Demographic Factors, Duration and Costs of Hospitalization, and Causes of Death in Patients Intoxicated with Opioids and Amphetamines

Background: Intoxications are medical emergencies and among the significant causes of morbidity and mortality worldwide. In recent years, prevalence of intoxication with opioids and stimulants, such as amphetamines, is increasing particularly among young people. In this study, we investigated demographic factors, duration of hospitalization, costs of hospitalization, and cause of death in patients intoxicated with amphetamines and opioids.Materials and Methods: This study was a prospective descriptive–analytic study. Sampling method was census, and Subjects were patients intoxicated with amphetamines and opioids, alone or combined, who referred to toxicology ward of Ali-Asghar hospital in Isfahan, from October 2009 to April 2010.Results: During 6 months, among 2325 subjects, 419 patients used opioids, 98 patients used amphetamines, and 25 patients used both of them. The mean age of patients in the three groups was not significantly different. Most patients were male in all groups. The most common route of intoxication was orally in opioid group and inhalation in amphetamine group. The most common cause of intoxication was intentional attempt. Vital signs at admission were normal in three groups, but the average of heart rate, body temperature, respiratory rate and blood pressure, was slightly higher in the amphetamine group than the opioid group. Duration and cost of hospitalization were not significantly different between groups. Four patients were died totally and the outcome was not significantly different between groups. The mean age and duration of hospitalization were significantly higher in died compared to living patients.Conclusion: Opioids and amphetamines accounted for high percentages of intoxication, especially in young single men with self-employed job. Therefore, control and prevention of opioids and amphetamines consumption are important ways to reduce this kind of intoxication in this group

CYLD negatively regulates cell-cycle progression by inactivating HDAC6 and increasing the levels of acetylated tubulin

CYLD is a tumour-suppressor gene that is mutated in a benign skin tumour syndrome called cylindromatosis. The CYLD gene product is a deubiquitinating enzyme that was shown to regulate cell proliferation, cell survival and inflammatory responses, mainly through inhibiting NF-κB signalling. Here we show that CYLD controls cell growth and division at the G1/S-phase as well as cytokinesis by associating with α-tubulin and microtubules through its CAP-Gly domains. Translocation of activated CYLD to the perinuclear region of the cell is achieved by an inhibitory interaction of CYLD with histone deacetylase-6 (HDAC6) leading to an increase in the levels of acetylated α-tubulin around the nucleus. This facilitates the interaction of CYLD with Bcl-3, leading to a significant delay in the G1-to-S-phase transition. Finally, CYLD also interacts with HDAC6 in the midbody where it regulates the rate of cytokinesis in a deubiquitinase-independent manner. Altogether these results identify a mechanism by which CYLD regulates cell proliferation at distinct cell-cycle phases

Negative feedback regulation of the ERK1/2 MAPK pathway

The extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) signalling pathway regulates many cellular functions, including proliferation, differentiation, and transformation. To reliably convert external stimuli into specific cellular responses and to adapt to environmental circumstances, the pathway must be integrated into the overall signalling activity of the cell. Multiple mechanisms have evolved to perform this role. In this review, we will focus on negative feedback mechanisms and examine how they shape ERK1/2 MAPK signalling. We will first discuss the extensive number of negative feedback loops targeting the different components of the ERK1/2 MAPK cascade, specifically the direct posttranslational modification of pathway components by downstream protein kinases and the induction of de novo gene synthesis of specific pathway inhibitors. We will then evaluate how negative feedback modulates the spatiotemporal signalling dynamics of the ERK1/2 pathway regarding signalling amplitude and duration as well as subcellular localisation. Aberrant ERK1/2 activation results in deregulated proliferation and malignant transformation in model systems and is commonly observed in human tumours. Inhibition of the ERK1/2 pathway thus represents an attractive target for the treatment of malignant tumours with increased ERK1/2 activity. We will, therefore, discuss the effect of ERK1/2 MAPK feedback regulation on cancer treatment and how it contributes to reduced clinical efficacy of therapeutic agents and the development of drug resistance