Etanercept as a possible trigger of fatal pulmonary fibrosis

Pulmonary fibrosis can be caused by external agents, including certain drugs. For some time now, tumor necrosis factor antagonists such as etanercept have been used to treat certain autoimmune diseases. Fibrosis caused by medication responds to withdrawal of the drug and treatment with corticosteroids. Very rarely, fibrosis is irreversible. We present the case of a patient who developed pulmonary fibrosis after initiating treatment with etanercept. The clinical course was fulminant despite withdrawal of the drug and high doses of corticosteroids.     

Progress in cardiac pacing

This review summarizes recent scientific developments in ambulatory monitoring and its legal implications in appropriately selected patients. It also considers how new cardiac pacing devices can be used in the clinical monitoring of atrial fibrillation, sleep apnea and, in transplant patients, heart failure and transplant rejection. In addition, the system of accreditation for cardiac pacing services in Spain is outlined, with a focus on process development and quality indicators. Finally, the scientific articles on cardiac pacing that made the greatest impact in 2007 are summarized.     

rTMS strategies for the study and treatment of schizophrenia: a review

Transcranial magnetic stimulation (TMS) and repetitive TMS (rTMS) have been used increasingly over the past few years to study both the pathophysiology of schizophrenia as well as the utility of focal neuromodulation as a novel treatment for schizophrenia. rTMS treatment studies to date have explored its effect on both positive and negative symptoms by targeting cortical regions thought to underlie these symptom clusters. Studies on auditory hallucinations have been largely positive, while efficacy for negative symptoms is equivocal. A better understanding of the functional abnormalities that accompany symptoms may facilitate the development of rTMS as a treatment modality. Furthermore, schizophrenia patients appear to have abnormal cortical inhibition, consistent with GABA and dopamine abnormalities in schizophrenia. The effect of TMS on GABA and dopamine neurotransmission has not been clearly delineated. Given the variability in cortical response to rTMS in schizophrenia, methods to optimize dosage are essential. Consideration of these factors among others may broaden the scope of utility of TMS for schizophrenia as well as enhance its efficacy.     

Development and validation of a reverse-phase liquid chromatographic method for the assay of lidocaine hydrochloride in alginate-Gantrez microspheres

A simple, fast and reliable reverse-phase high-performance liquid chromatographic (HPLC) method was developed for the assay of lidocaine hydrochloride (LH) in Gantrez-alginate microspheres. Separation was achieved in a LiChrospher C18 column, using a mobile phase consisting of acetonitrile:ammonium acetate (0.0257 M) adjusted to pH 4.85 with acetic acid, in the ratio 70:30 (v/v) and a flow rate of 0.6 mL/min. The detection was made with a diode array detector measuring at the maximum for the compound. The validation study demonstrated that the method was precise, accurate and linear over the concentration range of analysis with a limit of detection of 0.001 mg/mL. The limit of quantification was 0.002 mg/mL. Linear regression analysis in the range of 0.8-2.4 mg/mL gave correlation coefficients higher than 0.995. The method developed was applied to the analysis of lidocaine in microsphere samples in order to evaluate in next papers, the encapsulation efficiency of different formulations.     

Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors

The work provides a new model for the prediction of the MAO-A and -B inhibitor activity by the use of combined complex networks and QSAR methodologies. On the basis of the obtained model, we prepared and assayed 33 coumarin derivatives, and the theoretical prediction was compared with the experimental activity data. The model correctly predicted 27 compounds, and most of the active derivatives showed IC 50 values in the muM-nM range against both the MAO-A and MAO-B isoforms. Compound 14 shows the same MAO-A inhibitory activity (IC 50 = 7.2 nM), as clorgyline used as a reference inhibitor and has the highest MAO-A specificity (1000-fold higher compared to MAO-B). On the other hand, compounds 24 (IC 50 = 1.2 nM) and 28 (IC 50 = 1.5 nM) show higher activity than selegiline (IC 50 = 19.6 nM) and high MAO-B selectivity with 100-fold and 1600-fold inhibition levels, with respect to the MAO-A isoform.     

Melatonin modulates the cadmium-induced expression of MT-2 and MT-1 metallothioneins in three lines of human tumor cells (MCF-7, MDA-MB-231 and HeLa)

Cadmium (Cd) is a human carcinogen present in tobacco smoke and contaminated industrial soils. Metallothioneins (MTs) are intracellular proteins involved in protecting against Cd. The toxic effects of Cd can be modified by compounds able to modulate MTs synthesis. Melatonin has oncostatic properties and has also been shown to counteract the toxic effects of Cd. In this study we examine the possible role of melatonin in Cd-induced expression of several MT isoforms (MT-2A, MT-1X, MT-1F and MT-1E) in three human tumor cell lines (MCF-7, MDA-MB-231 and HeLa). We found that, in all cell types, melatonin increases Cd-induced expression of MT-2A, which is considered to protect against Cd toxicity. As regards MT-1 subtypes, which have been related with cell invasiveness and high histological grade tumors, melatonin caused Cd-induced expression in both breast cancer cell lines to decrease. These effects point towards melatonin's possible role as a preventive agent for carcinogenesis dependent on Cd contamination.     

PJ34, a poly adenosine diphosphate-ribose polymerase inhibitor, attenuates chromate-induced nephrotoxicity

Potassium dichromate (K(2)Cr(2)O(7))-induced nephrotoxicity is associated with oxidative stress. In addition, the activation of the polyadenosine diphosphate-ribose [poly(ADP-ribose)] polymerase-1 (PARP-1) plays a role in the pathophysiology of some diseases associated with oxidative stress. To clarify the potential role of PARP-1 in this experimental model, N-(6-oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethyacetamide HCl (PJ34), a highly specific inhibitor of this enzyme, was used. Nephrotoxicity was induced in rats by a single sc injection of K(2)Cr(2)O(7); studies were performed 2 days later. PJ34 was given intraperitoneally (15 mg/kg) 1 hr before and 1, 5, 24, 26, 31 and 46 hr after K(2)Cr(2)O(7) injection. Nephrotoxicity was evaluated by histological analysis and by measuring blood urea nitrogen, serum creatinine, serum glutathione peroxidase activity and urinary excretion of N-acetyl-beta-D-glucosaminidase. PARP-1 activation was evaluated by the immunostaining of poly(ADP-ribose). In addition, the following markers of oxidative stress were evaluated: 3-nitrotyrosine, 4-hydroxy-2-nonenal, malondialdehyde and protein carbonyl content. K(2)Cr(2)O(7) increased poly(ADP-ribose) content suggesting the PARP-1 activation in this model. PJ34 significantly ameliorated the K(2)Cr(2)O(7)-induced: (i) nephrotoxicity, (ii) poly(ADP-ribose) accumulation and (iii) oxidative stress. It is concluded that PARP-1 is activated and involved, at least in part, in K(2)Cr(2)O(7)-induced nephrotoxicity in rats.