The Role of Visinin-Like Protein-1 in the Pathophysiology of Alzheimer's Disease.

Calcium ions are crucial in the process of information transmission and integration in the central nervous system (CNS). These ions participate not only in intracellular mechanisms but also in intercellular processes. The changes in the concentration of Ca2 + ions modulate synaptic transmission, whereas neuronal activity induces calcium ion waves. Disturbed calcium homeostasis is thought to be one of the main features in the pathophysiology of Alzheimer's disease (AD), and AD pathogenesis is closely connected to Ca2 + signaling pathways. The effects of changes in neuronal Ca2 + are mediated by neuronal calcium sensor (NCS) proteins. It has been revealed that NCS proteins, with special attention to visinin-like protein 1 (VILIP-1), might have a connection to the etiology of AD. In the CNS, VILIP-1 influences the intracellular neuronal signaling pathways involved in synaptic plasticity, such as cyclic nucleotide cascades and nicotinergic signaling. This particular protein is implicated in calcium-mediated neuronal injury as well. VILIP-1 also participates in the pathological mechanisms of altered Ca2 + homeostasis, leading to neuronal loss. These findings confirm the utility of VILIP-1 as a useful biomarker of neuronal injury. Moreover, VILIP-1 plays a vital role in linking calcium-mediated neurotoxicity and AD-type pathological changes. The disruption of Ca2 + homeostasis caused by AD-type neurodegeneration may result in the damage of VILIP-1-containing neurons in the brain, leading to increased cerebrospinal fluid levels of VILIP-1. Thus, the aim of this overview is to describe the relationships of the NCS protein VILIP-1 with the pathogenetic factors of AD and neurodegenerative processes, as well as its potential clinical usefulness as a biomarker of AD. Moreover, we describe the current and probable therapeutic strategies for AD, targeting calcium-signaling pathways and VILIP-1.

The salivary ß-HEX A% index as an excellent marker of periodontitis in smoking alcohol-dependent persons.

BACKGROUND: Severe periodontitis leading to tooth loss is found in 5-15% of most populations worldwide. AIM: The applicability of salivary ß -hexosaminidase (ß-HEX A%, percentage of ß-HEX A isoenzyme to total ß-HEX) and ß-HEX B% (ß-HEX B/ß-HEX) indexes was investigated as a possible marker of periodontitis. METHODS: Thirty three alcohol-dependent smokers (AS) and 32 healthy controls (C) were enrolled in the study. The activity of ß-HEX was measured spectrophotometrically. RESULTS: ß-HEX A% was significantly higher and ß-HEX B% was lower in AS than in C group. We found a significant correlation between ß-HEX A% and gingival index (GI) and an inverse correlation between ß-HEX A% and salivary flow (SF), in all groups. Salivary ß-HEX A% index in smoking alcoholics at 0.23 had excellent sensitivity (96%) and specificity (91%); the AUC for ß-HEX A% was high (0.937). There were no correlations between amount/duration-time of alcohol drinking/smoking and ß-HEX A% or ß-HEX B%. We found significant correlations between the time period of denture wearing and GI, papilla bleeding index (PBI), and decayed missing filled teeth index (DMFT) and between GI and the amount of smoked cigarettes per day. CONCLUSION: Bad periodontal state was most likely due to the nicotine dependence. Salivary ß-HEX A% is a promising excellent marker for the diagnosis of periodontitis.

The activity of serum beta-galactosidase in colon cancer patients with a history of alcohol and nicotine dependence: preliminary data.

INTRODUCTION: Beta-galactosidase (GAL) is a lysosomal exoglycosidase involved in the catabolism of glycoconjugates through the sequential release of beta-linked terminal galactosyl residues. The stimulation of activity of exoglycosidases and other degradative enzymes has been noted in cancers as well as in alcohol and nicotine addiction separately. This is the first study to evaluate the activity of the serum senescence marker GAL in colon cancer patients with a history of alcohol and nicotine dependence, as a potential factor of worse cancer prognosis. MATERIAL AND METHODS: The material was serum of 18 colon cancer patients and 10 healthy volunteers. Ten colon cancer patients met alcohol and nicotine dependence criteria. The activity of beta-galactosidase (pkat/ml) was determined by the colorimetric method. Comparisons between groups were made using the Kruskal-Wallis analysis and differences evaluated using the Mann-Whitney U test. Spearman's rank correlation coefficient was used to measure the statistical dependence between two variables. RESULTS: The activity of serum GAL was significantly higher in colon cancer patients with a history of alcohol and nicotine dependence, in comparison to colon cancer patients without a history of drinking/smoking (p=0.015; 46% increase), and the controls (p=0.0002; 81% increase). The activity of serum GAL in colon cancer patients without a history of alcohol/nicotine dependence was higher than the activity in the controls (p = 0.043; 24% increase). DISCUSSION/CONCLUSION: Higher activity of beta-galactosidase may potentially reflect the accelerated growth of the cancer, invasion, metastases, and maturation, when alcohol and nicotine dependence coincide with colon cancer. For a better prognosis of colon cancer, alcohol and nicotine withdrawal seems to be required.