8 and 11 every 21 days with a starting dose of 5 mg daily and in Study 2, patients were treated once daily on Days 1-4 every 21 days, with a starting dose of 2.5 mg daily. Results A total of 65 patients were treated across the two studies. The maximum tolerated dose (MTD) was 26 mg in Study 1 and 15 mg in Study 2. Fatigue, transaminitis, gastrointestinal toxicity, and mucositis were dose-limiting toxicities. One patient in Study 2 developed Stevens-Johnson syndrome attributed to BMS-753493. Plasma exposures of both the conjugated and free epothilone increased in a dose related fashion in both studies and the half-life of the conjugated epothilone was 0.2-0.6 h across dose levels. No objective tumor responses were seen in either study. Conclusions BMS-753493 was generally tolerable and toxicities known to be associated with epothilone class of anticancer agents were common, although peripheral neuropathy and neutropenia appear to have been less frequent and less severe as compared to epothilones. Antitumor activity was not demonstrated and further development of BMS-753493 has been discontinued.

Assessment of the biological effects of welding fumes emitted from metal inert gas welding processes of aluminium and zinc-plated materials in humans.

The aim of this study was to investigate biological effects and potential health risks due to two different metal-inert-gas (MIG) welding fumes (MIG welding of aluminium and MIG soldering of zinc coated steel) in healthy humans. In a threefold cross-over design study 12 male subjects were exposed to three different exposure scenarios. Exposures were performed under controlled conditions in the Aachener Workplace Simulation Laboratory (AWSL). On three different days the subjects were either exposed to filtered ambient air, to welding fumes from MIG welding of aluminium, or to fumes from MIG soldering of zinc coated materials. Exposure was performed for 6 h and the average fume concentration was 2.5 mg m(-3). Before, directly after, 1 day after, and 7 days after exposure spirometric and impulse oscillometric measurements were performed, exhaled breath condensate (EBC) was collected and blood samples were taken and analyzed for inflammatory markers. During MIG welding of aluminium high ozone concentrations (up to 250 µg m(-3)) were observed, whereas ozone was negligible for MIG soldering. For MIG soldering, concentrations of high-sensitivity CRP (hsCRP) and factor VIII were significantly increased but remained mostly within the normal range. The concentration of neutrophils increased in tendency. For MIG welding of aluminium, the lung function showed significant decreases in Peak Expiratory Flow (PEF) and Mean Expiratory Flow at 75% vital capacity (MEF 75) 7 days after exposure. The concentration of ristocetin cofactor was increased. The observed increase of hsCRP during MIG-soldering can be understood as an indicator for asymptomatic systemic inflammation probably due to zinc (zinc concentration 1.5 mg m(-3)). The change in lung function observed after MIG welding of aluminium may be attributed to ozone inhalation, although the late response (7 days after exposure) is surprising.

Quantitative mapping of glycoprotein micro-heterogeneity and macro-heterogeneity: an evaluation of mass spectrometry signal strengths using synthetic peptides and glycopeptides.

Mass spectrometry has made possible the field of proteomics and become an invaluable tool for identifying and quantifying post-translational modifications of proteins from complex mixtures. Because PTMs are recognized as key factors of biological activity, reliable PTM characterization is essential to understanding the relationship between protein isoform and activity. Protein glycosylations, in particular, can be especially difficult to characterize due to the range of different oligosaccharide entities that may be attached at any particular site. In this month' Special Feature Dr Daniel Kolarich of the Dept. of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces and his collaborators point out that quantitative label-free glycoproteomics can yield information about glycoprotein microand macroheterogeniety if the tools are sufficiently accurate. To understand and characterize the performance capability of MS tools they synthesized a panel of peptides and their glycopeptide derivatives as references and used these to investigate the qualitative and quantitative results from various ionization techniques and mass analyzers.

Mapping the 3D distribution of CdSe nanocrystals in highly oriented and nanostructured hybrid P3HT-CdSe films grown by directional epitaxial crystallization.

