Notes

Link between XEN Gel Stent Implantation within the Inferonasal Quadrant right after Hit a brick wall Trabeculectomy.
Immunofluorescence allows the detection, visualization, and localization of proteins by using the ability of antibodies to firmly bind to specific antigens. Proteins must be accessible to thorough interaction with the specific antibodies. Different immune evasion mechanisms of parasites are directed to hamper or prevent access of antibodies to critical proteins or virulence factors. The blood fluke Schistosoma mansoni would not survive a day in the host blood capillaries if antibodies were able to readily bind to proteins located at the surface and mediate its attrition and demise by the complement system and/or the FcγR- or FcαR-bearing leukocytes. The worm surface is the area of parasite-host interaction and the route to critical nutrients, but is selectively permeable, allowing access of nutrient molecules but not host antibodies. Gentle procedures, which, however, are not commonly in use in vivo, are required to increase the permeability of the parasite outer membrane shield to just allow access of specific antibodies and identify and localize the proteins at the apical surface. Robust methods involving acetone, methanol, and Triton X-100 treatment lead to disintegration of the dual lipid bilayer cover with exposure of the proteins located in the tegument beneath. Internal proteins may not be accessed except following cryostat or paraffin sectioning. Accordingly, vaccine-induced specific antibodies to the apical surface or tegument proteins are unable to harm intact parasites. Specific antibodies to surface membrane proteins may only add to the action of administered or endo schistosomicides via acceleration of killing and interference with repair of severely and lightly impacted parasites, respectively. Therefore, careful immunofluorescent localization of S. mansoni proteins is important for devising the different control strategies against infection.Schistosomiasis is a chronic neglected tropical disease, highlighted by the presence of Schistosoma worms, which presents in advanced cases in approximately 80 countries, affecting almost 300 million people. The treatment is based on only one drug, praziquantel, a drug discovered in the 1970s that shows moderate efficacy against the adult parasite, but low efficacy against the larval stages of the parasite. Therefore, the use of only one drug has brought concerns and losses on drug-resistance cases, necessitating the development of new effective chemotherapeutic agents against Schistosoma species. One of the strategies that have been implemented in drug development is the computer-aided drug design (CADD), investigating the structural characteristics of the compounds and targets in order to understand their actions and biological activities through 3D virtual manipulation, as the QSAR applied to ligands and molecular docking applied to a respective biological target. These studies help to extract information and characteristics relevant to the activity, as well as to predict potential applications and activity. Therefore, this chapter will present the main validated biological targets of the genus Schistosoma, as thioredoxin glutathione reductase (TGR), histone deacetylases (HDAC 1, HDAC 8), dihydroorotate dehydrogenase, sirtuin protein and cathepsin L1, as well as reports of CADD in literature applied to the development of drugs against schistosomiasis, providing compounds with high pharmacological potential and high specificity.Praziquantel is a remarkably effective drug for the treatment of schistosomiasis. It has few side effects, some of which have been attributed to its inactive enantiomer. Few, if any, verified cases of drug resistance have been reported in a clinical setting. The preponderance of scientific evidence suggests that the drug works by dysregulating calcium homeostasis in the worm. Voltage-gated calcium channels have been proposed as the main pharmacological target of praziquantel, although no direct evidence of interaction with this protein is available. Here, the biochemical pharmacology of praziquantel is briefly reviewed and a hypothesis for its mechanism proposed. This hypothesis suggests that the drug works, in part, by disrupting an interaction between a voltage-gated calcium channel (SmCav1B) and an accessory protein, SmTAL1.Atrial fibrillation (AF) is the most common cardiac arrhythmia. Pharmacologic and non-pharmacologic rhythm control strategies impact on AF-related symptoms, while leaving largely unaffected the risk of stroke. Moreover, up to 20% of AF patients are asymptomatic during paroxysmal relapses of arrhythmia, thus underlying the need for early markers to identify at-risk patients and prevent cerebrovascular accidents. Indeed, non-invasive assessment of pre-clinical substrate changes that predispose to AF could provide early identification of at-risk patients and allow for tailored care paths. ECG-derived P wave analysis is a simple-to-use and inexpensive tool that has been successfully employed to detect AF-associated structural and functional atrial changes. Beyond standard electrocardiographic techniques, high resolution signal averaged electrocardiography (SAECG), by recording microvolt amplitude atrial signals, allows more accurate analysis of the P wave and possibly AF risk stratification. This review focuses on the evidence that support P wave analysis to assess AF substrates, predict arrhythmia relapses and guide rhythm-control interventions.The African clawed frog (Xenopus laevis) naturally tolerates severe dehydration using biochemical adaptation, one of which is the elevation of antioxidant defenses during whole-body dehydration. The present study investigated the role and regulation of a pathway known to regulate oxidative stress response, the Akt-FoxO signaling pathway, in clawed frog skeletal muscle, responding to medium (15%) and high (30%) dehydration. Protein levels of total and phosphorylated