[Recurrent DMEK failure]. / Rezidivierendes DMEK-Versagen.

We report a Patient with Fuchs dystrophy who underwent three Descemet Membrane Endothelial Keratoplasties (DMEK) caused by recurrent graft failure with raise in intraocular pressure and cystoid macular edema. At the third DMEK, herpes was detected in the anterior chamber tap and an adequate therapy was initiated. At the 6 months follow-up the cornea remained clear, visual acuity was 0.8, intraocular pressure was within normal range and macular edema regressed completely. Either a latent Herpes simplex Virus (HSV) infection of the patient was reactivated or an infected donor lamella was transplanted with donor-to-host-to-donor ping-pong transmission.

[Reliability of corneal tomography after implantation of intracorneal ring segments for keratoconus]. / Reliabilität der Hornhauttomographie nach Implantation von intrakornealen Ringsegmenten bei Keratokonus.

BACKGROUND AND OBJECTIVE: Intracorneal ring segments (ICRS) are believed to stop the progression of keratoconus (KC). This statement on progression, however, requires knowledge about measurement reproducibility. The purpose of this study was to compare the reproducibility of tomographic parameters in eyes with KC after femtosecond laser-assisted implantation of INTACS (fs-INTACS) using two different devices and to determine which is more reliable for the follow-up of these patients. PATIENTS AND METHODS: In this study 19 KC eyes were included and repeatedly examined 5 times with the Scheimpflug topography Pentacam HR and the Casia 2 optical coherence tomography (VA-OCT) devices. Outcome measures included the reproducibility and comparability of measurements between the two devices of (1) keratometric refractive power of the anterior cornea and (2) posterior cornea, (3) maximum keratometric refractive power, (4) central corneal thickness and (5) corneal thickness at the thinnest site. RESULTS: The mean differences (Pentacam minus Casia 2) of (1), (2), (3), (4) and (5) were 0.67 dpt, 0.41 dpt, 3.4 dpt, 1.5 µm and 11.8 µm, respectively. The mean SDs of the 5 repeat measurements for (1), (2), (3), (4) and (5) were 0.20 dpt/0.20 dpt, 0.10 dpt/0.07 dpt, 0.75 dpt/0.5 dpt, 6.5 µm/2.4 µm (p = 0.007) and 7.3 µm/1.9 µm (p = 0.001) for Pentacam and Casia 2, respectively. Cronbach's alpha was better than 0.98 for both devices and all parameters. CONCLUSION: Both Casia 2 and Pentacam enable a reliable assessment of the corneal refractive power in KC after fs-INTACS implantation; however, the reproducibility was significantly better with Casia 2 only for the measurement of corneal thickness. The Pentacam showed significantly higher values for the mean anterior and posterior corneal refractive power and measured significantly thicker at the thinnest point of the cornea compared to Casia 2.

Oral manifestations of inflammatory bowel disease.

Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, have important extraintestinal manifestations, notably in the oral cavity. These oral manifestations can constitute important clinical clues in the diagnosis and management of IBD, and include changes at the immune and bacterial levels. Aphthous ulcers, pyostomatitis vegetans, cobblestoning and gingivitis are important oral findings frequently observed in IBD patients. Their presentations vary considerably and might be well diagnosed and distinguished from other oral lesions. Infections, drug side effects, deficiencies in some nutrients and many other diseases involved with oral manifestations should also be taken into account. This article discusses the most recent findings on the oral manifestations of IBD with a focus on bacterial modulations and immune changes. It also includes an overview on options for management of the oral lesions of IBD.

Does EBV alter the pathogenesis of malaria?

Plasmodium falciparum infections have been implicated in immune deficiencies resulting in ineffective control of Epstein-Barr virus, thereby increasing the risk of endemic Burkitt lymphoma in children. However, the impact of Epstein-Barr virus infections on the development of immunity to P. falciparum has not been studied in depth. In this review, we examine novel findings from animal co-infection models and human immuno-epidemiologic studies to speculate on the impact of acute gammaherpesvirus co-infection on malarial disease severity. Children are often concurrently or sequentially infected with multiple pathogens, and this has implications for understanding the development of protective immunity as well as in the evaluation of vaccine efficacy.

'Desperate house genes': the dramatic example of hypoxia.

