Acetaldehyde elicits ERK phosphorylation in the rat nucleus accumbens and extended amygdala

Recent advances suggest that acetaldehyde mediates some of the neurobiological properties of ethanol. In a recent study, we have shown that ethanol elicits the phosphorylation of extracellular signal‐regulated kinase (pERK) in the nucleus accumbens and extended amygdala, via a dopamine D₁ receptor‐mediated mechanism. The aim of this study was to determine whether acetaldehyde and ethanol‐derived acetaldehyde elicit the activation of ERK in the nucleus accumbens and extended amygdala. The effects of acetaldehyde (10 and 20 mg/kg) and ethanol (1 g/kg), administered to rats intragastrically, were assessed by pERK peroxidase immunohistochemistry. To establish the role of ethanol‐derived acetaldehyde, the alcohol dehydrogenase inhibitor, 4‐methylpyrazole (90 mg/kg), and the acetaldehyde‐sequestering agent, D ‐penicillamine (50 mg/kg), were administered before ethanol. Acetaldehyde increased pERK immunoreactivity in the nucleus accumbens and extended amygdala. Inhibition of ethanol metabolism and sequestration of newly synthesized acetaldehyde completely prevented ERK activation by ethanol. In addition, to establish the role of D₁ receptors stimulation in acetaldehyde‐elicited ERK phosphorylation, we studied the effect of the D₁ receptor antagonist, SCH 39166. Pretreatment with the D₁ receptor antagonist (50 μg/kg) fully prevented acetaldehyde‐elicited ERK activation. Overall, these results indicate that ethanol activates ERK by means of its metabolic conversion into acetaldehyde and strengthen the view that acetaldehyde is a centrally acting compound with a pharmacological profile similar to ethanol. Synapse 64:916–927, 2010. © 2010 Wiley‐Liss, Inc.     

Adenocarcinoma vesical primario en extrofia vesical no corregida

We report a 60 years old patient with a not repaired exstrophic bladder, who develops an adenocarcinoma on his bladder and review of the literature.     

Developing and piloting a communication assessment tool assessing patient perspectives on communication with pharmacists (CAT-Pharm)

International Journal of Clinical Pharmacy - Effective communication strategies in health care help to enhance patient empowerment and improve clinical outcomes. Adapt the original Communication...     

Using collaborative learning to improve diabetes care and outcomes: The VIDA project

The prevalence of diabetes in Mexico among those 20–64 years of age has increased from 7.2% in 1993 to 10.7% in 2000. National population-based surveys in Mexico demonstrated that 50% of the total population with diabetes had blood glucose levels of 200 mg/dl or higher. Thus, diabetes care has become one of the most important public health challenges in this country. The aim of the study was to improve the quality of diabetes care in primary health care centers using the chronic care model and the breakthrough series (BTS) collaborative methodology.MethodsTen public health centers in the cities of Xalapa and Veracruz were randomly selected to participate in the project. Five of the health centers were randomly assigned to receive the intervention (intervention group) and the other five followed usual care (usual care group). The intervention was evaluated by A1c test before and after the intervention in both groups of patients. Patients were followed for 18 months from November 2002 to May 2004. Results were adjusted for the clustering of patients within practices and baseline measure.ResultsThe proportion of people with good glycemic control (A1c < 7%) among those in the intervention group increased from 28% before the intervention to 39% after the intervention. The proportion of patients achieving three or more quality improvement goals increased from 16.6% to 69.7% (p < 0.001) among the intervention group while the usual care group experienced a non-significant decrease from 12.4% to 5.9% (p = 0.118). The focus on the primary care team and the participation of people with diabetes were strategic elements incorporated into the methodology, expected to ensure sustainability of continued improvement of health outcomes.ConclusionsThe intervention introduced modifications to solve problems identified by health teams in their practice and improved process and outcome measures of quality diabetes care. Most of the actions were directed at four components of the chronic care model: self-management support, decision support, delivery system design, and clinical information systems.     

