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.

Correlations between Cognitive Evaluation and Metabolic Syndrome.

One of the most common medical diseases is metabolic syndrome (MetS), which encompasses diabetes and obesity. It has a systemic effect, which has long-lasting consequences on the body that are still not fully understood. The objectives of the study were to investigate the association between the severity of metabolic imbalances, insulin resistance, leptin concentration, and the presence of cognitive disorders and to assess the possible protective role of some classes of drugs used in the treatment of type 2 diabetes mellitus (T2D) and dyslipidemia in order to identify a viable target in the near future. The study included 148 diabetic patients. Standardized tests for the evaluation of cognition, including Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), were applied to all study participants. Serum concentrations of leptin and insulin were determined using the enzyme-linked immunosorbent assay method (ELISA), and insulin resistance was calculated using the homeostatic model assessment for insulin resistance (HOMA-IR). We found that MMSE and MoCA scores were associated with anthropometric parameters, and MoCA was associated with glycemic control parameters and leptin levels. Further research is needed in order to establish the magnitude of the relationship between metabolic syndrome components and cognitive decline in diabetic patients.

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.

Therapeutic Implications of Renin-Angiotensin System Modulators in Alzheimer's Dementia.

The Renin-Angiotensin System (RAS) has attracted considerable interest beyond its traditional cardiovascular role due to emerging data indicating its potential involvement in neurodegenerative diseases, including Alzheimer's dementia (AD). This review investigates the therapeutic implications of RAS modulators, specifically focusing on angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and renin inhibitors in AD. ACEIs, commonly used for hypertension, show promise in AD by reducing angiotensin (Ang) II levels. This reduction is significant as Ang II contributes to neuroinflammation, oxidative stress, and ß-amyloid (Aß) accumulation, all implicated in AD pathogenesis. ARBs, known for vasodilation, exhibit neuroprotection by blocking Ang II receptors, improving cerebral blood flow and cognitive decline in AD models. Renin inhibitors offer a novel approach by targeting the initial RAS step, displaying anti-inflammatory and antioxidant effects that mitigate AD degeneration. Preclinical studies demonstrate RAS regulation's favorable impact on neuroinflammation, neuronal damage, cognitive function, and Aß metabolism. Clinical trials on RAS modulators in AD are limited, but with promising results, ARBs being more effective that ACEIs in reducing cognitive decline. The varied roles of ACEIs, ARBs, and renin inhibitors in RAS modulation present a promising avenue for AD therapeutic intervention, requiring further research to potentially transform AD treatment strategies.

The Impact of Some Modulators of the Renin-Angiotensin System on the Scopolamine-Induced Memory Loss Mice Model.

As some of the renin-angiotensin-aldosterone system (RAAS)-dependent mechanisms underlying the cognitive performance modulation could include oxidative balance alterations, in this study we aimed to describe some of the potential interactions between RAAS modulators (Losartan and Ramipril) and oxidative stress in a typical model of memory impairment. In this study, 48 white male Swiss mice were divided into six groups and received RAAS modulators (oral administration Ramipril 4 mg/kg, Losartan 20 mg/kg) and a muscarinic receptors inhibitor (intraperitoneal injection scopolamine, 0.5 mg/kg) for 8 consecutive days. Then, 24 h after the last administration, the animals were euthanized and whole blood and brain tissues were collected. Biological samples were then processed, and biochemical analysis was carried out to assess superoxide dismutase and glutathione activities and malondialdehyde concentrations. In the present experimental conditions, we showed that RAAS modulation via the angiotensin-converting enzyme inhibition (Ramipril) and via the angiotensin II receptor blockage (Losartan) chronic treatments could lead to oxidative stress modulation in a non-selective muscarinic receptors blocker (scopolamine) animal model. Our results showed that Losartan could exhibit a significant systemic antioxidant potential partly preventing the negative oxidative effects of scopolamine and a brain antioxidant potential, mainly by inhibiting the oxidative-stress-mediated cellular damage and apoptosis. Ramipril could also minimize the oxidative-mediated damage to the lipid components of brain tissue resulting from scopolamine administration. Both blood serum and brain changes in oxidative stress status were observed following 8-day treatments with Ramipril, Losartan, scopolamine, and combinations. While the serum oxidative stress modulation observed in this study could suggest the potential effect of RAAS modulation and scopolamine administration on the circulatory system, blood vessels endothelia, and arterial tension modulation, the observed brain tissues oxidative stress modulation could lead to important information on the complex interaction between renin-angiotensin and cholinergic systems.

The Skin and Natural Cannabinoids-Topical and Transdermal Applications.

