["Blue eyes"-case report about the risks of cosmetic iris implants]. / "Blaue Augen" ­ Fallbericht über die Risiken von kosmetischen Irisimplantaten.

A 24-year-old Iranian woman presented to our department for routine eye control. She had had cosmetic iris implants (BrightOcular©) implanted 5 years before in a Tunisian eye clinic in order to change the color of her eyes. Despite subjective freedom of symptoms, a dramatically reduced corneal endothelial cell count was measured in the left eye. Therefore, surgical removal of the angle-supported cosmetic iris implants was necessary. Cosmetic iris implants are associated with sight-threatening complications-even years after their implantation. We report on a case of cosmetic iris implants inserted for alteration of eye color only, which gave rise to serious complications for our patient.

[Management of Radius-Maumenee syndrome : Treatment with deep sclerectomy, viscocanalostomy and collagen matrix implantation]. / Management des Radius-Maumenee-Syndroms : Therapie mit tiefer Sklerektomie, Viskokanalostomie und Kollagenmatriximplantation.

We describe the case of an 18-year-old female patient who presented with vasodilation of the episcleral vessels in both eyes. The dilated vessels were more prominent in the right eye and, furthermore, examination of the fundus oculi showed a glaucomatous excavation of the right optic disc. No underlying eye or systemic disease was found as the cause for the vasodilation, therefore, Radius-Maumenee syndrome (idiopathic dilated episcleral vessels with secondary open angle glaucoma) was diagnosed. Radius-Maumenee syndrome is a diagnosis by exclusion. If no underlying disease can be detected primary therapy of the glaucoma is required. Carotid cavernous fistulas as the most common cause for dilated episcleral vessels and elevated episcleral venous pressure should be ruled out. Due to the progression of the excavation and the pathologically elevated intraocular pressure in the right eye of our patient we decided to perform a deep sclerectomy in combination with viscocanalostomy and implantation of a collagen matrix. The operation and postoperative period were free from complications. Two months after the surgical procedure the right eye showed a normalized intraocular pressure of 7 mmHg but no morphological changes in terms of reduction of the vasodilation. In summary, deep sclerectomy in combination with viscocanalostomy and implantation of a collagen matrix showed good results in the reduction of intraocular eye pressure in Radius-Maumenee syndrome.

[Shock-induced anterior ischemic optic neuropathy from hemorrhagic anemia]. / Schockinduzierte anteriore ischämische Optikusneuropathie bei Blutungsanämie.

A 51-year-old diabetic and overweight male presented to our eye clinic with right-sided impairment of visual acuity and scotoma. A thorough work-up had been carried out at our institute 9 months prior to this event due to left-sided nonarteriitic anterior ischemic optic neuropathy (NAION). Despite the similarity of visual symptoms in the currently and previously affected eyes microcystic anemia (Hb 81 g/dl) associated with severe hemorrhoidal bleeding was diagnosed. The patient underwent surgical hemorrhoidectomy and received two red blood cell concentrates. Therefore, this article reports on an extraordinarily rare case of shock-induced anterior ischemic optic neuropathy (SIAION) caused by hemorrhoidal bleeding.

Thrombospondins in cancer.

The thrombospondins (TSPs) are a family of five proteins that are involved in the tissue remodeling that is associated with embryonic development, wound healing, synaptogenesis, and neoplasia. These proteins mediate the interaction of normal and neoplastic cells with the extracellular matrix and surrounding tissue. In the tumor microenvironment, TSP-1 has been shown to suppress tumor growth by inhibiting angiogenesis and by activating transforming growth factor beta. TSP-1 inhibits angiogenesis through direct effects on endothelial cell migration and survival, and through effects on vascular endothelial cell growth factor bioavailability. In addition, TSP-1 may affect tumor cell function through interaction with cell surface receptors and regulation of extracellular proteases. Whereas the role of TSP-1 in the tumor microenvironment is the best characterized, the other TSPs may have similar functions. (Part of a Multi-author Review).

Guanylyl cyclase is an ATP sensor coupling nitric oxide signaling to cell metabolism.

Defending cellular integrity against disturbances in intracellular concentrations of ATP ([ATP](i)) is predicated on coordinating the selection of substrates and their flux through metabolic pathways (metabolic signaling), ATP transfer from sites of production to utilization (energetic signaling), and the regulation of processes consuming energy (cell signaling). Whereas NO and its receptor, soluble guanylyl cyclase (sGC), are emerging as key mediators coordinating ATP supply and demand, mechanisms coupling this pathway with metabolic and energetic signaling remain undefined. Here, we demonstrate that sGC is a nucleotide sensor whose responsiveness to NO is regulated by [ATP](i). Indeed, ATP inhibits purified sGC with a K(i) predicting >60% inhibition of NO signaling in cells maintaining physiological [nucleotide](i). ATP inhibits sGC by interacting with a regulatory site that prefers ATP > GTP. Moreover, alterations in [ATP](i), by permeabilization and nucleotide clamping or inhibition of mitochondrial ATP synthase, regulate NO signaling by sGC. Thus, [ATP](i) serves as a "gain control" for NO signaling by sGC. At homeostatic [ATP](i), NO activation of sGC is repressed, whereas insults that reduce [ATP](i,) derepress sGC and amplify responses to NO. Hence, sGC forms a key synapse integrating metabolic, energetic, and cell signaling, wherein ATP is the transmitter, allosteric inhibition the coupling mechanism, and regulated accumulation of cGMP the response.

