Plasma Concentrations of Rosmarinic Acid in Patients on Antiretroviral Therapy: In Silico Exploration Based on Clinical Data.

Rosmarinic acid (RA) is a phenolic compound with antiviral properties, often encountered in dietary supplements and herbal drugs. Data on the pharmacokinetics of RA are lacking in cases of the chronic use of supplements containing this compound, and only limited data on the metabolism and distribution of RA are available. The aim of the study was to investigate the plasma levels of RA after 12 weeks of use and determine potential interactions of RA and selected antiretroviral drugs. Patients infected with human immunodeficiency virus took a supplement containing RA for 12 weeks, after which the RA concentrations in the plasma samples were analyzed. A detailed in silico analysis was conducted in order to elucidate the potential interactions between RA and the drugs efavirenz, darunavir and raltegravir. It was found that RA can be detected in patients' plasma samples, mainly in the form of sulphoglucuronide. The potential interactions are suggested on the level of liver metabolizing enzymes and efflux P-glycoprotein, with RA competing with antiretroviral drugs as a substrate in metabolism and distribution systems. The present study suggests that the simultaneous use of RA and antiretroviral therapy (containing efavirenz, darunavir or raltegravir) may affect the plasma levels of RA after prolonged supplementation.

Supercritical fluid technology as a strategy for nifedipine solid dispersions formulation: In vitro and in vivo evaluation.

Supercritical fluid technology (SFT) is an insufficiently investigated approach for the production of solid dispersions, it is environmentally acceptable and has a high potential for application in the pharmaceutical industry. The aim of this work was to formulate and characterize nifedipine solid dispersions (SDs) produced by the SFT and compare the results with ones obtained by the classical solvent based kneading method. The following in vitro tests were conducted: assay and yield, solvent residues, solid state characterization (FTIR, DSC, XRD), flowability, hygroscopicity, solubility, dissolution and stability. Additionally, bioavailability was examined on an animal model (Wistar rats). The formulation selection for in vivo study was performed using the multilevel categoric experimental design and the health risk assessment. Solid state characterization revealed that formulation obtained by the SFT method and higher ratio of polymer (1:5) have had nifedipine in completely amorphous form. Polymer ratio and method of SDs preparation do influence the investigation characteristics. Dissolution rate was fastest in SDs prepared by the SFT and higher polymer ration (1:5). In vivo data of selected SDs prepared by the kneading (ratio 1:1) and the SFT (ratio 1:5) showed alteration in pharmacokinetic profile after i.v. and p.o. application.

Health risk assessment of ethyl carbamate in fruit spirits.

Alcoholic beverages are multicomponent mixtures containing several carcinogenic compounds, including ethyl carbamate, which was evaluated in fruit spirits against the limit proposed by the International Alliance for Responsible Drinking (IARD) and then in terms of associated health. It was above the limit in 40% of the samples and statistically higher in stone fruit spirits. The MOE values below the limit were obtained for 49% and 98% of the samples at average and chronic heavy consumption by men, while for women the limit was reached by 19% and 96% of the samples, respectively. The lifetime cancer risk (LCR) approach based on the oral slope factor indicated risk concern for 96% of the samples at average consumption, regardless of gender, while LCR based on virtually safe dose indicated 25% and 69% of the samples posing a risk to women's and men's health, respectively. Preventive measures during spirit production and legal regulation of ethyl carbamate should be considered.

Biological Activity of Genus Hypericum Sect. Hypericum Species-H. tetrapterum, H. maculatum subsp. immaculatum, H. triquetrifolium.

St. John's wort (Hypericum perforatum, Hypericaceae) has long been used in traditional medicine as a potent remedy, while many other species of this genus have not been thoroughly investigated. The study aimed to detect the biological activity, including antioxidant, antihyperglycemic, anticholinergic, antimicrobial and monoaminoxidase inhibitory potential, of water-alcoholic extracts of three species autochthonous for Serbia and Greece from plant genus Hypericum (section Hypericum-H. tetrapterum, H. maculatum ssp. immaculatum and H. triquetrifolium), followed by phytochemical profiling. The highest amount of phenolics was recorded in H. maculatum subsp. immaculatum extract, while the highest abundance of flavonoids was characteristic of H. tetrapterum extract. Hypericin and hyperforin, quercetin, and its flavonoid, rutin, were present in all of the evaluated species. The evaluated species were good scavengers of DPPH, OH and NO radicals, as well as potent reducers of ferric ions in FRAP assay. Furthermore, the evaluated species were shown as potent inhibitors of monoaminoxidase A and α-glucosidase and modest inhibitors of acetylcholinesterase, monoaminoxidase B and α-amylase. No anti-Candida activity was recorded, but the extracts were effective against MRSA Staphylococcus aureus and Enterococcus sp., as well as against Proteus mirabilis. The obtained results strongly highlight the need for further in vivo studies in order to better define the potential of the medicinal application of the studied species.

Safety Assessment of Herbal Food Supplements: Elemental Profiling and Associated Risk.

Increased usage of herbal food supplements by both the paediatric and adult populations prompted a health risk assessment study. The elemental profiles of 52 supplements collected in Serbia were obtained using ICP-MS. The calculated contribution to permitted daily exposure was in compliance with the guidelines for elemental impurities: up to 46.8% for Pb (infants), 67.2% for Cu (toddlers), 6.8% for As (preschool children), and 8.0% for Hg (adolescents). Hazard quotients indicated high exposure of toddlers to Cu (100.9%) and Zn (112.7%), although by only one supplement, for which hazard indices ranged from 229 to 105% (aligning from toddlers to adolescents). Based on the margin of exposure, As and Pb were not of safety concern. Conversely, the proportion of supplements exceeding the acceptable level of lifetime cancer risk due to As exposure varied from 41.9% in adolescents to 54.3% in adults. Simultaneous use of multiple supplements over a prolonged period of time could further deepen health concerns.