Triple negative breast cancer: looking for the missing link between biology and treatments

The so called “Triple Negative Breast Cancer” (TNBC) represents approximately 15-20% of breast cancers. This acronym simply means that the tumour does not express oestrogen receptor (ER) and progesterone receptor (PR) and does not exhibit amplification of the human epidermal growth factor receptor 2 (HER2) gene. Despite this unambiguous definition, TNBCs are an heterogeneous group of tumours with just one common clinical feature: a distinctly aggressive nature with higher rates of relapse and shorter overall survival in the metastatic setting compared with other subtypes of breast cancer. Because of the absence of well-defined molecular targets, cytotoxic chemotherapy is currently the only treatment option for TNBC.In the last decades, the use of more aggressive chemotherapy has produced a clear improvement of the prognosis in women with TNBC, but this approach results in an unacceptable deterioration in the quality of life, also if some support therapies try to relieve patients from distress. In addition, there is the general belief that it is impossible to further improve the prognosis of TNBC patients with chemotherapy alone. In view of that, there is a feverish search for new “clever drugs” able both to rescue chemo-resistant, and to reduce the burden of chemotherapy in chemo-responsive TNBC patients.A major obstacle to identifying actionable targets in TNBC is the vast disease heterogeneity both inter-tumour and intra-tumour and years of study have failed to demonstrate a single unifying alteration that is targetable in TNBC. TNBC is considered the subtype that best benefits from the neoadjuvant model, since the strong correlation between pathological Complete Response and long-term Disease-Free-Survival in these patients.In this review, we discuss the recent discoveries that have furthered our understanding of TNBC, with a focus on the subtyping of TNBC. We also explore the implications of these discoveries for future treatments and highlight the need for a completely different type of clinical trials.     

N, N' (4,5-dihydro-1h-imidazol-2-yl)3-aza-1,10-decane-diamine and N, N'(4,5-dihydro-1H-imidazol-2-yl)3-aza-1, 10-dodecane-diamine antagonize cell proliferation as selective ligands towards topoisomerase II

New alkyl imidazoline derivatives have been synthesized as potential anti-cancer agents. The anti-proliferative activity of these compounds, evaluated against representative human haematological and solid neoplastic cell lines, showed that N, N'-di (4,5-dihydro-1H-imidazol-2-yl)3-aza-1,10-decane-diamine (8) and N, N'-di (4,5-dihydro-1H-imidazol-2-yl)3-aza-1,10-dodecane-diamine (9) were the most active compounds; in fact, they inhibited the cell proliferation at submicromolar concentrations. In enzyme assays, compound 9 turned out to be an inhibitor of topoisomerase II at concentrations comparable with those of the reference topoisomerase II inhibitor, etoposide.     

Synthetic peptides outside the spike protein heptad repeat regions as potent inhibitors of SARS-associated coronavirus

A novel severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) has been identified as the aetiological agent of SARS. We previously isolated and characterized SARS-CoV and SARS-CoV-like viruses from human and animals, respectively, suggesting that SARS could be transmitted from wild/farmed animals to humans. Comparison of the viral genomes indicated that sequence variation between animal and human isolates existed mainly in the spike (S) gene. We hypothesized that these variations may underlie a change of binding specificity of the S protein to the host cells, permitting viral transmission from animals to humans. Here we report that four 20-mer synthetic peptides (S protein fragments), designed to span these sequence variation hotspots, exhibited significant antiviral activities in a cell line. SARS-CoV infectivity was reduced over 10 000-fold through pre-incubation with two of these peptides, while it was completely inhibited in the presence of three peptides. Molecular modelling of the SARS-CoV peplomer suggests that three of these antiviral peptides map to the interfaces between the three monomers of the trimeric peplomer rather than the heptad repeat region from which short peptides are known to inhibit viral entry. Our results revealed novel regions in the spike protein that can be targeted to inhibit viral infection. The peptides identified in this study could be further developed into antiviral drugs.