The chemical constituents of the Cannabis plant known as cannabinoids have been extensively researched for their potential therapeutic benefits. The use of cannabinoids applied to the skin as a potential method for both skin-related benefits and systemic administration has attracted increasing interest in recent years. This review aims to present an overview of the most recent scientific research on cannabinoids used topically, including their potential advantages for treating a number of skin conditions like psoriasis, atopic dermatitis, and acne. Additionally, with a focus on the pharmacokinetics and security of this route of administration, we investigate the potential of the transdermal delivery of cannabinoids as a method of systemic administration. The review also discusses the restrictions and difficulties related to the application of cannabinoids on the skin, emphasizing the potential of topical cannabinoids as a promising route for both localized and systemic administration. More studies are required to fully comprehend the efficacy and safety of cannabinoids in various settings.

Self-Medication in Rural Northeastern Romania: Patients' Attitudes and Habits.

In recent years, many healthcare systems, along with healthcare professionals, have provided services in a patient-centered manner, in which patients are key actors in the care process. Encouraging self-care creates responsible patients, but it must be practiced responsibly. This study aims to analyze the tendency towards self-medication for patients from a rural area in Northeastern Romania. Data were collected using a questionnaire, which consisted of 25 questions, that has been developed by the research team. Student's T test or one-way ANOVA was used, and the reliability of the questionnaire was calculated using Cronbach's alpha coefficient. Fifty-eight patients agreed to participate and were interviewed. The results of the study suggest that respondents practice self-medication, which they resort to when their condition cannot be treated with natural remedies or herbs and when it impairs their ability to do their daily activities. Self-medication could be explained by the lack of self-care services as well as the trust patients have in the specific treatment. Patients prefer asking the pharmacist for drugs instead of visiting a physician, which could be due to higher accessibility and time-efficiency, while also being prone to stock up on certain medications due to limited access to healthcare.

Impact of the Renin-Angiotensin System on the Pathogeny and Pharmacotherapeutics of Neurodegenerative Diseases.

Brain neurodegenerative diseases (BND) are debilitating conditions that are especially characteristic of a certain period of life and considered major threats to human health. Current treatments are limited, meaning that there is a challenge in developing new options that can efficiently tackle the different components and pathophysiological processes of these conditions. The renin-angiotensin-aldosterone system (RAS) is an endocrine axis with important peripheral physiological functions such as blood pressure and cardiovascular homeostasis, as well as water and sodium balance and systemic vascular resistance-functions which are well-documented. However, recent work has highlighted the paracrine and autocrine functions of RAS in different tissues, including the central nervous system (CNS). It is known that RAS hyperactivation has pro-inflammatory and pro-oxidant effects, thus suggesting that its pharmacological modulation could be used in the management of these conditions. The present paper underlines the involvement of RAS and its components in the pathophysiology of BNDs such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), Huntington's disease (HD), motor neuron disease (MND), and prion disease (PRD), as well as the identification of drugs and pharmacologically active substances that act upon RAS, which could alleviate their symptomatology or evolution, and thus, contribute to novel therapeutic approaches.

Endocannabinoid Modulation in Neurodegenerative Diseases: In Pursuit of Certainty.

Neurodegenerative diseases are an increasing cause of global morbidity and mortality. They occur in the central nervous system (CNS) and lead to functional and mental impairment due to loss of neurons. Recent evidence highlights the link between neurodegenerative and inflammatory diseases of the CNS. These are typically associated with several neurological disorders. These diseases have fundamental differences regarding their underlying physiology and clinical manifestations, although there are aspects that overlap. The endocannabinoid system (ECS) is comprised of receptors (type-1 (CB1R) and type-2 (CB2R) cannabinoid-receptors, as well as transient receptor potential vanilloid 1 (TRPV1)), endogenous ligands and enzymes that synthesize and degrade endocannabinoids (ECBs). Recent studies revealed the involvement of the ECS in different pathological aspects of these neurodegenerative disorders. The present review will explore the roles of cannabinoid receptors (CBRs) and pharmacological agents that modulate CBRs or ECS activity with reference to Alzheimer's Disease (AD), Parkinson's Disease (PD), Huntington's Disease (HD) and multiple sclerosis (MS).

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.

Renal Contributions in the Pathophysiology and Neuropathological Substrates Shared by Chronic Kidney Disease and Alzheimer's Disease.

Chronic kidney disease and Alzheimer's disease are chronic conditions highly prevalent in elderly communities and societies, and a diagnosis of them is devastating and life changing. Demanding therapies and changes, such as non-compliance, cognitive impairment, and non-cognitive anomalies, may lead to supplementary symptoms and subsequent worsening of well-being and quality of life, impacting the socio-economic status of both patient and family. In recent decades, additional hypotheses have attempted to clarify the connection between these two diseases, multifactorial in their nature, but even so, the mechanisms behind this link are still elusive. In this paper, we sought to highlight the current understanding of the mechanisms for cognitive decline in patients with these concurrent pathologies and provide insight into the relationship between markers related to these disease entities and whether the potential biomarkers for renal function may be used for the diagnosis of Alzheimer's disease. Exploring detailed knowledge of etiologies, heterogeneity of risk factors, and neuropathological processes associated with these conditions opens opportunities for the development of new therapies and biomarkers to delay or slow their progression and validation of whether the setting of chronic kidney disease could be a potential determinant for cognitive damage in Alzheimer's disease.

