Comprehensive Analysis of Novel Synergistic Antioxidant Formulations: Insights into Pharmacotechnical, Physical, Chemical, and Antioxidant Properties.

(1) Background: Oxidative stress plays a pivotal role in the pathogenesis of various diseases, including neurodegenerative disorders, cardiovascular diseases, cancer, and diabetes, highlighting the pressing need for effective antioxidant interventions. (2) Methods: In this study, we aimed to develop and characterise two novel antioxidant formulations, F3 and F4, as therapeutic interventions for oxidative stress-related conditions. (3) Results: The physicochemical characterisation, preformulation analysis, formulation, preparation of filling powders for capsules, capsule content evaluation, and antioxidant activity assessment of the two novel antioxidant formulations were assessed. These formulations comprise a combination of well-established antioxidants like quercetin, biotin, coenzyme Q10, and resveratrol. Through comprehensive testing, the formulations' antioxidant efficacy, stability, and potential synergistic interactions were evaluated. (4) Conclusions: The findings underscore the promising potential of these formulations as therapeutic interventions for oxidative stress-related disorders and highlight the significance of antioxidant interventions in mitigating their progression.

MMP1, MMP9, MMP11 and MMP13 in melanoma and its metastasis - key points in understanding the mechanisms and celerity of tumor dissemination.

BACKGROUND: Matrix metalloproteinase (MMP)1, MMP9, MMP11, and MMP13 are overexpressed in malignant melanoma (MM), being associated with tumor invasive phase, metastases, and more aggressive neoplastic phenotypes. AIM: The main objective of the current study was to correlate the expression of the MMPs with the evolution of MM toward distant metastasis. PATIENTS, MATERIALS AND METHODS: We designed a retrospective cohort study, including 13 patients with metastatic MM. Data concerning age, sex, localization of the primary lesion and metastasis, and histological and immunohistochemical features (intensity of expression and percent of positive cells for MMPs) were statistically processed. RESULTS: The time between the diagnosis of primitive melanoma and the diagnosis of metastasis ranged between 0 and 73 months, with a mean value of 18.3 months. The metastases rich in MMP1- and MMP9-positive cells occurred earlier than the metastases with low levels of positive cells. The mean period until metastasis was shorter for the MMP1-expressing tumors than the ones without MMP1 expression. MMP13 expression in the tumor and its metastasis was significantly linked with the time until the metastasis occurrence. CONCLUSIONS: This study emphasizes the roles of MMP1, MMP9, and MMP13 in the process of metastasis in melanoma and the opportunity to use them as therapeutic targets and surveillance molecules.

Pharmacotechnical, Physico-Chemical, and Antioxidant Evaluation of Newly Developed Capsule Formulations.

The excess of free radicals causes numerous imbalances in the body that lead to premature aging, the degradation of internal structures, and the appearance of numerous pathologies responsible for the increased risk of premature death. The present work aims to evaluate the physical, chemical, pharmacotechnical, and antioxidant activity of newly achieved capsule formulations. These two formulations were F1a.i., which contains melatonin:biotin:coenzyme Q10 (weight ratio of 1:2:60), and F2a.i., which contains quercetin:resveratrol:biotin:coenzyme Q10 (weight ratio of 10:10:1:10). The adequate selection of the excipient types and amounts for final capsule formulations (F1c.c., F2c.c.) was based on preformulation studies performed on the powders containing active ingredients. The antioxidant activity assessed using three methods (ABTS, DPPH, and FRAP) compared with acid ascorbic as a positive control demonstrated that the F2c.c. formulation possesses the strongest antioxidant capacity. The results confirmed the suitable formulation and the accurate selection of the types and amounts of active ingredients, as well as the auxiliary excipients used in newly developed capsule formulations as supplements with an excellent antioxidant effect on the human body.

Plasma Derived Products for Polypropylene Mesh Integration in Abdominal Wall Defects: Procedure Description and Partial Results.

