Bilateral Serous Retinal Detachment as a Complication of HELLP Syndrome.

HELLP syndrome is a pregnancy complication, putting at risk the life of mother and child, characterized by high blood pressure, elevated liver enzymes and low platelets. Serous retinal detachment is a rare complication of pregnancy and may be associated with HELLP syndrome. One of the most common symptoms is a decrease in visual acuity. A rare case of bilateral exudative retinal detachment associated with HELLP syndrome is described in a 38-year-old woman a few hours after delivery. Optical coherence tomography (OCT) showed an amount of subretinal fluid and macular edema. Use of systemic corticosteroids and careful management of blood pressure led to early resolution of subretinal fluid and a good recovery of vision. Her final best corrected visual acuity was 1 (decimal notation) in both eyes at 2 weeks after delivery. These types of cases are rarely reported and highlight the importance of increasing awareness of this pathology among ophthalmologists.

Impact of Mitochondrial Targeting Antibiotics on Mitochondrial Function and Proliferation of Cancer Cells.

Some marketed antibiotics can cause mitochondria dysfunction via inhibition of the mitochondrial translation process. There is great interest in exploiting such effects within a cancer setting. To enhance accumulation of antibiotics within the mitochondria of cancer cells, and therefore delivery of a greater potency payload, a mitochondrial targeting group in the form of a triphenylphosphonium (TPP) cation was appended via an alkyl chain length consisting of 7 to 11 carbons to the ribosomal antibiotics azithromycin and doxycycline. Using MDA-MB-231 cells, the effects of each subseries on mitochondrial translation, mitochondrial bioenergetics, and cell viability are described.

Oxidants induce a corticosteroid-insensitive phosphorylation of histone 3 at serine 10 in monocytes.

Oxidative stress enhances inflammation and reduces the effectiveness of corticosteroids, but the inflammatory signalling pathways induced by oxidants remain ill-defined. Phosphorylation of histone 3 at serine 10 (H3-Pser10) marks out a subset of inflammatory genes for transcription, several of which are induced in oxidant-associated inflammation. However, the influence of oxidants or of corticosteroids on this modification remains unknown. We assessed the regulation of H3-Pser10 by oxidants and lipopolysaccharide (LPS) in human blood monocytes and lung macrophages and the effectiveness of its abolition in controlling inflammatory gene expression in cells from asthmatic subjects compared to corticosteroids alone. Both oxidants and LPS promoted the induction of H3-Pser10 which was unaffected by corticosteroids. The induction of H3-Pser10 was mediated through p38α mitogen-activated protein kinase (MAPK) and IκB kinase 2 (IKK-2) signalling. Consequently, inhibitors of p38α MAPK or IKK-2 used in combination with dexamethasone were more effective at controlling inflammatory gene expression from monocytes and lung macrophages from asthmatic patients than the corticosteroid alone. Therefore, reduction of H3-Pser10 by inhibition of p38α MAPK or of IKK-2 may provide greater anti-inflammatory control than corticosteroids alone in oxidant-associated inflammation such as severe asthma.

MAPKAP kinase 2 blocks tristetraprolin-directed mRNA decay by inhibiting CAF1 deadenylase recruitment.

Tristetraprolin (TTP) directs its target AU-rich element (ARE)-containing mRNAs for degradation by promoting removal of the poly(A) tail. The p38 MAPK pathway regulates mRNA stability via the downstream kinase MAPK-activated protein kinase 2 (MAPKAP kinase 2 or MK2), which phosphorylates and prevents the mRNA-destabilizing function of TTP. We show that deadenylation of endogenous ARE-containing tumor necrosis factor mRNA is inhibited by p38 MAPK. To investigate whether phosphorylation of TTP by MK2 regulates TTP-directed deadenylation of ARE-containing mRNAs, we used a cell-free assay that reconstitutes the mechanism in vitro. We find that phosphorylation of Ser-52 and Ser-178 of TTP by MK2 results in inhibition of TTP-directed deadenylation of ARE-containing RNA. The use of 14-3-3 protein antagonists showed that regulation of TTP-directed deadenylation by MK2 is independent of 14-3-3 binding to TTP. To investigate the mechanism whereby TTP promotes deadenylation, it was necessary to identify the deadenylases involved. The carbon catabolite repressor protein (CCR)4.CCR4-associated factor (CAF)1 complex was identified as the major source of deadenylase activity in HeLa cells responsible for TTP-directed deadenylation. CAF1a and CAF1b were found to interact with TTP in an RNA-independent fashion. We find that MK2 phosphorylation reduces the ability of TTP to promote deadenylation by inhibiting the recruitment of CAF1 deadenylase in a mechanism that does not involve sequestration of TTP by 14-3-3. Cyclooxygenase-2 mRNA stability is increased in CAF1-depleted cells in which it is no longer p38 MAPK/MK2-regulated.

