Biochemical Aspects That Lead to Abusive Use of Trimetazidine in Performance Athletes: A Mini-Review.

Trimetazidine (TMZ), used for treating stable angina pectoris, has garnered attention in the realm of sports due to its potential performance-enhancing properties, and the World Anti-Doping Agency (WADA) has classified TMZ on the S4 list of prohibited substances since 2014. The purpose of this narrative mini-review is to emphasize the biochemical aspects underlying the abusive use of TMZ among athletes as a metabolic modulator of cardiac energy metabolism. The myocardium's ability to adapt its energy substrate utilization between glucose and fatty acids is crucial for maintaining cardiac function under various conditions, such as rest, moderate exercise, and intense effort. TMZ acts as a partial inhibitor of fatty acid oxidation by inhibiting 3-ketoacyl-CoA thiolase (KAT), shifting energy production from long-chain fatty acids to glucose, reducing oxygen consumption, improving cardiac function, and enhancing exercise capacity. Furthermore, TMZ modulates pyruvate dehydrogenase (PDH) activity, promoting glucose oxidation while lowering lactate production, and ultimately stabilizing myocardial function. TMZs role in reducing oxidative stress is notable, as it activates antioxidant enzymes like glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). In conclusion, TMZs biochemical mechanisms make it an attractive but controversial option for athletes seeking a competitive edge.

Fennel Essential Oil as a Complementary Therapy in the Management of Diabetes.

Diabetes is a serious pathology that affects a significant number of people worldwide. Its progression is rapid and leads to serious complications if glycemic control is missing. The micro and macrovascular complications of diabetes produce disabilities over time that affect the daily lives of patients. The major challenge of diabetes therapy is to reach a stable glycemic state and to delay the onset of specific complications. Aromatherapy is considered an alternative or complementary therapy, but in recent years, there has been a tendency to overuse essential oils. The present study was designed to evaluate and compare the effects produced by the topical and oral administration of fennel essential oil to diabetic rats. Eighteen compounds in fennel essential oil were identified by gas chromatography-mass spectrometry (GC-MS) analysis. The major compounds were trans-anethole (64.6%) and fenchone (24.5%). The in vivo study revealed that after a four-week treatment with fennel essential oil, the rats' glycemic levels were significantly reduced (p ≤ 0.05). Furthermore, there were no differences between the two routes of administration. In addition, an ex vivo study underlined the potential effect of this essential oil in the prevention of cataract formation.

Potential Defence Mechanisms Triggered by Monosodium Glutamate Sub-Chronic Consumption in Two-Year-Old Wistar Rats.

Monosodium glutamate (MSG) is the sodium salt of glutamic acid (GLA), used as a flavour enhancer. MSG is considered a controversial substance. It is incriminated in disturbing the antioxidant system, but also has beneficial effects, as GLA metabolism plays a crucial role in homeostasis. This study highlights which positive or negative aspects of MSG sub-chronic consumption are better reflected in subjects potentially affected by advanced age. Daily doses of MSG were administered to four groups of two-year-old Wistar rats for 90 days: (I) 185 mg/kg bw, (II) 1500 mg/kg bw, (III) 3000 mg/kg bw and (IV) 6000 mg/kg bw, compared to a MSG non-consumer group. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, direct and total bilirubin, total cholesterol, triglycerides, creatinine and urea levels were analysed; stomach, liver and kidney samples were subjected to histopathological analysis. Although, in most cases, there were no statistical differences, interesting aspects of the dose-effect relationship were observed. After MSG sub-chronic consumption, the positive aspects of GLA seem to be reflected better than the negative ones. The hormesis effect, with low-level reactive oxygen species' protective effects and GLA metabolism, may represent the hypothesis of a potential defence mechanism triggered by MSG sub-chronic consumption in ageing rats.

LC-MS/MS assisted biomonitoring of ropivacaine and 3-OH-ropivacaine after plane block anesthesia for cardiac device implantation.

Introduction: Ropivacaine is a popular local anesthetic used for regional anesthesia or for pain management. Although designed as an enantiomerically pure drug, an aspect that reduces the adverse effects, its toxicological effects are still a risk. As such, biomonitoring to assure appropriate dosage and bioavailability are essential to avoid complications during or post-surgery. Methods: The study focused on developing a sensitive, selective, and accurate liquid chromatography-mass spectrometry (LCMS/MS) method which facilitates the biomonitoring of ropivacaine and its main metabolite in plasma after regional anesthesia using ropivacaine. Results and Discussion: The method was validated with regards to all relevant parameters, such as sensitivity, selectivity, accuracy, precision, and the effect of sample matrix. The method was successfully used in a pilot study, which included one patient undergoing plane block anesthesia for cardiac device implantation. The results showed the method is appropriate for its intended purpose and could even be used in other, similar applications.