Highly oriented and nanostructured hybrid thin films made of regioregular poly(3-hexylthiophene) and colloidal CdSe nanocrystals are prepared by a zone melting method using epitaxial growth on 1,3,5-trichlorobenzene oriented crystals. The structure of the films has been analyzed by X-ray diffraction using synchrotron radiation, electron diffraction and 3D electron tomography to afford a multi-scale structural and morphological description of the highly structured hybrid films. A quantitative analysis of the reconstructed volumes based on electron tomography is used to establish a 3D map of the distribution of the CdSe nanocrystals in the bulk of the films. In particular, the influence of the P3HT-CdSe ratio on the 3D structure of the hybrid layers has been analyzed. In all cases, a bi-layer structure was observed. It is made of a first layer of pure oriented semi-crystalline P3HT grown epitaxially on the TCB substrate and a second P3HT layer containing CdSe nanocrystals uniformly distributed in the amorphous interlamellar zones of the polymer. The thickness of the P3HT layer containing CdSe nanoparticles increases gradually with increasing content of NCs in the films. A growth model is proposed to explain this original transversal organization of CdSe NCs in the oriented matrix of P3HT.

The effect of dentin desensitizer on shear bond strength of conventional and self-adhesive resin luting cements after aging.

This study tested the impact of Gluma Desensitizer on the shear bond strength (SBS) of two conventional (RelyX ARC, Panavia 21) and two self-adhesive (RelyX Unicem, G-Cem) resin luting cements after water storage and thermocycling. Human third molars (N=880) were embedded in acrylic resin. The buccal dentin was exposed. Teeth were randomly divided into four main groups, and the following cements were adhered: 1) RelyX ARC, 2) Panavia 21, 3) RelyX Unicem, and 4) G-Cem. In half of the teeth in each group, dentin was treated with Gluma Desensitizer. In the conventional cement groups, the corresponding etchant and adhesive systems were applied. SBS of the cements was tested after 1 hour (initial); at 1, 4, 9, 16, and 25 days of water storage; and at 1, 4, 9, 16, and 25 days of thermocycling. SBS data were analyzed by one-way analysis of variance (ANOVA); this was followed by the post hoc Scheffé test and a t-test. Overall, the highest mean SBS (MPa) was obtained by RelyX ARC (ranging from 14.6 ± 3.9 to 17.6 ± 5.2) and the lowest by Panavia 21 in combination with Gluma Desensitizer (ranging from 0.0 to 2.9 ± 1.0). All tested groups with and without desensitizer showed no significant decrease after aging conditions compared with baseline values (p>0.05). Only the Panavia 21/Gluma Desensitizer combination showed a significant decrease after 4 days of thermocyling compared with initial values and 1 day thermocycling. Self-adhesive cements with Gluma Desensitizer showed increased SBS after aging conditions (ranging from 7.4 ± 1.4 to 15.2 ± 3) compared with groups without desensitizer (ranging from 2.6 ± 1.2 to 8.8 ± 2.9). No cohesive failures in dentin were observed in any of the test groups. Although self-adhesive cements with and without desensitizer presented mainly adhesive failures after water storage (95.8%) and thermocyling (100%), conventional cement (RelyX ARC) showed mainly mixed failures (90.8% and 89.2%, after water storage and thermocyling, respectively). Application of the Gluma Desensitizer to dentin before cementation had a positive effect on the SBS of self-adhesive cements.

Metformin attenuates ovarian cancer cell growth in an AMP-kinase dispensable manner.

Metformin, the most widely used drug for type 2 diabetes activates 59 adenosine monophosphate (AMP)-activated protein kinase (AMPK), which regulates cellular energy metabolism. Here, we report that ovarian cell lines VOSE, A2780, CP70, C200, OV202, OVCAR3, SKOV3ip, PE01 and PE04 predominantly express -α(1), -ß(1), -γ(1) and -γ(2) isoforms of AMPK subunits. Our studies show that metformin treatment (1) significantly inhibited proliferation of diverse chemo-responsive and -resistant ovarian cancer cell lines (A2780, CP70, C200, OV202, OVCAR3, SKVO3ip, PE01 and PE04), (2) caused cell cycle arrest accompanied by decreased cyclin D1 and increased p21 protein expression, (3) activated AMPK in various ovarian cancer cell lines as evident from increased phosphorylation of AMPKα and its downstream substrate; acetyl co-carboxylase (ACC) and enhanced ß-oxidation of fatty acid and (4) attenuated mTOR-S6RP phosphorylation, inhibited protein translational and lipid biosynthetic pathways, thus implicating metformin as a growth inhibitor of ovarian cancer cells. We also show that metformin-mediated effect on AMPK is dependent on liver kinase B1 (LKB1) as it failed to activate AMPK-ACC pathway and cell cycle arrest in LKB1 null mouse embryo fibroblasts (mefs). This observation was further supported by using siRNA approach to down-regulate LKB1 in ovarian cancer cells. In contrast, met formin inhibited cell proliferation in both wild-type and AMPKα(1/2) null mefs as well as in AMPK silenced ovarian cancer cells. Collectively, these results provide evidence on the role of metformin as an anti-proliferative therapeutic that can act through both AMPK-dependent as well as AMPK-independent pathways.