Brain renin-angiotensin system in cognitive function: pre-clinical findings and implications for prevention and treatment of dementia.

Biochemical, physiological and functional studies suggest that the brain renin-angiotensin system (RAS) is regulated independently of the peripheral RAS. Also, all enzymes and peptides necessary for the biosynthesis of various angiotensins have been recognized within the central nervous system. There are divergent opinions concerning the localization of the different components of this system which is not fully understood. It is believed that central actions of angiotensins are not exclusively associated with their traditional roles, many studies showing that central angiotensins are also involved in learning and memory processes. Moreover, clinical trials and studies on animal models suggest that pharmacological manipulation of angiotensin ligands may be of clinical importance in slowing or even stopping the cognitive deterioration seen in vascular dementia and Alzheimer's disease.

A Comparative Study on the Memory-Enhancing Actions of Oral Renin-Angiotensin System Altering Drugs in Scopolamine-Treated Mice.

This study was designed to evaluate the spatial working memory (as studied in Y-maze) or short-term and long-term spatial memory (assessed in radial 8 arms-maze task), in a scopolamine-induced memory deficits model in mice, by the oral administration of 2 angiotensin-converting enzyme inhibitors-captopril and ramipril and also the effects of the AT1 receptor antagonist, losartan. The present article was initiated as a reaction to the clinical setting of hypertensive disease, which involves lifelong administration of antihypertensive drugs, dietary or lifestyle constraints, and aging, which all take a toll on the higher functions of the nervous system. Most of the patients with cognitive decline suffer of various metabolic imbalances, hypertension, cardiac and kidney disease, many of them which are treated with oral administration of Renin-angiotensin aldosterone system-altering agents like those presented above. Our results showed a protective effect of captopril, ramipril, and losartan prescopolamine administration on spontaneous alternation in Y-maze task, as compared to scopolamine-alone treated mice, as well as decreased number of working memory errors and reference memory errors in radial-arm maze for both losartan + scopolamine and ramipril + scopolamine groups versus scopolamine alone. This could have a therapeutical relevance, especially since oral administration was preferred in our report, as it is used in the therapeutic procedures in humans, further enhancing the similarities with the clinical conditions.

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.

Intracerebroventricular Coadministration of Protoxin-II and Trace Elements in Rats Enhances the Analgesic Effect of the 1.7 Voltage-Gate Sodium Channel Blocker.

Pain continues to be a global unmet medical need, and the current recommendations for its management require a constant exploration of new drugs that target multiple pain mechanisms, with an improved safety profile and increased treatment adherence. Currently, the enriched distribution and localization within nociceptors of the selective channel blockers and the critical role played by sodium channels in neuronal excitability nominate isoforms as specific targets to generate innovative compounds. In the present report, we verified the hypothesis that coadministration of Protoxin-II, a selective sodium channel inhibitor, and trace elements has direct and improved antinociceptive effects. Groups of seven Wistar rats were treated intracerebroventricularly with a combination of MgCl2, CdCl2, and ZnCl2 and Protoxin-II, respectively, and with Protoxin-II alone (positive) or saline (negative) for controls. Evaluations were performed by nociception assay. Coadministration of these drugs caused an increase in the maximum possible effect of up to 40% as compared with the control groups. Our findings indicate that selective channel blockers continue to be an important nociception target and that the use of trace elements may provide simple but effective means of control over sodium channel blockers' risks, potentially lowering the necessary analgesic doses, thus improving the efficacy and safety profile.

Angiotensin peptides and their pleiotropic actions.

The concept of tissue renin-angiotensin systems (RAS) is now well established and it is now usual to think in terms of renal and tissue systems. At the same time it has emerged that angiotensin II (Ang II) is not the only biologically active peptide generated by the RAS. At least three others have been identified: the heptapeptide Ang III, the hexapeptide Ang IV and Ang 1-7. Specific receptors exits for the last two peptides. In addition, the range of possible physiological and pathophysiological properties for Ang II has been expanding. The current perception of the RAS is therefore that of a much more complex system than previously believed, with autocrine, paracrine and endocrine properties extending beyond the cardiovascular system. This mini-review focuses on the synthetic pathways of the Ang peptides and describes some of their pleiotropic actions.

Biphasic effects of angiotensin (1-7) and its interactions with angiotensin II in rat aorta.

