Epigenetic therapy of lymphoma using histone deacetylase inhibitors

In this study, we reviewed epigenetic therapy of lymphomas using histone deacetylase inhibitors (HDACi), a promising new class of antineoplastic agents. Epigenetic therapy, a new therapeutic concept, consists of the use of HDACi and or DNA methyltransferase inhibitors (DNMTi). We conducted a comprehensive review of the literature for antitumour activity of HDACi and its mechanism of action. HDACi modify the expression of several genes related to cancer development, which can result in antineoplastic activity. To elucidate the benefits of HDACi in lymphoma treatment, we discuss the crucial interplay between BCL6, p53 and STAT3. Activated B-cell (ABC) diffuse large cell lymphoma (DLCL) is increasingly being recognised as an unfavourable and frequently therapy-refractory lymphoma. We discuss the fundamental causative role of the STAT3 oncogene in ABC type DLCL. STAT3 can be effectively suppressed by several HDACi, a promising treatment for this difficult subtype of DLCL. On the other hand, various HDACi can repress the germinal-centre B Cell (GCB) type DLCL by virtue of their inhibition of the BCL6 oncogene, usually expressed in this particular subtype. We summarise the results of recent clinical trials with HDACi such as romidepsin, panobinostat, MGCD-0103, entinostat, curcumin, JAK2 inhibitor TG101348, and valproic acid that have shown preliminary activity in recurrent and refractory lymphomas. The unique mechanism of action of HDACi makes them very attractive agents to pursue in combination. Several ongoing trials are already exploring HDACi combinations in various types of cancers. Their role in front-line management remains to be determined (AU)

Degradation of phenol by mechanical activation of a rutile catalyst.

In the present paper a novel mechanochemical process for the elimination of organic pollutants dissolved in water is proposed. In this regard, phenol aqueous solutions (100mgL(-1)) were ball-milled for 0, 12, 18, 24, 36, 48, and 72h with and without a well-characterized (XRD, SEM, and N(2) Adsorption), rutile powder catalyst and the reaction products analyzed with UV and GC/MS. It was found that when the catalyst was not included in the process, phenol was not affected, but when it was included, phenol was decomposed. The catalyst itself did not change and the reaction follows a pseudo-first-order kinetics. Besides, intermediates which are characteristic of the ()OH radical mechanism were found in the reaction products. Then, a mechanism similar to those accepted for other advanced oxidation processes was proposed. The value measured for the pseudo-first-order reaction constant was very low, indicating that the reported process is inefficient. Nevertheless, this problem could be solved by applying catalysts consisting of particles with smaller diameters.

Effect of flumazenil on electroencephalographic patterns induced by midazolam.

BACKGROUND: Flumazenil is a competitive benzodiazepine receptor antagonist, reverts the sedation effects of benzodiazepines and its effect on electroencephalographic (EEG) patterns is controversial. The purpose of this study was to describe flumazenil's effect on EEG patterns of patients undergoing conscious sedation. METHODS: Ten voluntary patients, aged 16-23, at elective oral surgery had conscious sedation with midazolam and local anesthesia. After the procedure, sedation was reversed with flumazenil. Each patient had 4 EEGs of 4 minutes each: baseline, 5 minutes after midazolam, prior to flumazenil, and 8 minutes after flumazenil. A clinical neurophysiologist interpreted EEGs blinded to time. RESULTS: Eight patients had an awake and 2 had an awake and drowsy normal EEG. After midazolam all developed a diffuse beta wave and alpha wave attenuation or dropout. Prior to flumazenil 7 presented diffuse beta and scattered theta waves, and 3 an awake pattern (procedure required > 30 minutes). After flumazenil, reversal of beta and theta waves and appearance of alpha waves was noted; no changes occurred when procedure lasted more than 30 minutes. One patient presented with diffuse theta waves, 6 Hz. CONCLUSIONS: Flumazenil reverts midazolam EEG changes if administered < 30 minutes after midazolam administration, midazolam-induced EEG changes revert spontaneously after 30 minutes, and flumazenil may precipitate theta activity.

Exit-site infection prevention and treatment protocol.