From randomized trial to practice: single institution experience using the GOG 172 i.p. chemotherapy regimen for ovarian cancer.

BACKGROUND: The objective of the study was to evaluate completion rates and toxic effects of an i.p. chemotherapy regimen in a cross-section of nonselected patients with ovarian cancer (OC). PATIENTS AND METHODS: All patients with stage IIIC OC consecutively operated at our institution from January 2006 to December 2007 were prospectively collected and analyzed. RESULTS: Eighty-nine patients with stage IIIC OC optimally debulked were evaluated for this study. An i.p. port was primarily placed in 53 of 89 (60%), and i.p. chemotherapy was recommended in 55 patients. Reasons for not recommending i.p. chemotherapy in patients optimally debulked included postoperative complications (n = 7: 8%), poor nutritional/functional status (n = 5: 6%), and extensive surgery including bowel resection (n = 9: 10%). Thirty-three patients (33/55: 60%) recommended to receive i.p. chemotherapy-initiated i.p. treatment. Fifty-two percent of those beginning i.p. therapy (17/33) received three or more cycles with 36% (12/33) successfully completing six cycles. Reasons for discontinuation included grade 3-4 nephrotoxicity in 3 of 21 (14%), febrile neutropenia/sepsis in 3 of 21 (14%), port infection or malfunction in 8 of 21 (38%). CONCLUSIONS: The i.p. chemotherapy regimen used in a consecutive cohort of patients carries could be completed in only a small percentage of patients. Less toxic regimens with higher acceptability should be considered.

Phase I trial of autologous hematopoietic SCT with escalating doses of topotecan combined with CY and carboplatin in patients with relapsed or persistent ovarian or primary peritoneal carcinoma.

We designed a phase I clinical trial of escalating doses of topotecan with CY and carboplatin in combination with autologous hematopoietic SCT (AHSCT) for the treatment of relapsed or persistent platinum sensitive ovarian or primary peritoneal carcinoma. After stem cell collection, 16 patients received topotecan at 1.5, 2.5, 3.5, 4.5 or 6.0 mg/m(2)/d combined with CY 1.5 g/m(2)/d and carboplatin 200 mg/m(2)/d, all by 4-day continuous infusion. Steady state pharmacokinetics of topotecan and carboplatin were examined. Pre-treatment biopsies were examined for the expression of topoisomerase (topo) I, Ki67 and Bcl-2 family members by immunohistochemistry. One of six patients at a topotecan dose of 4.5 mg/m(2)/d and two of three patients at 6.0 mg/m(2)/d had dose-limiting toxicity of grade 3 stomatitis lasting >2 weeks. There was no treatment-related mortality. As topotecan clearance was constant over the dose range examined, topotecan steady state plasma concentrations increased with dose. Median progression-free survival and overall survival were 6.5 months and 2.7 years, respectively. Shorter progression-free survival was observed in tumors with low topo expression (P=0.04). Topotecan can safely be dose escalated to 4.5 mg/m(2)/d in combination with CY, carboplatin and AHSCT. This trial is registered at ClinicalTrials.gov as NCT00652691.

Clinical and ultrasonographic correlation between scapular dyskinesia and subacromial space measurement among junior elite tennis players.

OBJECTIVES: In this study, the hypothesis that tennis players with scapular dyskinesia present a smaller subacromial space than non-athletes was investigated. Additionally, the correlation between the size of the subacromial space and abnormalities in scapular movement during arm abduction was studied. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 53 elite tennis players and 20 control participants were enrolled in the study. Participation was restricted to elite-level, junior tennis players who had no current shoulder pain or history of shoulder injuries. INTERVENTION: Each individual was examined for scapular dyskinesia by a single physician and by ultrasound, with the results analysed in a blind fashion by a single radiologist. RESULTS: 43.4% of the tennis players and 20% of control participants presented with scapular dyskinesia. Of the 106 shoulders evaluated, 39.6% of tennis players and 10% of control participants presented with scapular dyskinesia in the clinical examination (p = 0.005). Ultrasonographic measurements demonstrated that tennis players presented statistically smaller subacromial spaces compared with control participants (p<0.001). A decrease in the subacromial space was observed in tennis players when the shoulder was raised from 0 degrees to 60 degrees of abduction; however, dyskinesia-afflicted athletes demonstrated a significantly greater decrease following this movement (19.3 vs 13.8 mm, p = 0.002). CONCLUSIONS: The results of this study demonstrated that tennis players with scapular dyskinesia present a smaller subacromial space than control participants. Furthermore, when the shoulder was analysed dynamically, moving from neutral abduction to 60 degrees of elevation, the tennis players with scapular dyskinesia presented a greater reduction in the subacromial space compared with unaffected athletes.