Introduction: Abdominal wall surgery for parietal defects is done by implanting a type of mesh in the surrounding tissue above or beneath the fascia layer of the abdominal wall. The most common type of mesh used is polypropylene which sometimes takes a lot of time to be covered by the fibrous tissue. In an attempt to accelerate the cellular binding on the mesh and so to increase the recovery rate, we developed a protocol with plasma derived products to accelerate the mesh integration. Platelet rich fibrin (PRF) and platelet rich plasma (PRP) were evaluated in promoting the collagen synthesis and cell proliferation on the mesh surface. Material and Methods: We evaluated 32 patients with different types of abdominal wall defects which required polypropylene mesh implants in open surgery with the mesh implanted above the aponeurosis layer. We divided the patients into 3 groups: standard procedure, mesh augmented with PRF only, mesh augmented with PRP only. Results: Even though the number of patients involved in the study has a very small impact for a statistical analysis, the pattern observed in our prospective study reveals from the beginning that augmenting the standard procedure with plasma derived products improve the outcome (mesh integration) up to 65% faster integration. Conclusion: The technique that we used to augment the standard implant is cost-effective and simple to use in the surgical theatre.

Dietary Anthocyanins and Stroke: A Review of Pharmacokinetic and Pharmacodynamic Studies.

Cerebrovascular accidents are currently the second major cause of death and the third leading cause of disability in the world, according to the World Health Organization (WHO), which has provided protocols for stroke prevention. Although there is a multitude of studies on the health benefits associated with anthocyanin (ACN) consumption, there is no a rigorous systematization of the data linking dietary ACN with stroke prevention. This review is intended to present data from epidemiological, in vitro, in vivo, and clinical studies dealing with the stroke related to ACN-rich diets or ACN supplements, along with possible mechanisms of action revealed by pharmacokinetic studies, including ACN passage through the blood-brain barrier (BBB).

Novel perspectives on gastrointestinal stromal tumors (GISTs).

Since they were described, gastrointestinal stromal tumors (GISTs) are, for pathologists and not only for them, a subject of controversy regarding histological origin, differentiation, nomenclature, malignant potential and prognosis. Before 1998, there were no certainties that GISTs were fundamentally different from other types of abdominal cancers in the big family of mesenchymal tumors. Before the discovery of KIT gene mutations, GISTs were most often classified as leiomyoma, leiomyosarcoma, leiomyoblastoma, and gastrointestinal autonomic nerve tumor. When a tumor is discovered, the first data obtained are initially assessed by one or more imaging tests, such as an ultrasound, computed tomography scan or magnetic resonance imaging. The imaging results define the size of the lesion and its anatomic location, which in the case of GIST is usually within the wall of the stomach or intestine. Depending on the experience of the medical team - radiologist, gastroenterologist or surgeon - reviewing the imagistic tests and correlating them with the general patient profile, the differential diagnostic is reduced and GIST may become the main suspect.

Morphological, imaging and surgical aspects in a complex case of uterine leiomyosarcoma - case report and review of the literature.

Leiomyosarcoma is a rare condition so there are relatively few and small case series and no prospective studies to provide clear guidelines regarding management. We report on a case that presents some particularities that further underline diagnostic and treatment difficulties posed by the affliction of such a rare tumor. This is the case of a 43-year-old woman who had a large tumor arising from the uterus, with a spectacular growth rate over a short period. The patient, with congenital spastic tetraparesis and hydrocephalus, came for belly enlargement with rapid increase in size over the previous two months. Physical exam and ultrasound lead to the conclusion of a large abdominal mass. A computed tomography scan showed a mass arising from the pelvis and a large amount of ascites. An exploratory laparotomy was performed and the histopathology report confirmed the diagnosis of uterine leiomyosarcoma. Leiomyosarcoma poses challenging problems regarding histological grading and, due to its rate of growth, real surgical difficulties. Final diagnosis is done by histopathological examination after surgical excision. Frequently, it is late diagnosed when complete removal of the tumor is often impossible.

Paraoxonase 1 - an Update of the Antioxidant Properties of High- Density Lipoproteins.

Paraoxonase 1 (PON1) belongs to a family of enzymes with related functions, being the best studied member. PON1 is a HDL-associated protein of which function is to protect LDL particles from oxidative modifications. The status of PON1 is influenced by different genetic, life style and dietary factors. This short review is aimed to present some new aspects regarding the antioxidant properties of PON1 with emphasis on the influence exerted by different factors. Also, a special attention is paid to the relationship between PON1 and low- and high-density lipoproteins in the context of atherosclerosis which affects the endothelial cells.

