Anti-inflammatory and in vitro antioxidant activities of Satureja montana dry extract.

INTRODUCTION: Many chronic somatic and psychiatric diseases are associated with oxidative stress and inflammation, both of which have detrimental effects on human health.

Invasive pulmonary co-infection caused by Aspergillus sp. and Pneumocystis jirovecii, complicated by Cytomegalovirus reactivation in a patient following second allogeneic hematopoietic stem cell transplantation - Case report.

Invasive fungal infections are common complication in hematopoietic stem cell transplant recipients, often leading to high morbidity and mortality rates. Furthermore, when invasive fungal co-infections are diagnosed the prognosis is rarely favorable. Here, we present a rare case of a 47-year-old HIV-negative male with invasive pulmonary co-infection caused by Aspergillus sp. and Pneumocystis jirovecii, complicated by Cytomegalovirus reactivation following second allogeneic hematopoietic stem cell transplantation with a fatal outcome. 2012 Elsevier Ltd. All rights reserved.

Effect of Plant Extracts Combinations on TNF-α, IL-6 and IL-10 Levels in Serum of Rats Exposed to Acute and Chronic Stress.

Oxydative stress, anxiety and depression are associated with changes in cytokine levels. Natural products, including individual and combined plant extracts, have the potential to be used in the treatment of neuropsychiatric disorders. The goal of this study is to investigate the effects of two combined plant extracts, rich in flavonoids, on the levels of the cytokines TNF-α, IL-6, and IL-10 in rats subjected to models of acute cold stress and chronic unpredictable stress. The study utilized common medicinal plants such as Valeriana officinalis, Melissa officinalis, Crataegus monogyna, Hypericum perforatum, and Serratula coronata, which were combined in two unique combinations-Antistress I and Antistress II. The compositions of the used extracts were determined by HPLC methods. Pro- and anti-inflammatory cytokines in rats' serum were measured with Enzyme-linked immunosorbent assay. The results from the acute stress model revealed that the individual extract of Crataegus monogyna decreased levels of TNF-α, while Serratula coronata, Hypericum perforatum, and Valeriana officinalis effectively reduced IL-6 levels. Both combinations, Antistress I and Antistress II, were effective in reducing TNF-α and IL-6 levels, with Antistress II also increasing IL-10 levels. In the chronic stress model, Hypericum perforatum extract decreased the levels of the pro-inflammatory cytokines TNF-α and IL-6, whereas extracts of Serratula coronata and Valeriana officinalis only reduced TNF-α levels. The two combined extracts, Antistress I and Antistress II, decreased TNF-α and IL-6 levels, while Antistress I also reduced the levels of the anti-inflammatory cytokine IL-10. The combinations of plant extracts used in our experiment have not been previously studied or documented in the available literature. However, based on our own experimental results, we can draw the conclusion that the combinations exhibit a more pronounced effect in reducing cytokine levels compared to the individual plant extracts.

Polymer Tablet Matrix Systems for the Controlled Release of Dry Betula pendula Leaf Extract.

The aim of the study was to develop polymer matrix tablets with modified release of dry Betula pendula leaf extract and to investigate basic parameters influencing the drug release pattern. To fully assess the statistical significance of the influence of the individual factors in the tablet formulation development as well as the combination of them, Tukey's tests and a complete 33 factor analysis of variance (ANOVA) were applied. The following three factors were studied at three levels (low, medium and high): influence of the hydrophobic/hydrophilic polymer ratio Ethylcellulose (EC)/Hydroxypropyl methylcellulose (HPMC) (40/60, 25/75 and 10/90), influence of HPMC molecular weight (500 kDa, 750 kDa and 1150 kDa), and influence of the compression force applied (1 t, 1.5 t and 2 t). The effect of these varied parameters on the drug release parameter t80 was evaluated statistically. Twenty-seven tablet models were formulated, including all possible combinations of the variables. The obtained drug release profiles demonstrated that a 25/75 (EC/HPMC) ratio was the most suitable for prolonging the release process. Increasing the molecular weight of HMPC from 500 kDa to 750-1150 kDa and applying higher compression force significantly influenced the studied t80 values and caused sustained drug release (t80 up to 7.97 h). The combination of the hydrophilic HPMC polymer with the hydrophobic EC can result in the formation of a promising drug-carrying matrix, offering effective control of the drug release process.

Composition and chronic toxicity of dry methanol-aqueous extract of wild-growing Satureja montana.

