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Stifanese R.,National Research Council Italy | Stifanese R.,University of Genoa | Averna M.,University of Genoa | De Tullio R.,University of Genoa | And 10 more authors.
Archives of Biochemistry and Biophysics | Year: 2014

Elevation in [Ca2+]i and activation of calpain-1 occur in central nervous system of SOD1G93A transgenic mice model of amyotrophic lateral sclerosis (ALS), but few data are available about the early stage of ALS. We here investigated the level of activation of the Ca2+-dependent protease calpain-1 in spinal cord of SOD1G93A mice to ascertain a possible role of the protease in the aetiology of ALS. Comparing the events occurring in the 120 day old mice, we found that [Ca2+]i and activation of calpain-1 were also increased in the spinal cord of 30 day old mice, as indicated by the digestion of some substrates of the protease such as nNOS, αII-spectrin, and the NR2B subunit of NMDA-R. However, the digestion pattern of these proteins suggests that calpain-1 may play different roles depending on the phase of ALS. In fact, in spinal cord of 30 day old mice, activation of calpain-1 produces high amounts of nNOS active species, while in 120 day old mice enhanced-prolonged activation of calpain-1 inactivates nNOS and down-regulates NR2B. Our data reveal a critical role of calpain-1 in the early phase and during progression of ALS, suggesting new therapeutic approaches to counteract its onset and fatal course. © 2014 Elsevier Inc. All rights reserved.


Terzioglu B.,Pharmacology and Toxicology Unit | Berkman Z.,Haydarpasa Numune Research and Training Hospital
Journal of Research in Medical Sciences | Year: 2015

Background: Hyperglycemia is frequently encountered in critically ill patients and has been shown to contribute to both morbidity and mortality. We aimed to study the predictive role of blood glucose level in clinical outcomes of mechanically ventilated patients with traumatic brain injury during intensive care unit (ICU) stay and to explore its relationship with Glasgow coma scale (GCS) and acute physiology and chronic health examination (APACHE) II scores that are used in the evaluation of ICU patients as predictor. Materials and Methods: A total of 185 patients with craniocerebral trauma who were hospitalized in the ICU were included in the study. Comparisons of mean glucose values (MGVs) and APACHE II scores between survivors and nonsurvivors were made with Student’s t-test and chi-square test. Survival analysis was performed with log rank (Mantel-Cox) test and Cox regression was used for mortality risk factors analysis. Results: MGVs at the initial, last, and all measurements were significantly higher for nonsurvivors than for survivors. Hazard rate at any given time point for patients with mean glucose value (MGV) between 150 and 179 was found to be 3.691 times that of patients with MGV values between 110 and 149. The hazard rate at any given time point for patients with MGV values ≥180 was found to be 6.571 times that of patients with MGV values between 110 and 149. Conclusion: High glucose level is an independent risk factor for mortality in mechanically ventilated ICU patients with traumatic brain injury. © 2015 Journal of Research in Medical Sciences.


PubMed | Pharmacology and Toxicology Unit
Type: Journal Article | Journal: The Southeast Asian journal of tropical medicine and public health | Year: 2012

Human exposure to cadmium (Cd) produces a wide variety of toxic effects involving many organs and systems, but the kidney is the main organ affected among long-term Cd-exposed people. In the general population, the primary sources of Cd exposure are cigarette smoke and food (shellfish, offal and certain vegetables). The aims of the study were to investigate the association between urinary and blood Cd levels and personal habits relating to Cd intake (consumption of food stuff, water and tobacco smoking), levels of renal biomarkers in the urine or serum of 314 Thai subjects (85 males, 229 females) who resided in Cd-contaminated areas of Mae Sot District, Tak Province, Thailand. Based on the cut-off levels of 1 microg/g creatinine and 5 microg/l for urinary and blood Cd levels, respectively, nearly all subjects had urinary Cd levels lower than cut-off values for urine and blood (88.2 and 77.7%, respectively). Binary logistic backward stepwise regression analysis with five covariates (gender, residential areas, consumption of bamboo or chicken, and smoking status), and eight covariates (residential areas, consumption of beans, pork, fish or liver, types and sources of rice consumed and smoking status) best predicted urinary and blood Cd levels, respectively. For renal biomarkers, N-acetyl-beta-glucosaminidase (NAG) best predicted both urinary and blood Cd with good accuracy. A larger sample size with equal distribution of subjects with low (< 2 microg/g creatinine) and high (> 2 microg/g creatinine) urinary Cd levels should be studied to obtain the regression equation that would best predict Cd body burden.

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