Testing five social-cognitive models to explain predictors of personal oral health behaviours and intention to improve them.

PURPOSE: To test the ability of several social-cognitive models to explain current behaviour and to predict intentions to engage in three different health behaviours (toothbrushing, flossing and mouthrinsing). MATERIALS AND METHODS: Constructs from the health belief model (HBM), theory of reasoned action (TRA), theory of planned behaviour (TPB) and the motivational process of the health action process approach (HAPA) were measured simultaneously in an undergraduate student sample of 172 first-year medical students. RESULTS: Regarding toothbrushing, the TRA, TPB, HBM (without the inclusion of self-efficacy SE), HBM+SE and HAPA predictor models explained 7.4%, 22.7%, 10%, 10.2% and 10.1%, respectively, of the variance in behaviour and 7.5%, 25.6%, 12.1%, 17.5% and 17.2%, respectively, in intention. Regarding dental flossing, the TRA, TPB, HBM, HBM+SE and HAPA predictor models explained 39%, 50.6, 24.1%, 25.4% and 27.7%, respectively, of the variance in behaviour and 39.4%, 52.7%, 33.7%, 35.9% and 43.2%, respectively, in intention. Regarding mouthrinsing, the TRA, TPB, HBM, HBM+SE and HAPA predictor models explained 43.9%, 45.1%, 20%, 29% and 36%, respectively, of the variance in behaviour and 58%, 59.3%, 49.2%, 59.8% and 66.2%, respectively, in intention. The individual significant predictors for current behaviour were attitudes, barriers and outcome expectancy. CONCLUSION: Our findings revealed that the theory of planned behaviours and the health action process approach were the best predictor of intentions to engage in both behaviours.

The relationship between alanerv(®) consumption and erythrocytes' redox status in post-acute stroke patients undergoing rehabilitation.

OBJECTIVES: Stroke is a pathological condition associated with a redox imbalance. Both the acute and the post-acute phases after a stroke are characterized by a pro-oxidant state, which could be corrected through antioxidant supplementation. The aim of the present study was to evaluate the effect of the ALAnerv(®) upon the redox status of erythrocytes. MATERIAL AND METHODS: For this pilot study were enrolled 28 post-acute stroke patients. They were randomly divided into a control group [(-) ALA] and a study group [(+) ALA]. Patients were hospitalized for a period of two weeks. Blood samples were taken at the beginning and at the end of this period. Patients from (+) ALA group received the nutritional supplement ALAnerv(®). Catalase, SOD, GPx, GRed and GT activities were assessed on erythrocytes' lysates. Also, the total antioxidant capacity as well as the concentration of total thiols were evaluated. OUTCOMES: During the study period only SOD (1393.48 ± 69.14 U/g Hb vs. 1514.06 ± 60.80) and GRed (4.47 ± 0.37 U/g Hb vs. 5.06 ± 0.24) significantly increased in (+) ALA group. Catalase (173.70 ± 14.62 k/g Hb vs. 123.41 ± 8.71) and GT (5.55 ± 0.26 U/g Hb vs. 4.95 ± 0.23) activities significantly decreased during the study period. Multiple regression indicated that only SOD, GT and GRed activities were influenced by the ALAnerv(®) consumption. There was no significant increase if the total thiols concentration. CONCLUSIONS: ALAnerv(®) consumption could be associated with a correction of the erythrocytes' redox status. There is a need to investigate if administration of ALAnerv(®) over a longer time period could have a more significant influence on the erythrocytes' antioxidant system.

The consumption of alanerv® nutritional supplement and the dynamic of some inflammatory markers in post-acute stroke patients undergoing rehabilitation.