The p38 MAPK pathway inhibits tristetraprolin-directed decay of interleukin-10 and pro-inflammatory mediator mRNAs in murine macrophages.

p38 mitogen-activated protein kinase (MAPK) stabilises pro-inflammatory mediator mRNAs by inhibiting AU-rich element (ARE)-mediated decay. We show that in bone-marrow derived murine macrophages tristetraprolin (TTP) is necessary for the p38 MAPK-sensitive decay of several pro-inflammatory mRNAs, including cyclooxygenase-2 and the novel targets interleukin (IL)-6, and IL-1alpha. TTP(-/-) macrophages also strongly overexpress IL-10, an anti-inflammatory cytokine that constrains the production of the IL-6 despite its disregulation at the post-transcriptional level. TTP directly controls IL-10 mRNA stability, which is increased and insensitive to inhibition of p38 MAPK in TTP(-/-) macrophages. Furthermore, TTP enhances deadenylation of an IL-10 3'-untranslated region RNA in vitro.

Post-transcriptional gene regulation by MAP kinases via AU-rich elements.

Eukaryotic cells must continuously sense their environments, for example their attachment to extracellular matrix and proximity to other cells, differences in temperature or redox conditions, the presence of nutrients, growth factors, hormones, cytokines or pathogens. The information must then be integrated and an appropriate response initiated by modulating the cellular programme of gene expression. The mitogen-activated protein kinase (MAPK) signaling pathways play a critical role in this process. Decades of research have illuminated the many ways in which MAPKs regulate the synthesis of mRNA (transcription) via phosphorylation of transcription factors, cofactors, and other proteins. In recent years it has become increasingly clear that the control of mRNA destruction is equally important for cellular responses to extracellular cues, and is equally subject to regulation by MAPKs. This review will summarize our current understanding of post-transcriptional regulation of gene expression by the MAPKs and the proteins that are involved in this process.

[Refractive surgery--possibilities to maximize postoperative visual acuity]. / Chirurgia refractiva - modalitati de optimizare vizuala postoperatorie.

Laser refractive surgery has an ascendant evolution on the context of the progress in the medical field. The functional result can be negatively influenced by residual errors, irregular astigmatism or anisometropia, situations in which rigid gas permeable (RGP) contact lenses are a successful alternative in optimizing visual acuity. The paper presents the particularities and the protocol of RGP fitting, outlining the contribution of the corneal topography in the ocular pre and post-operative evaluation.

[Preliminary study about therapeutical contact lenses use]. / Studii preliminare asupra folosirii lentilelor de contact terapeutice.

THE AIM OF THE PAPER: The goal of the paper is to emphasize the advantages of the application of therapeutical contact lenses as compared to the eye patch. MATERIAL AND METHOD: There have been taken into study 42 patients-43 eyes, to whom we applied therapeutical contact lenses. RESULTS AND DEBATES: In the studied cases there have been taken into discussion the type of corneal diseases, the treatment prescribed, the period of time that the lenses have been worn and the possible complications. There have been prevailed herpetic keratopathies (12 cases), edemato-bullous keratopathies--aphakic and pseudophakic (12 cases), followed by recurrent corneal erosions (4 cases), full thickness corneal and corneoscleral lacerations (4 cases) and alkali chemical corneo-conjunctival burns of II-nd/III-rd degree and III-rd degree. CONCLUSIONS: 1. The wearing of therapeutical contact lens determined the improvement of the pain, of the eye discomfort and the corneal epithelium healing. 2. A therapeutical alternative clearly superior to the occlusive eye patch, the therapeutical contact lens limits the indications of tarsorrhaphy and conjunctival flap. 3. The therapeutical contact lens find their usefulness in a tectonic aim until the final surgical solution.