Methylated bismuth, but not bismuth citrate or bismuth glutathione, induces cyto- and genotoxic effects in human cells in vitro.

Bismuth compounds are widely used in industrial processes and products. In medicine, bismuth salts have been applied in combination with antibiotics for the treatment of Helicobacter pylori infections, for the prevention of diarrhea, and in radioimmunotherapy. In the environment, bismuth ions can be biotransformed to the volatile bismuth compound trimethylbismuth (Me3Bi) by methanobacteria. Preliminary in-house studies have indicated that bismuth ions are methylated in the human colon by intestinal microflora following ingestion of bismuth-containing salts. Information concerning cyto- and genotoxicity of these biomethylated products is limited. In the present study, we investigated the cellular uptake of an organic bismuth compound [monomethylbismuth(III), MeBi(III)] and two other bismuth compounds [bismuth citrate (Bi-Cit) and bismuth glutathione (Bi-GS)] in human hepatocytes, lymphocytes, and erythrocytes using ICP-MS. We also analyzed the cyto- and genotoxic effects of these compounds to investigate their toxic potential. Our results show that the methylbismuth compound was better taken up by the cells than Bi-Cit and Bi-GS. All intracellularly detected bismuth compounds were located in the cytosol of the cells. MeBi(III) was best taken up by erythrocytes (36%), followed by lymphocytes (17%) and hepatocytes (0.04%). Erythrocytes and hepatocytes were more susceptible to MeBi(III) exposure than lymphocytes. Cytotoxic effects of MeBi(III) were detectable in erythrocytes at concentrations >4 microM, in hepatocytes at >130 microM, and in lymphocytes at >430 microM after 24 h of exposure. Cytotoxic effects for Bi-Cit and Bi-GS were much lower or not detectable in the used cell lines up to a tested concentration of 500 microM. Exposure of lymphocytes to MeBi(III) (250 microM for 1 h and 25 microM/50 microM for 24 h) resulted in significantly increased frequencies of chromosomal aberrations (CA) and sister chromatid exchanges (SCE), whereas Bi-Cit and Bi-GS induced neither CA nor SCE. Our study also showed an intracellular production of free radicals caused by MeBi(III) in hepatocytes but not in lymphocytes. These data suggest that biomethylation of bismuth ions by the intestinal microflora of the human colon leads to an increase in the toxicity of the primary bismuth salt.

[Massive hemorrhage following photodynamic therapy in exudative ARMD]. / Hémorragie maculaire massive après photothérapie dynamique pour dégénérescence maculaire liée à l'âge exsudative.

Photodynamic therapy (PDT) can prevent visual loss and the risk of hemorrhage in exudative ARMD. Nevertheless, it can sometimes complicate with massive hemorrhage. We report the case of a massive macular hemorrhage 4 days after a first treatment with dynamic phototherapy (PDT) with Visudyne for rapidly progressive (6 months) exudative AMD with occult neovessels in an 86-year-old female. The rationale for PDT was a rapidly progressive lesion with preserved visual acuity (20/40). Four days after injection, a massive submacular hemorrhage of 6 disc diameter developed, with a dramatic decrease in visual acuity. This hemorrhage recovered within 6 months, producing large, fibroglial, submacular scarring with changes on the retinal pigment epithelium. This case highlights the possible side effects of this treatment.

Reggies/flotillins regulate cytoskeletal remodeling during neuronal differentiation via CAP/ponsin and Rho GTPases.

The reggies/flotillins were discovered as proteins upregulated during axon regeneration. Here, we show that expression of a trans-negative reggie-1/flotillin-2 deletion mutant, R1EA, which interferes with oligomerization of the reggies/flotillins, inhibited insulin-like growth factor (IGF)-induced neurite outgrowth in N2a neuroblastoma cells and impaired in vitro differentiation of primary rat hippocampal neurons. Cells expressing R1EA formed only short and broad membrane protrusions often with abnormally large growth cones. R1EA expression strongly perturbed the balanced activation of the Rho-family GTPases Rac1 and cdc42. Furthermore, focal adhesion kinase (FAK) activity was also enhanced by R1EA expression, while other signaling pathways like ERK1/2, PKC or PKB signaling were unaffected. These severe signaling defects were caused by an impaired recruitment of the reggie/flotillin-associated adaptor molecule CAP/ponsin to focal contacts at the plasma membrane. Thus, the reggies/flotillins are crucial for coordinated assembly of signaling complexes regulating cytoskeletal remodeling.