OBJECTIVES: Stroke is followed by an inflammatory response lasting up to several months. Moreover, many of the stroke-related comorbidities (i.e., diabetes mellitus, dyslipidemia, cardiovascular disease, and atherosclerosis) are characterized by an pro-inflammatory status. MATERIAL AND METHODS: We designed this pilot study to evaluate the relation between the consumption of a nutritional supplement (ALAnerv®) and the dynamic of the inflammatory status in post-acute stroke patients undergoing rehabilitation. The study population comprised 28 patients which were assigned into two study groups, named (-) ALA and (+) ALA. All subjects followed the same rehabilitation program. There were no significant differences in respect to the standard medication between the groups. Moreover, patients from the (+) ALA group received ALAnerv® for two weeks (2 pills/day). We assessed IL-1α, IL-6, TNF-α, sICAM-1, and myeloperoxidase in blood samples taken at the beginning and at the end of the study period. OUTCOMES: In the (+) ALA group only IL-1α (- 9.9% ± 3.7, P = 0.013) and IL-6 (- 26.5% ± 8.2, P = 0.003) significantly decreased during the study period. The multiple regression analysis indicated that the ALAnerv® treatment was responsible for the significant decrease of IL-6 level (P = 0.008). Moreover, the percentage of IL-6 variation between the study groups reached statistical significance (8.4% ± 11.5 vs. - 26.5% ± 8.2, P = 0.034). CONCLUSIONS: These results indicate that ALAnerv® could be beneficial for the correction of the inflammatory status in post-acute stroke patients and underline the need of a longer treatment period with a higher dose.

The Relationship Between Alanerv(®) Consumption and Erythrocytes' Glyoxalases I and II Activities and The Level of Some Serum Markers of Carbonyl Stress in Post-Acute Stroke Patients Undergoing Rehabilitation.

OBJECTIVES: Diabetes mellitus is one of the most frequent stroke-related comorbid states, and it is characterized by accumulation of reactive carbonyl compounds (RCOs), leading to "carbonyl stress". This pilot study was aimed to evaluate the effect of the consumption of the nutritional supplement ALAnerv(®) on some serum carbonyl stress markers, as well as on the activity of erythrocytes' glyoxalases in post-acute stroke patients undergoing rehabilitation. MATERIAL AND METHODS: We created a study population of 28 patients, organized into (-) ALA and (+) ALA groups. Patients from (+) ALA group received ALAnerv(®) for two weeks (2 pills/day). All the subjects followed the same rehabilitation program. In both groups, blood samples were taken at the hospitalization and at the discharge moments, respectively. On these samples we assessed lactic acid, fructosamine and RCOs concentrations, as well as the activities of glyoxalases 1 and 2 from erythrocytes' lysates. OUTCOMES: In (-) ALA group the concentrations of fructosamine and RCOs significantly increased (0.90 ± 0.04 vs. 1.02 ± 0.04, p = 0.020; 0.19 ± 0.03 vs. 0.28 ± 0.07, p = 0.027) during the study period. Also, glyoxalase 2 activity decreased in this group (27.04 ± 6.10 vs. 14.43 ± 3.02, p = 0.027). In (+) ALA group, the variation of these parameters did not reach statistical significance. Only, the activity of Glo1, which catalyzes the rate-limiting step in the glyoxalase pathway, had an increasing trend in (+) ALA group. The percentage of variation of fructosamine between (-) ALA and (+) ALA groups reached statistical significance (14.8 ± 5.2 vs. - 1.0 ± 13.3, p = 0.047). Regression analysis indicated that the activity of glyoxalase 2 was significantly influenced by the treatment with ALAnerv(®) (p < 0.001), while the concentration of RCOs was significantly influenced by diabetes mellitus (p = 0.030). CONCLUSIONS: Our preliminary results suggest that ALAnerv(®) could be useful for the correction of the carbonyl stress status in post-acute stroke patients with diabetes. Also, this study underlines the need of a longer treatment period with a higher dose.

Paraoxonases as protective agents against N-acyl homoserine lactone - producing pathogenic microorganisms.

ABSTRACT: Paraoxonases are a group of enzymes with a high "substrate-promiscuity", being able to act on many structurally different compounds. To date, there is no consensus regarding the physiological substrate(s) of these enzymes. Recent data suggest that the N-acyl homoserine lactones (AHLs) produced by different Gram-negative bacteria, including the opportunistic Pseudomonas aeruginosa, could be such substrates. Due to the ability of paraoxonases to hydrolyze AHLs, they represent an alternative mechanism of protection against pathogen microorganisms, interfering with the quorum sensing systems that allow these bacteria to respond in a coordinate manner to different changes in the extracellular environment. This mini-review presents some novel aspects regarding the relationship between paraoxonases and the aforementioned compounds, highlighting the potential role of these enzymes as a component of the humoral innate defence system.