The Lack of Standardization and Pharmacological Effect Limits the Potential Clinical Usefulness of Phytosterols in Benign Prostatic Hyperplasia.

The prevalence of benign prostatic hyperplasia (BPH) markedly increases with age. Phytotherapeutic approaches have been developed over time owing to the adverse side effects of conventional medications such as 5-reductase inhibitors and α1-adrenergic receptor antagonists. Therefore, dietary supplements (DS) containing active compounds that benefit BPH are widely available. Phytosterols (PSs) are well recognized for their role in maintaining blood cholesterol levels; however, their potential in BPH treatment remains unexplored. This review aims to provide a general overview of the available data regarding the clinical evidence and a good understanding of the detailed pharmacological roles of PSs-induced activities at a molecular level in BPH. Furthermore, we will explore the authenticity of PSs content in DS used by patients with BPH compared to the current legislation and appropriate analytical methods for tracking DS containing PSs. The results showed that PSs might be a useful pharmacological treatment option for men with mild to moderate BPH, but the lack of standardized extracts linked with the regulation of DS containing PSs and experimental evidence to elucidate the mechanisms of action limit the use of PSs in BPH. Moreover, the results suggest multiple research directions in this field.

Benzydamine-An Affordable Over-the-Counter Drug with Psychoactive Properties-From Chemical Structure to Possible Pharmacological Properties.

Benzydamine is a non-steroidal anti-inflammatory drug with distinct pharmacological properties from other compounds in the same therapeutic class. The differences are structural and pharmacological in nature; the anti-inflammatory mechanism is not strictly explained by the ability to interfere with the synthesis of prostaglandins. The compound is used strictly in local inflammatory diseases (inflammation in the oral and vaginal mucosa). In addition to the therapeutic indications found in the summary of product characteristics (SPC), the compound is used, in high doses, as a psychotropic substance for oral administration, having similar properties to lysergic acid diethylamide (LSD). As an over-the-counter (OTC) compound, it is easy to obtain, and the consequences of using it for purposes other than those assumed by the manufacturer raise various concerns. The reasons are related to the pharmacodynamic and pharmaco-toxicological properties, since neither the mechanism of action nor the possible side effects that would result from systemic consumption, in high doses, even occasionally, have been fully elucidated. The present review aims to analyze the pharmacodynamic properties of benzydamine, starting from the chemical structure, by comparison with structurally similar compounds registered in therapy (as an anti-inflammatory or analgesic) or used for recreational purposes.

Caffeine and Its Antioxidant Properties-It Is All about Dose and Source.

Caffeine is the most frequently used substance with a central nervous system stimulant effect, but its consumption is most often due to the intake of foods and drinks that contain it (coffee, tea, chocolate, food supplements with plant extracts of Guarana, Mate herba, Cola nuts). Due to its innocuity, caffeine is a safe xanthine alkaloid for human consumption in a wide range of doses, being used for its central nervous stimulating effect, lipolytic and diuresis-enhancing properties, but also as a permitted ergogenic compound in athletes. In addition to the mechanisms that explain the effects of caffeine on the targeted organ, there are many proposed mechanisms by which this substance would have antioxidant effects. As such, its consumption prevents the occurrence/progression of certain neurodegenerative diseases as well as other medical conditions associated with increased levels of reactive oxygen or nitrogen species. However, most studies that have assessed the beneficial effects of caffeine have used pure caffeine. The question, therefore, arises whether the daily intake of caffeine from food or drink has similar benefits, considering that in foods or drinks with a high caffeine content, there are other substances that could interfere with this action, either by potentiating or decreasing its antioxidant capacity. Natural sources of caffeine often combine plant polyphenols (phenol-carboxylic acids, catechins) with known antioxidant effects; however, stimulant drinks and dietary supplements often contain sugars or artificial sweeteners that can significantly reduce the effects of caffeine on oxidative stress. The objective of this review is to clarify the effects of caffeine in modulating oxidative stress and assess these benefits, considering the source and the dose administered.

An Updated Systematic Review of Vaccinium myrtillus Leaves: Phytochemistry and Pharmacology.