Comparative Health Risk Assessment of Heated Tobacco Products versus Conventional Cigarettes.

BACKGROUND: Smoking is the largest preventable cause of death in the world with around eight million estimated premature deaths per year. In response to the harmful effects of conventional tobacco products the tobacco industry has launched a new type of products called Heated tobacco products (HTP) and e-cigarettes, which are considered safer for human health than conventional cigarettes. MATERIALS AND METHODS: The research was conducted by searching the scientific literature using platforms "Google scholar," "PubMed" and "Science Direct." To compare the non-carcinogenic and carcinogenic risk of HTP products and conventional cigarettes, margin of exposure and lifetime excess cancer risk were calculated using data obtained from a scientific literature search.HTP products have shown a reduced risk to human health compared to the conventional cigarettes, although they still contain compounds that can be dangerous to human health. There is not enough data obtained from independent studies that could safely indicate that these reduced amounts of toxic chemical entities in the composition of HTP do not induce any harmful effect. CONCLUSION: Further research is needed to determine the harmful effects of HTP aerosol, as well as to tighten the legislation that would limit the production, import and distribution of these products worldwide until their safety for human health is confirmed with a sufficient number of transparent and representative results obtained in independent scientific studies.

Phytochemistry and Antihyperglycemic Potential of Cistus salviifolius L., Cistaceae.

Cistus salviifolius has been previously reported as a traditional remedy for hyperglycemia. However, the plant has been scarcely investigated from scientific point of view. Thus, the aim was to examine the chemical composition and to evaluate its antioxidant and antihyperglycemic potential in vitro. Aqueous and ethanolic extracts were evaluated for total phenolic, tannin, and flavonoid content using spectrophotometric methods. Detailed chemical characterization was performed by high-performance liquid chromatography (HPLC-DAD). The volatile organic compounds (VOCs) profile was assessed by gas chromatography technique. The potential in diabetes treatment was evaluated through tests of free radicals neutralization, inhibition of lipid peroxidation process, and test of ferric ion reduction; activity in tests of inhibition of α-amylase, α-glucosidase and dipeptidyl peptidase-4 was also evaluated. High content of phenolics (majority being tannins) was detected; detailed HPLC analysis revealed high content of gallic acid, followed by rutin, chlorogenic and caffeic acids. The VOCs analysis determined sesquiterpene hydrocarbons and oxygenated sesquiterpenes as the main groups of compounds. The assays classified extracts as potent neutralizers of 2,2-diphenyl-1-picrylhydrazil and nitroso radicals formation and potent inhibitors of α-amylase and α-glucosidase. In conclusion, Cistus salviifolius represents a rich source of phenolics and essential oil with sesquiterpenes. The established results suggested its promising antioxidant and antihyperglycemic activities.

The Oxidative Stress Parameters as Useful Tools in Evaluating the DNA Damage and Changes in the Complete Blood Count in Hospital Workers Exposed to Low Doses of Antineoplastic Drugs and Ionizing Radiation.

Hospital workers at the Oncology Department are occupationally exposed to antineoplastic drugs (ANTNP) or low doses of ionizing radiation (Irrad). Therefore, the aim of this study was to evaluate the level of DNA damage, the oxidative stress parameters and complete blood count (CBC) of hospital workers in order to analyze the negative health effects of ANTNP and low dose Irrad. The frequency of micronuclei (MN) and proliferation index (PI) were analyzed by cytokinesis-block test. The oxidative stress biomarkers evaluated were the level of lipid peroxidation in plasma and catalase activity (CAT) in erythrocytes. A group of 86 hospital workers (35 exposed to ANTPN and 51 to Irrad) had increased MN frequency, CAT activity and level of lipid peroxidation compared to the control group, which consisted of 24 volunteers. The hemoglobin level was lower in the ANTNP group compared to thecontrol group, while a significant difference in RBC was recorded between thecontrol and Irrad groups, and in platelet count betweentheIrrad and ANTNP group. The results showed increased DNA damage, oxidative stress parameters, as well as impairment on complete blood count in hospital workers occupationally exposed to antineoplastic drugs and low-dose ionizing radiation. As this research has shown the importance of oxidative stress, we suggest that in addition to routine methods in periodic medical evaluation, the possibility of applying oxidative stress parameters is considered. Moreover, hospital workers exposed to ANTNP and Irrad in the workplace should undergo not only a more complete health prevention procedure but also have a more appropriate health promotion.

Garlic burn injuries- a systematic review of reported cases.

Medicinal plants have many beneficial effects on human health. Garlic (Allium sativum, Alliaceae) is one of the most famous herbal species, used for various diseases and conditions. Unfortunately, garlic is also associated with adverse effects, including cutaneous manifestations. In this review, burn injuries caused by application of raw garlic are reported. Searching through PubMed, Google Scholar and ResearchGate, a total of 32 articles with 39 patients were found. Demographics of patients, reasons for garlic use, details on garlic application, as well as description of burns and its treatment are thoroughly described and discussed. In most of the cases, garlic caused second-degree burns, although some circumstances can cause formation of necrotic tissue. Various body parts were affected, legs being most common. The chemistry of garlic is also presented, with focus on volatile organic sulfur compounds, which also seem to be responsible for burns formation. Treatment of garlic burns was mainly symptomatic, and various types of drugs were used. Although not commonly expected, garlic should be taken into consideration as causative agents of burns by treating doctors, and patients should be advised against application of fresh garlic onto skin and mucosa.