Effect of the nutritional supplement ALAnerv® on the serum PON1 activity in post-acute stroke patients.

BACKGROUND: Paraoxonase-1 (PON1) is one of the HDL-associated proteins which contributes to the antioxidant properties of these lipoproteins. The aim of this pilot study was to evaluate the effect of the nutritional supplement ALAnerv® on serum PON1 activity in post-acute stroke patients undergoing rehabilitation. METHODS: We enrolled 28 post-acute stroke patients and randomly divided them into (-) ALA or (+) ALA study groups. All the patients underwent the same rehabilitation program and received comparable standard medications. Moreover, (+) ALA patients received ALAnerv® for two weeks (2 pills/day). The serum PON1 activity was assessed on blood samples taken at the admission and at the discharge moments, respectively. We used paraoxon (paraoxonase activity, PONA), phenyl acetate (arylesterase activity, ARYLA) and dihydrocoumarin (lactonase activity, LACTA) as substrates, the latter activity being regarded as physiologically relevant. A control group of 14 apparently healthy subjects was also created. RESULTS: In the (+) ALA group, LACTA significantly increased during the study period (17.6 ± 3.2 vs. 27.6 ± 3.5, p = 0.002). Moreover, the percentage of LACTA variation between (-) ALA and (+) ALA groups during the study was also statistically different (-11.7 ± 6.9% vs. +95.1 ± 29.7%, p < 0.0001). CONCLUSIONS: These preliminary results suggest that ALA nerv® could contribute to the improvement of the physiologically relevant LACTA of PON1 in post-acute stroke patients, enabling this enzyme to contribute to the redox correction. Also, this study raises the question about the effect of a longer treatment period over the other enzymatic activities of serum PON1.

Predicting undergraduates' intentions to improve oral health behaviors: the importance of self-identity--a pilot study.

PURPOSE: The purpose of this study was to explore the predictive ability of factors associated with the Theory of Planned Behavior (TPB) on oral health behaviors. METHODS: The participants of this descriptive, cross-sectional study were 179 first year medical students at the Carol Davila University of Medicine and Pharmacy that completed a questionnaire assessing TPB variables, self-identity and their current oral hygiene behaviors. RESULTS: Significant differences in self-identity regarding the toothbrushing behavior and reason for the dental visit were observed (p < 0.0001). When participants were classified in 2 groups according to their levels of self-identity, significant differences were found according to their age, toothbrushing frequency, attitudes, perceived behavioral control and intention for improving oral hygiene (p < 0.0001). Self-identity had a statistically significant positive correlation with affective attitudes, cognitive attitudes, subjective norms, perceived behavioral control and intention for improving oral hygiene. Hierarchical multiple regressions for toothbrushing frequency revealed that the TPB factors and self-identity explained 31% and 35% from the intention to improving behaviors, the coefficients for self-identity being significant. The structural equation model revealed the effect of self-identity on intention on improving oral health behaviors and the effect of past-behavior on self-identity. CONCLUSION: The findings revealed the value of the extended TPB model as a predictor of intention to improve oral health behaviors. Dental educators should focus on issues of students' self-identity as a person concerned by their oral health.

The effect of the ALAnerv nutritional supplement on some oxidative stress markers in postacute stroke patients undergoing rehabilitation.