Bilberry leaves are used in many countries in traditional medicine for treating a wide variety of diseases. Due to the high therapeutic potential of Vaccinium myrtillus (VM) leaves, this review aims to present the latest knowledge on the phytochemical profile, as well as the therapeutic effects of this herbal drug. The review was conducted according to the Prisma guidelines, and the scientific databases were searched using combinations of the following keywords: "Vaccinium myrtillus", "leaves", "bilberry". Recent research was focused on the influence of abiotic factors on the phytochemical composition, and it seems that there are significant differences between the herbal drugs collected from different countries. The phytochemical composition is correlated with the broad spectrum of pharmacological effects. The paper outlines the potent antimicrobial activity of VM extracts against multidrug-resistant bacterial strains, and also the pathways that are modulated by the unique "cocktail" of phytoconstituents in different metabolic alterations. Reviewing the research articles published in the last 10 years, it seems that bilberry leaves have been slightly forgotten, although their phytochemical and pharmacological characteristics are unique.

Profiling the Concentration of Reduced and Oxidized Glutathione in Rat Brain Using HPLC/DAD Chromatographic System.

This study aimed to develop a HPLC/DAD method in order to determine and quantify the reduced glutathione (GSH) and oxidized glutathione (GSSG) levels in rat brain. Due to the presence of the thiol group (-SH), GSH can interact with the Ellman's reagent (DTNB), with which it forms a reaction product through which the level of GSH can be quantified, using the DAD detection system. Chromatographic separation was achieved after a derivatization process by using a mobile phase acetonitrile (A) and phosphate buffer (20 mM, pH = 2.5) (B). The compounds of interest were detected at 330 nm using a chromatographic C8 column. The method of determination met the validation criteria, specified by the regulatory bodies. The applicability of the method was demonstrated in a chronic toxicology study of central nervous system (CNS), following different treatment regimens with haloperidol.

A Simple HPLC/DAD Method Validation for the Quantification of Malondialdehyde in Rodent's Brain.

In the present study, a HPLC/DAD method was set up to allow for the determination and quantification of malondialdehyde (MDA) in the brain of rodents (rats). Chromatographic separation was achieved on Supelcosil LC-18 (3 µm) SUPELCO Column 3.3 cm × 4.6 mm and Supelco Column Saver 0.5 µm filter by using a mobile phase acetonitrile (A) and phosphate buffer (20 mM, pH = 6) (B). Isocratic elution was 14% for (A) and 86% for (B). The injection volume (loop mode) was 100 µL with an analysis time of 1.5 min. Flow rate was set at 1 mL/min. The eluted compound was detected at 532 nm by a DAD detector by keeping the column oven at room temperature. The results indicated that the method has good linearity in the range of 0.2-20 µg/g. Both intra- and inter-day precision, expressed as RSD, were ≤15% and the accuracies ranged between ±15%. The lower limit of quantification (LLOQ), stability, and robustness were evaluated and satisfied the validation criteria. The method was successfully applied in a study of chronic toxicology following different treatment regimens with haloperidol and metformin.

Glutamate - A multifaceted molecule: Endogenous neurotransmitter, controversial food additive, design compound for anti-cancer drugs. A critical appraisal.

One of the most widely used flavour enhancers in the food industry is monosodium glutamate (MSG). MSG consumption has been on an upward trend, worrying in terms of potential toxic effects. This review is focused on the long-term toxicity of MSG and the experimental evidence that supports it. The article's primary purpose was to survey recently published data regarding the consumption of MSG within safe limits. The administered doses in animal models are very varied and have given rise to controversy. Also, the paper comprises pathways to lower MSG toxicity and highlight other underexploited biological effects, as anti-cancer potential. The administration of MSG, combined with various compounds, has been shown benefit against toxic effects. Several recent studies have identified a possible mechanism that recommends MSG and some derivatives as potential anti-cancer agents. New anti-cancer compounds based on the glutamic acid structure must be studied and further exploited. International regulations require harmonization of safe doses of MSG based on current scientific studies. Replacing MSG with other umami flavour enhancers may be a safer alternative for human health in the future. The biological consequences of MSG consumption or therapeutical administration have not been fully deciphered yet.

Medical Knowledge, Religious Beliefs, and Free Will: Attitudes and Opinions of Various Undergraduate Female Respondents Regarding Oral Contraception. A Questionnaire-Based Study.