INTRODUCTION: Saturejamontana is a wild growing medicinal plant, part of the Lamiaceae family. This herb is well known as a source of phenolic compounds, which can vary in a broad range depending on different factors and exert many pharmacological activities.

A study of flavonoid composition and antimicrobial activity of Scutellaria altissima L. from different floristic regions of Bulgaria.

INTRODUCTION: Scutellaria extracts and its constituents, especially the characteristic flavonoids such as baicalein and its glycoside baicalin, exhibit significant antimicrobial activity. AIM: To perform a comparative analysis of flavonoid composition and antimicrobial activity of extracts obtained from aerial parts and roots of Scutellaria altissima from the regions of Mezek and Bachkovo, Bulgaria. MATERIALS AND METHODS: 70% ethanol and aqueous extracts of aerial parts and roots of S. altissima were used. HPLC analysis of S. altissima extracts was performed. Microbiological tests were done on clinical isolates of Streptococcus mitis, Staphylococcus aureus, Escherichia coli, and Candida albicans. Minimal bactericidal and minimal bacteriostatic concentrations of S. altissima extracts were determined by the agar method. RESULTS: The ethanol extracts contain flavonoids approximately twice as much in comparison with the aqueous extracts. The baicalin content in the aerial parts of S. altissima from the region of Mezek is 5 times higher than that in the roots. S. altissima extracts have effective antimicrobial activity against S. mitis only. The minimal bactericidal concentration of ethanol extracts of S. altissima aerial parts and S. altissima roots is 2000 µg/ml and 8000 µg/ml at 24 hours, respectively. The bactericidal effect of aqueous extracts occurs at 48 hours at minimal bactericidal concentration of S. altissima aerial parts - 2000 µg/ml and of S. altissima roots - 6000 µg/ml. CONCLUSIONS: The finding that extracts of Bulgarian S. altissima possess effective antimicrobial properties against S. mitis suggests that it can be used as a potential source for the development of natural antimicrobial agents to suppress oral pathogens and prevent some oral infections.

Efficacy of Inotuzumab Ozogamicin plus Ponatinib Followed by Allogeneic Stem Cell Transplantation in a Patient with Relapsed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia.

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) is an aggressive disease with poor outcomes. Despite the incorporation of tyrosine kinase inhibitors (TKIs) in the therapeutic strategies, patients who relapse after chemotherapy plus TKI have poor overall survival (OS) and less chance to proceed to hematopoietic stem cell transplantation (HSCT) which remains the only curative approach. Therefore, new drugs, such as antibody-targeted therapies alone or in combination with TKIs, offer new therapeutic options for those patients. However, the combination of inotuzumab plus ponatinib has limited application. We present a case of a patient affected by Ph + ALL with T315I mutation successfully treated after early relapse with inotuzumab plus ponatinib, followed by allogeneic HSCT and ponatinib maintenance.

Phytochemical Composition, Antioxidant and Antimicrobial Activity of the Balkan Endemic Micromeria frivaldszkyana (Degen) Velen. (Lamiaceae).

The current study investigates the content of sugars, organic acids, phenolic acids and flavonoids, as well as antioxidant and antimicrobial activity of Balkan-endemic Micromeria frivaldszkyana. Glucose was the most abundant sugar in the plant (2.77%), followed by fructose (1.18%) and galactose (0.82%). Eight organic acids were detected with quinic acid being in the highest content-556.3 mg/100 g DW. From the individual phenolic acids, rosmarinic acid was found in the most significant amounts (2040.1 ± 1.97 mg/100 g) and hesperidin was the major representative of flavonoids with content 131.2 ± 5.6 mg/100 g DW. The antioxidant activity of the plant was studied by six methods: 2,2'-diphenylpicrylhydrazyl (DPPH)-286.4 ± 10.43 mM TE/g, 2,2'azinobis (3)-ethylbenzthiazoline-6-sulfonic acid (ABTS)-358.4 ± 10.4 mM TE/g, ferric reducing antioxidant power (FRAP)-388.0 ± 32.4 mM TE/g, cupric reducing antioxidant capacity (CUPRAC)-905.6 ± 19.2 mM TE/g, Oxygen Radical Absorbance Capacity (ORAC)-3250.5 ± 208.1 µmol TE/g and Hydroxyl Radical Averting Capacity (HORAC)-306.1 ± 23.5 µmol GAE/g. In vitro antimicrobial activity against nine microorganism was evaluated but the extract displayed antimicrobial activity only against Listeria monocytogenes ATCC 19111 with inhibition zone diameter 9 mm and minimal inhibitory concentration (MIC) 10 mg/mL.