BACKGROUND: Microenvironmental conditions in normal or tumour tissues and cell lines may interfere on further biological analysis. To evaluate transcript variations carefully, it is common to use stable housekeeping genes (HKG) to normalise quantitative microarrays or real-time polymerase chain reaction results. However, recent studies argue that HKG fluctuate according to tissues and treatments. So, as an example of HKG variation under an array of conditions that are common in the cancer field, we evaluate whether hypoxia could have an impact on HKG expression. METHODS: Expression of 10 commonly used HKG was measured on four cell lines treated with four oxygen concentrations (from 1 to 20%). RESULTS: Large variations of HKG transcripts were observed in hypoxic conditions and differ along with the cell line and the oxygen concentration. To elect the most stable HKG, we compared the three statistical means based either on PCR cycle threshold coefficient of variation calculation or two specifically dedicated software. Nevertheless, the best HKG dramatically differs according to the statistical method used. Moreover, using, as a reference, absolute quantification of a target gene (here the proteinase activating receptor gene 1 (PAR1) gene), we show that the conclusions raised about PAR1 variation in hypoxia can totally diverge according to the selected HKG used for normalisation. CONCLUSION: The choice of a valid HKG will determine the relevance of the results that will be further interpreted, and so it should be seriously considered. The results of our study confirm unambiguously that HKG variations must be precisely and systematically determined before any experiment for each situation, to obtain reliable normalised results in the experimental setting that has been designed. Indeed, such assay design, functional for all in vitro systems, should be carefully evaluated before any extension to other experimental models including in vivo ones.

Antiobesity and antidiabetic effects of biotransformed blueberry juice in KKA(y) mice.

AIM: Biotransformation of blueberry juice by the Serratia vaccinii bacterium gave rise to adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and glucose uptake in muscle cells and adipocytes, but inhibited adipogenesis. This study investigated the antiobesity and antidiabetic potential of biotransformed blueberry juice (BJ) in KKA(y) mice, rodent model of leptin resistance. METHODS: BJ was incorporated in drinking water of KKA(y) mice. Parameters of body weight, food intake, plasma glucose, insulin, leptin, and adiponectin were measured. Before and after therapy, animals were subjected to an oral glucose tolerance test. At the end of treatment, liver, muscle, kidney, epididymal fat pad, abdominal fat pad, and dorsal fat pad were collected and weighed. RESULTS: Incorporating BJ in drinking water protected young KKA(y) mice from hyperphagia and significantly reduced their weight gain. Moreover, BJ protected young KKA(y) mice against the development of glucose intolerance and diabetes mellitus. Chronic BJ administration in obese and diabetic KKA(y) mice reduced food intake and body weight. This effect could not fully explain the associated antidiabetic effect because BJ-treated mice still showed lower blood glucose level when compared with pair-fed controls. The adipokines pathway also seems to be involved because BJ significantly increased adiponectin levels in obese mice. CONCLUSIONS: This study shows that BJ decreases hyperglycemia in diabetic mice, at least in part by reversing adiponectin levels. BJ also protects young pre-diabetic mice from developing obesity and diabetes. Thus, BJ may represent a novel complementary therapy and a source of novel therapeutic agents against diabetes mellitus.

Study of immune cells involved in the antitumor effect of kefir in a murine breast cancer model.

Administration of kefir and a kefir cell-free fraction (KF) to mice injected with breast tumor cells produced, locally in the mammary gland, different profiles of cells secreting cytokines. Here, the immune cell populations in mammary glands affected by the cyclic consumption of kefir or KF for 2 or 7 d were evaluated using a breast tumor model. Apoptosis was also assayed as another mechanism involved in tumor growth delay. The rate development of tumor cells, IgA(+) cells, and CD4+ and CD8+ T lymphocytes was monitored in mammary gland tissues. The number of Bcl-2(+) cells in the mammary gland was compared with the apoptosis observed in the tumor. Two-day cyclical administration of both products delayed tumor growth and increased the number of IgA(+) cells in the mammary gland. Changes in the balance between CD4+ and CD8+ cells in the mammary gland were observed in mice from the group fed KF cyclically for 2 d, such that the number of CD4+ cells increased when the number of CD8+ cells remained constant. Mice that received 2-d cyclic administration of KF showed significant increases in the number of apoptotic cells and decreases in Bcl-2(+) cells in the mammary gland, compared with the tumor control group. The present study allows a better understanding of the mechanisms (immune and nonimmune) involved in the antitumor effect observed in mice administered kefir or KF. The importance of nonmicrobial components released during milk fermentation to obtain the beneficial antitumor effects is also reported.

Study of cytokines involved in the prevention of a murine experimental breast cancer by kefir.

Previous studies have shown that compounds released during milk fermentation by Lactobacillus helveticus are implicated in the antitumour effect of this product. Here the effects of the consumption, during 2 or 7 days, of kefir or kefir cell-free fraction (KF) on the systemic and local immune responses in mammary glands and tumours using a murine hormone-dependent breast cancer model were studied. In the tumour control group, mice did not receive these products. At the end of the feeding period, mice were injected subcutaneously with tumour cells in the mammary gland. Four days post-injection, they received kefir or KF on a cyclical basis. Rate of tumour development, cytokines in serum; mammary gland tissue, and tumour isolated cells were monitored. Two-day cyclical administration of both products delayed tumour growth. Both kefir and KF increased IL-10 in serum and decreased IL-6(+) cells (cytokine involved in oestrogen synthesis) in mammary glands. Two-day cyclical administration of KF increased IL-10(+) cells in mammary glands and in tumours and decreased IL-6(+) cells in tumour. This study demonstrated the modulatory capacity of KF on the immune response in mammary glands and tumours and the importance of the administration period to obtain this effect.