Progesterone receptor variation and risk of ovarian cancer is limited to the invasive endometrioid subtype: results from the Ovarian Cancer Association Consortium pooled analysis.

There is evidence that progesterone plays a role in the aetiology of invasive epithelial ovarian cancer. Therefore, genes involved in pathways that regulate progesterone may be candidates for susceptibility to this disease. Previous studies have suggested that genetic variants in the progesterone receptor gene (PGR) may be associated with ovarian cancer risk, although results have been inconsistent. We have established an international consortium to pool resources and data from many ovarian cancer case-control studies in an effort to identify variants that influence risk. In this study, three PGR single nucleotide polymorphisms (SNPs), for which previous data have suggested they affect ovarian cancer risk, were examined. These were +331 C/T (rs10895068), PROGINS (rs1042838), and a 3' variant (rs608995). A total of 4788 ovarian cancer cases and 7614 controls from 12 case-control studies were included in this analysis. Unconditional logistic regression was used to model the association between each SNP and ovarian cancer risk and two-sided P-values are reported. Overall, risk of ovarian cancer was not associated with any of the three variants studied. However, in histopathological subtype analyses, we found a statistically significant association between risk of endometrioid ovarian cancer and the PROGINS allele (n=651, OR=1.17, 95% CI=1.01-1.36, P=0.036). We also observed borderline evidence of an association between risk of endometrioid ovarian cancer and the +331C/T variant (n=725 cases; OR=0.80, 95% CI 0.62-1.04, P=0.100). These data suggest that while these three variants in the PGR are not associated with ovarian cancer overall, the PROGINS variant may play a modest role in risk of endometrioid ovarian cancer.

[Measurement of the central corneal power after myopic LASIK]. / Evaluation der zentralen Hornhautbrechkraft nach myoper LASIK.

PURPOSE: Comparison of the central corneal refractive power before and after myopic LASIK using the Keratograph and the Pentacam. The Scheimpflug technique (Pentacam) enables the measurement of the corneal refractive power by examining the anterior and posterior corneal curvature. METHOD: The corneal refractive power of 59 eyes was examined before, 3 months and 6 months after myopic LASIK. The refractive power was measured at the corneal apex and at a distance of 2 and 4 mm. Statistical analysis was performed using the Wilcoxon signed rank test; a p value of 0.05 or less was considered statistically significant. RESULTS: At the corneal apex and at a distance of 2 mm the findings with the Keratograph showed a higher refractive power of up to 1.05 D. The differences were statistically significant at all times. At a distance of 4 mm from the corneal apex postoperatively there was no statistically significant difference. CONCLUSION: The results using the Pentacam system showed a lower corneal refractive power following myopic LASIK at all times. Its measuring principle compared to that of the Keratograph should be preferred when detecting changes of the refractive power of the central cornea after corneal refractive procedures.

The cyto- and genotoxicity of organotin compounds is dependent on the cellular uptake capability.

Organotin compounds have been widely used as stabilizers and anti-fouling agents with the result that they are ubiquitously distributed in the environment. Organotins accumulate in the food chain and potential effects on human health are disquieting. It is not known as yet whether cell surface adsorption or accumulation within the cell, or indeed both is a prerequisite for the toxicity of organotin compounds. In this study, the alkylated tin derivatives monomethyltin trichloride (MMT), dimethyltin dichloride (DMT), trimethyltin chloride (TMT) and tetramethyltin (TetraMT) were investigated for cyto- and genotoxic effects in CHO-9 cells in relation to the cellular uptake. To identify genotoxic effects, induction of micronuclei (MN), chromosome aberrations (CA) and sister chromatid exchanges (SCE) were analyzed and the nuclear division index (NDI) was calculated. The cellular uptake was assessed using ICP-MS analysis. The toxicity of the tin compounds was also evaluated after forced uptake by electroporation. Our results show that uptake of the organotin compounds was generally low but dose-dependent. Only weak genotoxic effects were observed after exposure of cells to DMT and TMT. MMT and TetraMT were negative in the test systems. After forced uptake by electroporation MMT, DMT and TMT induced significant DNA damage at non-cytotoxic concentrations. The results presented here indicate a considerable toxicological potential of some organotin species but demonstrate clearly that the toxicity is modulated by the cellular uptake capability.