CARDIOVASCULAR RISK FACTORS AS POTENTIAL MARKERS FOR MILD COGNITIVE IMPAIRMENT AND ALZHEIMER’S DISEASE

Background: Mild cognitive impairment (MCI) is an early stage of cognitive decline that has a significant risk of converting to dementia. Cardiovascular pathology appears to have a major impact in cognitive decline, and it is clear that early identification and correction of cardiovascular morbidity could have a major impact on cognitive functioning. Subjects and methods: Our study was conducted in order to identify some cardiovascular risk factors among patients with cognitive decline (MCI or Alzheimer disease-AD) and to find if there is any correlation with the degree of cognitive decline. We evaluated the body mass index, total cholesterol, hypertension, history of smoking, alcohol consumption and diabetes mellitus in patients with MCI and AD, compared with an age-matched control group. Results: Regarding the body mass index, we observed a progressive decrease in patients with MCI and AD, in comparison with the control group. Similar aspects were also observed in the case of cholesterol levels, only that post hoc analysis revealed no significantly statistical differences between MCI and AD groups. The systolic blood pressure was increased in the patients with MCI and AD. Also, as in the case of cholesterol levels, post hoc analysis revealed no significantly statistical differences between MCI and AD groups. Pearson’s correlation showed significant connections between the cardiovascular risk factors and the results of the cognitive evaluation. Conclusions: Our results constitute additional evidence that cardiovascular risk factors are involved in cognitive regression. This finding could have an important impact on the management of dementia

Respiratory and vascular effects of some fractions isolated from red wine

We have isolated a series of fractions (T1–T6) from a sample of red wine and studied their influence on cellular respiration and behaviour of blood vessels, by in vitro analysis of striated muscle and liver of frog (Rana ridibunda, Pall), and of fragments of Wistar rat aorta artery. Different biological effects were registered, according to the type of tissues, composition of fractions (polyphenol proportion), and duration of registrations. The dominant effect on cellular respiration consisted in its stimulation, registered at fractions richer in polyphenols – T2 and T3, more pronounced than that produced by wine and more prominent at liver than at muscles. The same fractions clearly influenced the smooth muscles of aorta artery, determining an important vasodilatation effect. The other fractions had a weaker or inhibiting action on cellular respiration and did not show evident vascular effects. The results pointed out a series of useful pharmacological properties of certain studied wine fractions

Alzheimer’s Disease Pharmacotherapy in Relation to Cholinergic System Involvement

Alzheimer’s disease, a major and increasing global health challenge, is an irreversible, progressive form of dementia, associated with an ongoing decline of brain functioning. The etiology of this disease is not completely understood, and no safe and effective anti-Alzheimer’s disease drug to prevent, stop, or reverse its evolution is currently available. Current pharmacotherapy concentrated on drugs that aimed to improve the cerebral acetylcholine levels by facilitating cholinergic neurotransmission through inhibiting cholinesterase. These compounds, recognized as cholinesterase inhibitors, offer a viable target across key sign domains of Alzheimer’s disease, but have a modest influence on improving the progression of this condition. In this paper, we sought to highlight the current understanding of the cholinergic system involvement in Alzheimer’s disease progression in relation to the recent status of the available cholinesterase inhibitors as effective therapeutics

Exploring the Therapeutic Potential of Cannabinoid Receptor Antagonists in Inflammation, Diabetes Mellitus, and Obesity

Recently, research has greatly expanded the knowledge of the endocannabinoid system (ECS) and its involvement in several therapeutic applications. Cannabinoid receptors (CBRs) are present in nearly every mammalian tissue, performing a vital role in different physiological processes (neuronal development, immune modulation, energy homeostasis). The ECS has an essential role in metabolic control and lipid signaling, making it a potential target for managing conditions such as obesity and diabetes. Its malfunction is closely linked to these pathological conditions. Additionally, the immunomodulatory function of the ECS presents a promising avenue for developing new treatments for various types of acute and chronic inflammatory conditions. Preclinical investigations using peripherally restricted CBR antagonists that do not cross the BBB have shown promise for the treatment of obesity and metabolic diseases, highlighting the importance of continuing efforts to discover novel molecules with superior safety profiles. The purpose of this review is to examine the roles of CB1R and CB2Rs, as well as their antagonists, in relation to the above-mentioned disorders

Identification of Y-Box Binding Protein 1 As a Core Regulator of MEK/ERK Pathway-Dependent Gene Signatures in Colorectal Cancer Cells

Transcriptional signatures are an indispensible source of correlative information on disease-related molecular alterations on a genome-wide level. Numerous candidate genes involved in disease and in factors of predictive, as well as of prognostic, value have been deduced from such molecular portraits, e.g. in cancer. However, mechanistic insights into the regulatory principles governing global transcriptional changes are lagging behind extensive compilations of deregulated genes. To identify regulators of transcriptome alterations, we used an integrated approach combining transcriptional profiling of colorectal cancer cell lines treated with inhibitors targeting the receptor tyrosine kinase (RTK)/RAS/mitogen-activated protein kinase pathway, computational prediction of regulatory elements in promoters of co-regulated genes, chromatin-based and functional cellular assays. We identified commonly co-regulated, proliferation-associated target genes that respond to the MAPK pathway. We recognized E2F and NFY transcription factor binding sites as prevalent motifs in those pathway-responsive genes and confirmed the predicted regulatory role of Y-box binding protein 1 (YBX1) by reporter gene, gel shift, and chromatin immunoprecipitation assays. We also validated the MAPK-dependent gene signature in colorectal cancers and provided evidence for the association of YBX1 with poor prognosis in colorectal cancer patients. This suggests that MEK/ERK-dependent, YBX1-regulated target genes are involved in executing malignant properties

Validity and reliability of the Romanian version of the Hill-Bone compliance to high blood pressure therapy scale

Romania is considered a country with high cardiovascular risk, arterial hypertension and its complications accounting for about 60% of total deaths. The management of high blood pressure often involves a combination of both therapeutic regimens as well as lifestyle changes, to which patients have to be adherent. In order to assess patients adherence to professionals’ recommendations, validated tools are needed. The aim of our study was to translate, culturally adapt and validate the Hill-Bone Compliance to High Blood Pressure Therapy Scale into Romanian. The study included 215 participants from Iasi, North-Eastern Romania. The internal consistency of the instrument was measured with Cronbach’s alpha coefficient, while the construct validity was determined using exploratory factor analysis and principal component extraction with promax rotation. Sampling adequacy and appropriateness of data for factor analysis was measured using Kaiser-Meyer-Olkin (KMO) statistics and Bartlett’s test of sphericity. Our statistical analysis revealed a Cronbach’s alpha coefficient of 0.733 (73.3%) and a Kaiser-Meyer-Olkin (KMO) Measure of Sampling Adequacy of 0.697. The chi square test demonstrated that the overall perfect adherence was not significantly associated with the number of medications taken per day variable (p = 0.721). The Romanian version of the Hill-Bone Compliance to High Blood Pressure Therapy Scale demonstrated suitability for its use in evaluating adherence in the intended population