Immunomodulating effects of peptidic fractions issued from milk fermented with Lactobacillus helveticus.

The effect of peptides released during the fermentation of milk on the humoral immune system and on fibrosarcoma growth was studied. Lactobacillus helveticus was able to release peptidic compounds during milk fermentation due to its high proteolytic activity, as was shown by the degree of proteolysis and size-exclusion HPLC elution profiles. Three fractions of these compounds were separated and fed to mice during different periods (2, 5, and 7 d). The humoral immune response was assessed by following the number of IgA-secreting cells, and the antitumor activity was monitored by studying the regression of subcutaneously implanted fibrosarcomas. Feeding during 2 and 7 d with the medium-sized fraction (Fraction II) significantly increased the IgA-producing cells in the intestines, whereas feeding with the large compound fraction (Fraction I) during 5 d and the small compound fraction (Fraction III) during all three feeding periods provided similar increases. A double dose of Fraction II showed the highest IgA-producing cell count. The increase by Fraction III was shown to be caused by the presence of L-Tryptophan. Fraction II significantly decreased the size of fibrosarcoma when previously fed during 7 d, and feeding with Fraction I during 5 d decreased significantly its size after 35 d of growth. Although the mechanisms by which lactic acid bacteria enhance the immune system are not clear, this study clearly shows that bioactive compounds released in fermented milks contribute to the immunoenhancing and antitumor properties of these products. The release of bioactive peptides by lactic acid bacteria can have important implications on the modulation of the cellular immune response.

Immunomodulating effects of milks fermented by Lactobacillus helveticus and its non-proteolytic variant.

The effect of milks fermented by Lactobacillus helveticus and its non-proteolytic variant on mucosal and tumoral immunity was studied. Milks fermented by Lb. helveticus wild type or its non-proteolytic variant were administered orally to mice for different periods (3, 5 and 7 d). The immune response was assessed by analysing the activity of the peritoneal macrophages, the number of cells secreting IgA associated with the gut-associated lymphoid tissue and with the bronchial-associated lymphoid tissue. The number of cells was determined by direct immunofluorescence. The antitumour activity was monitored by studying the regression of the subcutaneously implanted fibrosarcomas. After 3 d feeding of milk fermented by Lb. helveticus wild type, the number of sIgA increased significantly at both the intestinal and bronchial levels, indicating that a cellular migration had occurred. This effect was not noticeable when milk fermented by Lb. helveticus Protease (-) was orally administered. Both fermented milks (wild type or its variant) exhibited an effect on the activity of the peritoneal macrophages, which might be indirectly correlated to the regression of the fibrosarcoma. Although the mechanism by which the lactic acid bacteria enhance the immune system is not clear, this study clearly suggests that the bioactive compounds released during milk fermentation might contribute to the immunoenhancing properties of these products. By releasing biopeptide, lactic acid bacteria have important implications in modulation of the host's immune response, more specifically its cellular immune response.

Antimutagenic effects of milk fermented by Lactobacillus helveticus L89 and a protease-deficient derivative.

The antimutagenic effects of whey, acetone extracts, and protein fractions isolated from milk that had been fermented by Lactobacillus helveticus L89 were investigated using the mutagen 4-nitroquinoline-N'-oxide in the Ames test (Salmonella typhimurium TA 100). Fermented milk significantly inhibited mutagenesis induced by 4-nitroquinoline-N'-oxide. However, milk fermented by a nonproteolytic variant of the same strain showed no inhibitory effects. Results were similar for the whey fractions and acetone extracts of the fermented milks. After fermentation, milk proteins were fractionated by size-exclusion HPLC and were tested for antimutagenicity. The fraction showing the greatest activity was further analyzed by reverse-phase HPLC. Our results indicate that antimutagenic compounds are produced in milk during fermentation by L. helveticus, and the release of peptides is one possible contributing mechanism.

The effect of milk fermentation by Lactobacillus helveticus on the release of peptides during in vitro digestion.

This study evaluated the effect of protein hydrolysis by lactic acid bacteria during milk fermentation on the release of amino acids and peptides duing subsequently simulated peptic and pancreatic digestion. After digestion with trypsin, we compared the elution patterns of proteins and peptides obtained from unfermented milk and from milk fermented by Lactobacillus helveticus under pH control, using HPLC gel filtration and reverse-phase HPLC. The results indicate that milk fermentation affects the release of some amino acids during simulated gastrointestinal digestion and has a major impact on the modification of protein elution profiles obtained after digestion with trypsin. We conclude that proteolysis during fermentation may lead to the formation of novel peptides during gastrointestinal digestion.