Stroke is a pathologic condition associated with redox imbalance. This pilot study was designed to evaluate the effect of the consumption of the nutritional supplement ALAnerv on some oxidative stress markers in postacute stroke patients undergoing rehabilitation. To achieve this goal, we assigned 28 patients to 2 study groups: (-)ALA and (+)ALA. Patients in both groups participated in the same rehabilitation program and received comparable standard medications; however, patients in the (+)ALA group received ALAnerv for 2 weeks (2 pills per day). We assessed total and nonproteic thiols, protein carbonyls, ceruloplasmin, oxidized low-density lipoprotein (LDL) particles, lipid hydroperoxide concentrations, gamma-glutamyl transpeptidase activity, and total antioxidant capacity. Regression analysis indicated that supplementation with ALAnerv was responsible for the significant decrease in glucose (p = 0.002) and oxidized LDL particles (p < 0.001) during the study period. For both parameters, the variation in the percent of concentration between the 2 groups during the study period reached statistical significance (p = 0.012 and p < 0.001, respectively). Moreover, Barthel Index values at discharge were significantly influenced by ALAnerv treatment. These preliminary results indicate that ALAnerv might be helpful because it rapidly corrects plasma fasting glucose and corrects serum oxidized LDL particle concentrations, suggesting the need for longer treatment with 2 pills or more per day.

New approach to identify ischemic stroke patients at risk to develop hemorrhagic transformation.

Some patients with ischemic stroke are subject to hemorrhagic transformation, a complication leading to increased patient morbidity and mortality. The discovery of biomarkers that can be used to identify ischemic strokes prone to this complication are very important for the clinical practice because therapy could be altered to mitigate the risk. We discuss here the results of a trial that evaluated for the first time tight junction proteins as biomarkers of blood-brain barrier disruption and hemorrhagic transformation in ischemic stroke.

Modeling the theory of planned behavior for intention to improve oral health behaviors: the impact of attitudes, knowledge, and current behavior.

The aim of this study was to test the efficiency of an extended model of the theory of planned behavior (TPB) in predicting intention to improve oral health behaviors. The participants in this cross-sectional study were 153 first-year medical students (mean age 20.16, 50 males and 103 females) who completed a questionnaire assessing intentions, attitudes, subjective norms, perceived behavioral control, oral health knowledge, and current oral hygiene behaviors. Attitudes toward oral health behaviors and perceived behavioral control contributed to the model for predicting intention, whereas subjective norms did not. Attitudes toward oral health behaviors were slightly more important than perceived behavioral control in predicting intention. Oral health knowledge significantly affected affective and cognitive attitudes, while current behavior was not a significant predictor of intention to improve oral health behavior. The model had a slightly better fit among females than among males, but was similar for home and professional dental health care. Our findings revealed that attitude, perceived behavioral control, and oral health knowledge are predictors of intention to improve oral health behaviors. These findings may help both dentists and dental hygienists in educating patients in oral health and changing patients' oral hygiene habits.

Dynamic of oxidative and nitrosative stress markers during the convalescent period of stroke patients undergoing rehabilitation.

BACKGROUND: Stroke patients have a redox imbalance, a consequence of both the cerebrovascular event and the associated pathological conditions. Our study was aimed to investigate the dynamic of some oxidative and nitrosative markers during the convalescent phase of postacute stroke patients undergoing rehabilitation. METHODS: We assessed thiol, advanced oxidation protein product, protein carbonyl, 3-nitro-l-tyrosine, ceruloplasmin and oxidized LDL concentrations, as well as gamma-glutamyltranspeptidase (GGT) activity in 20 patients at the beginning of the hospitalization and at the discharge moment, respectively, and 24 apparently healthy controls. RESULTS: We found significantly increased values for GGT (P = 0.04), ceruloplasmin (P = 0.01) and protein carbonyl (P = 0.04) in stroke patients at the hospitalization moment when compared with healthy controls, while total thiols were significantly decreased (P = 0.002). Rehabilitation was associated with a significant decrease of protein carbonyl (P = 0.03) and oxidized LDL particle concentrations (P = 0.03), as well as GGT activity (P = 0.02). At the hospitalization moment, both GGT and ceruloplasmin were significantly negatively correlated with non-proteic thiols (r = -0.44, P = 0.049, and r = -0.53, P = 0.015, respectively) and significantly positively with protein carbonyls (r = +0.80, P < 0.001, and r = +0.69, P < 0.001, respectively) suggesting putative roles of GGT and ceruloplasmin in the redox imbalance. CONCLUSIONS: These results highlight the existence of a redox imbalance in postacute stroke patients, and the possible benefits of an antioxidant-based therapy for the recovery of these patients.