Akt, FoxO1, and FoxO3 were assessed via immunoblotting, in addition to the levels of the E3 ubiquitin ligase known to be associated with muscle atrophy, MAFbx. Akt activity/phosphorylation in addition to its total protein levels were decreased in the skeletal muscle during dehydration, and this corresponded with decreases in the relative phosphorylation of FoxO1 and FoxO3 as well on several residues. Akt is an inhibitor of FoxO1 and FoxO3 activity via phosphorylation, suggesting that FoxO activities were increased during dehydration stress. Furthermore, MAFbx showed decreased protein expression during high dehydration as well, suggesting that the clawed frog may exhibit some natural resistance to skeletal muscle atrophy during severe dehydration conditions. In addition to identifying that the suppression of Akt could lead to an activation of FoxO transcription factors in X. laevis during dehydration, these investigations suggest that X. laevis dehydration may implicate FoxO1 and FoxO3 in controlling skeletal muscle atrophy in X. laevis exposed to dehydration. This study implicates the Akt signaling pathway, its regulation of FoxO transcription factors, and FoxO-controlled targets, in stress adaptation against dehydration.Background and objective Krüppel-like factors (KLFs) are transcription factors with the ability to mediate cross-talk with signaling pathways involved in cell proliferation control, apoptosis, migration, and differentiation. They also appear to influence steroid hormone signaling through transcriptional networks involving steroid hormone receptors and members of the nuclear receptor family of transcription factors. Our study aims to evaluate the potential prognostic role of KLF5, KLF9, and KLF11 in endometrial cancer, and their correlation with hormonal receptor status and cellular proliferation. Materials and methods Retrospective observational study on cases of endometrioid endometrial adenocarcinoma collected in the period January 2000-December 2011 at the University of Udine. Formalin-fixed, paraffin-embedded tissue samples were all submitted to tissue microarray immunohistochemical study. A survival analysis was performed. Results One hundred forty seven patients were included in the study with a mean age at surgery of 65.6 years (±10.2). 80.3% of endometrial malignancies were classified as stage FIGO I (118/147). Radiation therapy and chemotherapy were administered in 62.3% (91/146) and 6.2% (9/145) of patients respectively. Five-year overall survival and disease-free survival resulted 85.4% (95% CI, 79.8-91.4%) and 79.4% (95% CI, 73.0-86.4%) respectively. A high Ki-67, cytoplasmatic KLF5 (HR 4.72, CI.95 1.61-13.89, p less then 0.05), and nuclear KLF11 (HR 3.04, CI.95 0.99-9.36, p = 0.053) scores correlated with a shorter overall survival. In addition, a high nuclear KLF11 (HR 2.59, CI.95 1.13-5.95, p less then 0.05) score correlated with a shorter disease-free survival. Conclusions In patients affected by endometrioid endometrial carcinoma, higher staining levels of KLF5 and KLF11 correlated with a poorer prognosis. However, further studies are required in order to better clarify the role of KLFs in the natural history of endometrial cancer.Objective Implication of the tumor size on oncological and functional outcomes of craniopharyngioma is inconsistently reported. The aim of this study is to assess the postoperative outcome of giant craniopharyngiomas (> 4 cm in diameter) and to elucidate the impact of tumor size on various outcome parameters and survival. Material and methods Forty-four patients (children aged ≤ 18 years 25; adults 16) with giant craniopharyngioma, operated between January 2001 and December 2015, were included in this study. Various outcomes, progression-free survival (PFS) and overall survival (OS) were calculated. Results Gross total resection (GTR) was achieved in 17 (39%) and subtotal resection (STR) in 27 (61%) patients. Eleven patients (25%) received radiotherapy (RT) after STR. Postoperatively, new cranial nerve and motor deficits were noted in 12 (27%) and 9 (20%) patients, respectively. Tumor recurrence following GTR and STR without adjuvant RT was diagnosed in 3 (17%), and 5 (38%) patients, respectively. Following S with giant tumor are comparable to non-giant tumors.Purpose Pegvisomant (PEG) is an effective therapy for acromegaly. Its safety in women seeking fertility and during pregnancy has been scarcely reported. Methods A retrospective chart review was performed in three patients with acromegaly who received PEG while attempting to conceive. Published studies regarding this topic were analyzed. Results Four pregnancies in three women with acromegaly are reported. In the first patient, PEG was withdrawn three days before embryo transfer in her first pregnancy and 2 weeks prior to transfer in the second pregnancy. Each transfer resulted in a healthy full-term newborn. In the second and third patients, PEG was withdrawn at diagnosis of pregnancy. No fetal complications occurred during gestations which resulted in three full-term newborns (one single and one twin pregnancy). No abnormalities in development were found in the five live births described. Few cases of pregnancies in women exposed to PEG have been reported and therefore safety cannot be clearly established. In this series, all four pregnancies had good outcomes with discontinuation of the drug before or at first knowledge of conception. Domatinostat inhibitor A review of the literature reveals no evident drug-related abnormalities in the offspring, even in the few women with continued use of PEG throughout pregnancy. Conclusion Preconception therapy with PEG resulted in successful fertility outcomes. Although few cases have been reported, these four pregnancies with PEG use prior to or at the time of conception were not associated with significant maternal or fetal complications. More studies are needed to establish the safety of PEG preconception.
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