Metabolite Profile and Antioxidant Activity of Some Species of Genus Scutellaria Growing in Bulgaria.

Until now, the interest to plants from genus Scutellaria in Bulgaria has been focused mainly on the terpenes in them. The purpose of this study is to enrich the information on the composition of the Bulgarian Scutellaria species in terms of both polyphenolic content as well as primary metabolites such as mono-, oligosaccharides and organic acids. An aerial part of three Scutellaria species growing in four low mountain regions of Southern Bulgaria was used. The flavonoids scutellarin, baicalin, baicalein, wogonin, wogonoside, luteolin, chrysin and a caffeoyl phenylethanoid glycoside-verbascoside have been identified via HPLC in different extracts from Scutellaria altissima, Scutellaria albida and Scutellaria galericulata. The antioxidant activity of the extracts has been evaluated. The Scutellaria altissima from Mezek and Scutellaria galericulata from Parvenets we studied, which are the richest in flavonoids (represented mainly by baicalin, scutellarin and wogonoside), show the highest Oxygen Radical Absorption Capacity. Hydroxyl Radical Averting Capacity of Scutellaria albida from Mezek and Scutellaria altissima from Bachkovo is the most pronounced, probably due to the content of scutellarin and luteolin and chrysin, respectively. Antioxidant activity of aqueous, methanolic and 70% and 96% ethanol extracts were also determined by the electrochemical method.

Aronia melanocarpa (Michx.) Elliot fruit juice reveals neuroprotective effect and improves cognitive and locomotor functions of aged rats.

The aim of the study was to investigate the effect of polyphenol-rich Aronia melanocarpa (Michx.) Elliot juice (AMJ) on learning ability and memory, and brain morphology of aged rats. A model of healthy male Wistar rats (24 months of age) divided in 2 groups was used: AMJ group supplemented orally with AMJ (10 mL/kg for 105 days) and old control (CO) group without supplementation. Activity cage test showed that AMJ supplemented rats increased the number of vertical movements compared with old controls (p < 0.05). In active avoidance test, supplemented rats increased the number of avoidances on 3rd, 4th and 5th days of learning session, compared with the respective day of old controls (p < 0.05). AMJ supplementation did not affect the mean neuronal number in the dentate gyrus but significantly increased the density of nerve fibers in the perforant path of the hippocampus (p < 0.05). AMJ supplementation increased acetylcholinesterase activity in hippocampus, which is a marker of improved functional activity of the cholinergic neurons. These results indicate that AMJ induced ameliorating changes in the ability of old rats to learn tasks and improved their locomotor functions. AMJ showed a neuroprotective effect by increasing the density of nerve fibers in the hippocampal perforant pathway.

Antidepressant Effect and Recognition Memory Improvement of Two Novel Plant Extract Combinations - Antistress I and Anti-stress II on Rats Subjected to a Model of Mild Chronic Stress.

BACKGROUND: Chronic stress is one of the main factors which lead to depression - a psychiatric disorder affecting millions of people and predicted to be the second ranked cause of premature death in 2020. Depression is often associated with cognitive disturbances and memory deficit. Plant based therapy could be effective in the treatment of mild to moderate depression due to its low level of adverse reaction, its good tolerability and compliance. MATERIALS AND METHODS: 72 male Wistar rats, divided in 9 groups were given orally for 8 weeks two combinations of dry plant extracts - Antistress I and Antistress II and five individual dry extracts obtained from Serratula coronata, Hypericum perforatum, Valeriana officinalis, Crataegus monogyna and Melissa officinalis. The animals were exposed to a chronic unpredictable mild stress for 8 weeks. The depression-like symptoms were evaluated with Forced swim test while the assessment of the memory deficit was performed with Novel object recognition test. RESULTS: Antistress II demonstrates antidepressant effect while Antistress I doesn't improve the depressive-like symptoms. The individual extracts of Hypericum perforatum and Valeriana officinalis also possess antidepressant properties. Antistress II improves the cognition as well as the individual extracts of Hypericum perforatum, Valeriana officinalis and especially Serratula coronata. Dry extract from Serratula tend to have the best effect regarding the recognition memory. The effect of Antistress I on memory deficit is negligible. CONCLUSIONS: Antistress II possesses antidepressant effect and improves the recognition memory while Antistress I doesn't demonstrate any of the above-described effects.