The decision to use oral contraception varies and is based on several considerations: Personal reasons, the evaluation of the benefit/ risk ratio, and religious beliefs. In this research, a questionnaire was distributed to 422 female students from the George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mures, Romania (UMPhST Târgu Mureș, Romania), aged between 19 and 24 years old. The first endpoint of the study was to evaluate the use of hormonal contraception by the sexually active female population. The second endpoint was to assess the degree of awareness of the benefit/risk ratio of oral contraceptive use. The third endpoint was to evaluate the influence of religious beliefs regarding the decision to use this type of pharmaceutical product. Our results show that only a small percentage of students chose to use oral contraceptive pills (OCP). Fortunately, most of the respondents were well-informed and used a particular contraceptive drug based on a healthcare professional's recommendation. Another aspect that emphasizes the choice of contraceptive method is the religious affiliation, which could influence the decision to use OCP. For the students with medical knowledge, the advice of a healthcare professional seems to be quite important, because they are aware of the risks of improper use of OCP. Although religious doctrines affect the decision to use oral contraception, this is not always taken into account, as the use of OCP is a personal decision.

A Comprehensive Review of the Phytochemical, Pharmacological, and Toxicological Properties of Tribulus terrestris L.

The general spread of Tribulus terrestris L. (South Africa, Australia, Europe, and India), the high content of active ingredients (in particular sterol saponins, as well as flavonoids, tannins, terpenoids, phenol carboxylic acids, and alkaloids), and its frequent uses in folk medicine, and as food supplements highlight the importance of evaluating its phytopharmacological properties. There are miscellaneous hypotheses that the species could have a high potential for the prevention and improvement of various human conditions such as infertility, low sexual desire, diabetes, and inflammatory diseases. Worldwide, numerous herbal supplements are commercialized with indications mostly to improve libido, sexual performance in both sexes, and athletic performance. Phytochemical studies have shown great disparities in the content of active substances (in particular the concentration of furostanol and spirostanol saponoside, considered to be the predominant active ingredients related to the therapeutic action). Thus, studies of experimental pharmacology (in vitro studies and animal models in vivo) and clinical pharmacology (efficacy and safety clinical trials) have sometimes led to divergent results; moreover, the presumed pharmacodynamic mechanisms have yet to be confirmed by molecular biology studies. Given the differences observed in the composition, the plant organ used to obtain the extract, the need for selective extraction methods which are targeted at the class of phytocompounds, and the standardization of T. terrestris extracts is an absolute necessity. This review aims to highlight the phytochemical, pharmacological, and toxicological properties of T. terrestris, with a focus on the contradictory results obtained by the studies conducted worldwide.

With or Without Internal Standard in HPLC Bioanalysis. A Case Study.

The mandatory strategy of using internal standard in HPLC is still controversial. Despite that the introduction of internal standard methodology in the early stage of development of HPLC technology was used to improve method accuracy and precision, there are still practical situations in which a simple external standard quantification is adequate. The aim of the study is to compare the determination of meloxicam (MXC) in human plasma by HPLC with or without using an internal standard according to some key points related to the reason of introducing the internal standardization such as the reducing of sample preparation errors or variability for low injection volumes. The HPLC analysis was performed on reversed phase with UV detection after protein precipitation. Piroxicam (PXC) was used as an internal standard. The two methods are compared in terms of accuracy and precision over the same concentration range. The stability of the analyte has been proved. According to the results, the quantitative determination of MXC in human plasma after simple protein precipitation by using PXC as an internal standard does not bring any significant improvement of accuracy and precision of the experimental measurements.

HPLC Enantioseparation of ß-Blockers on Ovomucoid Stationary Phase†.

The purpose of this study was to separate single and multiple pairs of six ß-blockers enantiomers by high performance liquid chromatography on ovomucoid (OM) column in optimal conditions. The separation was performed isocratically or in gradient elution at 25°C, flow rate of 1 mL/min and 220 nm. The mobile phase consisted of phosphate buffer/acetonitrile or methanol. The effect of the organic modifier, the influence of pH and the percentage of the aqueous phase on resolution were investigated. The elution order of propranolol (PRP) enantiomers was established as well as the detection and quantification limits. The results show that OM was suitable for enantiomeric separation of the nonselective ß-blockers carvedilol, PRP, pindolol and oxprenolol, and not for the two ß-1 selective blockers, atenolol and metoprolol. A hypothesis regarding a possible correlation between structure-pharmacological activity-chromatographic behavior is proposed.