Infections are universally known as one of the main causes of drop-out in peritoneal dialysis. Exit-site infections are often a problem, as they are difficult to treat, tend to become chronic and may lead to the development of continuity peritonitis, resulting in the need for removal of the peritoneal catheter. The purpose of this paper is to describe the application of an exit-site infection prevention and treatment protocol.

Association between diuretic use, clinical response, and death in acute heart failure.

Because the impact of diuretic use on mortality in acute congestive heart failure (CHF) is not known, we examined the association between drug use, fluid balance, and death among 1,150 patients hospitalized for evaluation and treatment of CHF. After adjusting for other relevant intergroup differences, we observed that less net weight loss and a greater number of intravenous drug doses retained significant predictive value for death, suggesting that more frequent diuretic dosing or diuretic resistance may be related to mortality in acute CHF.

APD: selection criteria and training methods.

The growing use of automated night-time dialysis (APD) in peritoneal dialysis over the last few years shows that this method represents a valid alternative to continuous ambulatory peritoneal dialysis (CAPD). APD unquestionably offers a wide range of treatments which are able to cover the diverse dialytic needs of patients from both clinical and social points of view.

Patients' group experiences.

In 11 years of experience with dialysis, we have tried to supply a kind of treatment in our center that takes the patient's physical, psychological, and social needs into account. We have been able to observe how important it is to share the common problems connected with a chronic illness in order to make them appear less dramatic. This led to the idea of organizing a group holiday in which the patients and their families would be able to spend some time together. As a result of this positive experience, we decided to organize group encounters in which all the problems could be freely discussed. The group is open to all the patients on dialysis or who have undergone transplants and their families. The group, which has been meeting once every 3 weeks for the last 2 years, is coordinated by a psychologist. This has proved to be important both for the operators, who have been able to expand their own knowledge, and for the patients and their families for whom these gatherings represent a way of helping themselves face up to and accept the limits imposed by chronic illness.

Fat emulsion effects on prothrombin time in warfarin anticoagulated patients: an in vitro study.

The effect of lipid emulsions on prothrombin time in blood from anticoagulated patients was determined. Blood samples were obtained from 23 patients therapeutically anticoagulated with warfarin (prothrombin time 1.3-2.0 x control). Varying amounts of an intravenous lipid emulsion (Intra-lipid) were added to the blood to simulate concentrations seen in vivo with a constant lipid infusion. The prothrombin time was measured on the plasma from these samples and compared to the prothrombin time of the plasma samples without lipid. The mean decrease in prothrombin times were: 0.29 sec at 50 micrograms/ml, 0.23 sec at 100 micrograms/ml, and 0.29 sec at 200 micrograms/ml. All concentrations showed a statistically significant decrease (p less than 0.05) when compared to the control by the Scheffe test. Lipid emulsions appear to decrease the prothrombin times in anti-coagulated patients. The differences however, were small and not of clinical significance at the concentrations tested.

Possible relationship between pervasive developmental disorders and platelet monoamine oxidase activity.

1. The present study was undertaken to determine if the platelet monoamine oxidase (MAO) activity of children with childhood-onset Pervasive Developmental Disorders (PDD), atypical PDD and autistic children differs from MAO of normal children of the same age. 2. The kinetic parameters of MAO activity (Km and Vmax for kynuramine as substrate in 100 mM sodium phosphate buffer, pH 7.4 at 37 degrees C) were determined for platelets from autistic (N = 6), childhood onset PDD (N = 6) and atypical PDD (N = 6) children and 14 controls aged 6-10 years. 3. PDD children had significantly lower Km (4.41 +/- 0.26 vs 5.30 +/- 0.23 microM) and Vmax (16.77 +/- 1.56 vs 22.15 +/- 2.16 nmol h-1 mg protein-1) than control children. The reduction in Vmax was demonstrable in MAO activity measured with 100 microM substrate (14.93 +/- 1.13 vs 20.96 +/- 2.10 nmol h-1 mg-1). 4. These data show that childhood-onset PDD patients, in which the syndrome was complete, presented the lowest levels of platelet MAO activity.