Bacterial enterotoxins are associated with resistance to colon cancer.

One half million patients suffer from colorectal cancer in industrialized nations, yet this disease exhibits a low incidence in under-developed countries. This geographic imbalance suggests an environmental contribution to the resistance of endemic populations to intestinal neoplasia. A common epidemiological characteristic of these colon cancer-spared regions is the prevalence of enterotoxigenic bacteria associated with diarrheal disease. Here, a bacterial heat-stable enterotoxin was demonstrated to suppress colon cancer cell proliferation by a guanylyl cyclase C-mediated signaling cascade. The heat-stable enterotoxin suppressed proliferation by increasing intracellular cGMP, an effect mimicked by the cell-permeant analog 8-br-cGMP. The antiproliferative effects of the enterotoxin and 8-br-cGMP were reversed by L-cis-diltiazem, a cyclic nucleotide-gated channel inhibitor, as well as by removal of extracellular Ca(2+), or chelation of intracellular Ca(2+). In fact, both the enterotoxin and 8-br-cGMP induced an L-cis-diltiazem-sensitive conductance, promoting Ca(2+) influx and inhibition of DNA synthesis in colon cancer cells. Induction of this previously unrecognized antiproliferative signaling pathway by bacterial enterotoxin could contribute to the resistance of endemic populations to intestinal neoplasia, and offers a paradigm for targeted prevention and therapy of primary and metastatic colorectal cancer.

Paraneoplastic pemphigus in children and adolescents.

BACKGROUND: Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous disease associated with specific B-cell lymphoproliferative neoplasms. There has been an increasing number of individual reports in the childhood and adolescent population. OBJECTIVES: To examine the clinical and immunopathological features of PNP occurring in children and adolescents. PATIENTS AND METHODS: We analysed the clinical and immunopathological findings of 14 patients under the age of 18 years with a confirmed diagnosis of PNP. Sera from all patients were analysed by indirect immunofluorescence (IF) and immunoprecipitation for plakin autoantibodies, immunoblotting for detection of plectin autoantibodies, and enzyme-linked immunosorbent assay (ELISA) for the detection of desmoglein (Dsg) 1 and Dsg3 autoantibodies. RESULTS: Severe oral mucositis was observed in all patients, and lichenoid cutaneous lesions in eight of 14 patients. The average age at presentation was 13 years. Striking findings included: pulmonary destruction leading to bronchiolitis obliterans in 10 patients, association with Castleman's disease in 12 patients, and a fatal outcome in 10 patients. The underlying neoplasm was occult in 10 patients. Histological findings include lichenoid and interface dermatitis with variable intraepithelial acantholysis. Deposition of IgG and C3 in the mouth and skin by direct IF was not found in some cases, but indirect IF detected IgG autoantibodies in all cases. Immunoprecipitation revealed IgG autoantibodies against desmoplakin I, envoplakin and periplakin in all cases, and against desmoplakin II and the 170-kDa antigen in 13 and 10 patients, respectively. Dsg3 and Dsg1 autoantibodies were present in 10 and three patients, respectively, and plectin autoantibodies in 13 patients. CONCLUSIONS: PNP in children and adolescents is most often a presenting sign of occult Castleman's disease. It presents with severe oral mucositis and cutaneous lichenoid lesions. Serum autoantibodies against plakin proteins were the most constant diagnostic markers. Pulmonary injury appears to account for the very high mortality rates observed.

Guanylyl cyclases and signaling by cyclic GMP.

Guanylyl cyclases are a family of enzymes that catalyze the conversion of GTP to cGMP. The family comprises both membrane-bound and soluble isoforms that are expressed in nearly all cell types. They are regulated by diverse extracellular agonists that include peptide hormones, bacterial toxins, and free radicals, as well as intracellular molecules, such as calcium and adenine nucleotides. Stimulation of guanylyl cyclases and the resultant accumulation of cGMP regulates complex signaling cascades through immediate downstream effectors, including cGMP-dependent protein kinases, cGMP-regulated phosphodiesterases, and cyclic nucleotide-gated ion channels. Guanylyl cyclases and cGMP-mediated signaling cascades play a central role in the regulation of diverse (patho)physiological processes, including vascular smooth muscle motility, intestinal fluid and electrolyte homeostasis, and retinal phototransduction. Topics addressed in this review include the structure and chromosomal localization of the genes for guanylyl cyclases, structure and function of the members of the guanylyl cyclase family, molecular mechanisms regulating enzymatic activity, and molecular sequences coupling ligand binding to catalytic activity. A brief overview is presented of the downstream events controlled by guanylyl cyclases, including the effectors that are regulated by cGMP and the role that guanylyl cyclases play in cell physiology and pathophysiology.