Using isolated rat aortic rings perfused with Krebs-Henseleit saline, the vascular effects of angiotensin (1-7) (Ang [1-7]) and its interactions with angiotensin II (Ang II) were investigated. Ang (1-7) induced endothelium-dependent relaxation and vasodilating effects in preparations precontracted with phenylephrine. Without preconstriction, Ang (1-7) at high doses (10(-6) 10(-5) M) produced either a significant inhibition of Ang II-induced vasoconstriction or a non-tachyphylactic vasopressor response. While losartan inhibited the vasoconstriction induced by Ang (1-7), A779 blocked only its relaxation. Unlike losartan, blockade of AT(2)-receptors with PD 123319 had no effect. Taking into account the biphasic effects of angiotensin (1-7), we propose that it is one of the active components of the renin-angiotensin system, which is involved as a modulator both in the counter-regulatory actions of Ang II and in the self-regulation of its own vasodilating effects.

Comparative study of the inhibitory effects of adrenomedullin on angiotensin II contraction in rat conductance and resistance arteries.

Adrenomedullin (ADM), a ubiquitous vasoactive peptide, has been the target of a multitude of studies concerning its effect on the vascular tone. The present work aims at clarifying a series of its interactions with the renin-angiotensin system. The study uses the rat aorta ring as a model of conductance vessels, with or without vascular endothelium, and the second order branch of rat mesenteric arteries as a model of resistance arteries. Interactions between various concentrations of ADM and angiotensin II (Ang II) were studied, in the presence of L-NAME (a nitric oxide [NO] synthase inhibitor) and methylene blue (MB; a soluble guanylate cyclase inhibitor). Results point out differences in the mechanism of the inhibitory action of ADM upon Ang II effects in the two vessel types studied. Inhibition of Ang II contraction by ADM involves guanylate cyclase in both cases. However, NO is involved in ADM-induced inhibition of angiotensinergic vasoconstriction only in the conductance arteries, not in the resistance ones.

Deuterium-depleted water has stimulating effects on long-term memory in rats.

Deuterium-depleted water (DDW) is a water which has a 6-7-fold less concentration of the naturally occurring deuterium (20-25ppm vs. 150ppm). While administrated for a longer period, it may reduce the concentration of deuterium throughout the body, thus activating cellular mechanisms which are depending on protons (channels, pumps, enzyme proteins). The aim of the present work was to study, for the first time in our knowledge, the possible influence of deuterium-depleted water (DDW) chronic administration in normal Wistar rats, as compared to a control group which received distilled water, on spatial working memory and the locomotor activity (as studied through Y-maze) or both short-term and long-term spatial memory (assed in radial 8 arms-maze task). Our results presented here showed no significant modifications in terms of spatial working memory (assessed through spontaneous alternation percentage) and locomotor activity (expressed through the number of arm entries) in Y-maze, as a result of DDW ingestion. Also, no significant differences between the DDW and control group were found in terms of the number of working memory errors in the eight-arm radial maze, as a parameter of short-term memory. Still, we observed a significant decrease for the number of reference memory errors in the DDW rats. In this way, we could speculate that the administration of DDW may generate an improvement of the reference memory, as an index of long-term memory. Thus, we can reach the conclusion that the change between the deuterium/hydrogen balance may have important consequences for the mechanisms that govern long-term memory, as showed here especially in the behavioral parameters from the eight-arm radial maze task.

Angiotensin-(1-7) central administration induces anxiolytic-like effects in elevated plus maze and decreased oxidative stress in the amygdala.

There is increasing evidence that besides the well-known angiotensin (Ang) II, other renin-angiotensin system (RAS) peptides, including Ang-(1-7), could have important effects at the central level. However, very few things are known about the central actions of Ang-(1-7), while the effects of its administration alone on anxiety have not been tested to date, to the best of our knowledge. In this way, we were interested in studying the effects of Ang-(1-7) intracerebroventricular administration on anxiety levels, as studied through some main behavioral parameters in the elevated plus maze, as well as the importance of Ang-(1-7) in the oxidative stress status from the amygdala, which is one of the key brain regions involved in mediating anxiety. We report here a possible anxiolytic-like effect of Ang-(1-7) administration, as demonstrated by the increased percentage of time spent and frequency of entries in the open arms of the elevated plus maze, as well as increased head-dipping behavior in the open arms and decreased stretching in closed arms. Also some antioxidant effects of Ang-(1-7) are suggested since a significant increase of GPX specific activity and a decrease of the main peroxidation marker MDA were observed in the amygdala. Moreover, we found a significant correlation between most of the behavioral parameters in the elevated plus maze and the levels of the oxidative stress markers. However, further studies are necessary in order to elucidate the effects of Ang-(1-7) administration on anxiety and oxidative stress status and also on the possible correlation that might exists between these aspects.