Ketoprofen-loaded polymer carriers in bigel formulation: an approach to enhancing drug photostability in topical application forms.

The purpose of the study was to investigate the stability and biopharmaceutical characteristics of ketoprofen, loaded in polymeric carriers, which were included into a bigel in a semisolid dosage form. The polymer carriers with in situ-included ketoprofen were obtained by emulsifier-free emulsion polymerization of the monomers in aqueous medium or a solution of the polymers used. The morphological characteristics of the carriers, the in vitro release and the photochemical stability of ketoprofen were evaluated. The model with optimal characteristics was included in a bigel formulation. The bigel was characterized in terms of pH, rheological behavior, spreadability, and in vitro drug release. Acute skin toxicity, antinociceptive activity, anti-inflammatory activity, and antihyperalgesic effects of the prepared bigel with ketoprofen-loaded polymer carrier were evaluated. The carriers of ketoprofen were characterized by a high yield and drug loading. The particle size distribution varied widely according to the polymer used, and a sustained release was provided for up to 6 hours. The polymer mixture poly(vinyl acetate) and hydroxypropyl cellulose as a drug carrier, alone or included in the bigel composition, improved the photostability of the drug compared with unprotected ketoprofen. The bigel with ketoprofen-loaded particles provided sustained release of the drug and had optimal rheological parameters. In vivo experiments on the bigel showed no skin inflammation or irritation. Four hours after its application, a well-defined analgesic, anti-inflammatory, and antihyperalgesic effect was registered. The polymer mixture of poly(vinyl acetate) and hydroxypropyl cellulose as a carrier of ketoprofen and the bigel in which it was included provided an enhanced photostability and sustained drug release.

Production of metabolites with antioxidant and emulsifying properties by antarctic strain Sporobolomyces salmonicolor AL1.

The Sporobolomyces salmonicolor AL(1) Antarctic strain was cultivated and two bioproducts were obtained: exopolysaccharide and biomass. The biologically active substances ergosterol, torularhodin, torulene, ß-carotene and CoQ(10) were extracted from the biomass and were quantified as follows: ergosterol 5.2 ± 0.2 mg/g, torularhodin 458.3 ± 24.5 µg/g, torulene 273.7 ± 14.5 µg/g, ß-carotene 129.2 ± 7.3 µg/g and coenzyme Q(10) (CoQ(10)) 236.1 ± 12.1 µg/g. Their antioxidant activity was estimated according to the cathode voltammetry method. The most pronounced antioxidant activity (according to trolox) was exhibited by ß-carotene 3.78, followed by CoQ(10) 3.60, both of them being the main contributors to the total extract activity of 3.19. The biologically active metabolites in combination with exoglucomannan as emulsifier were used for the creation of model emulsion systems characterised by great stability. The absorption of UVA rays by the model emulsions was studied.

Synthesis and characterization of an exopolysaccharide by antarctic yeast strain Cryptococcus laurentii AL100.

An exopolysaccharide-producing Antarctic yeast strain was selected and identified as Cryptococcus laurentii AL100. The physiological properties of the strain and its ability to utilize and biotransform different carbon sources (pentoses, hexoses, and oligosaccharides) into exopolysaccharide and biomass were investigated. Sucrose was chosen as a suitable and accessible carbon source. The biosynthetic capacity of the strain was studied in its dynamics at different sucrose concentrations (20, 30, 40, and 50 g/L) and temperatures (22 and 24 °C). The maximum biopolymer quantity of 6.4 g/L was obtained at 40 g/L of sucrose, 22 °C temperature and 96-h fermentation duration. The newly synthesized microbial carbohydrate was a heteropolysaccharide having the following monosaccharide composition: arabinose, 61.1%; mannose, 15.0%; glucose, 12.0%; galactose, 5.9%; and rhamnose, 2.8%. It was characterized by polydispersity of the polymer molecule, 60% of it having molecular mass of 4200 Da. The exopolysaccharide demonstrated good emulsifying and stabilizing properties with regard to oil/water emulsions and a pronounced synergistic effect with other hydrocolloids such as xanthan gum, guar gum, and alginate.

Synthesis of coenzyme Q10 and beta-carotene by yeasts isolated from antarctic soil and lichen in response to ultraviolet and visible radiations.

The effect of different doses of visible (Vis), ultraviolet-capital A, Cyrillic (UVA), and mixed light (UVA + Vis) upon coenzyme Q(10) (CoQ(10)) and beta-carotene synthesis and biomass yield by the Sporobolomyces salmonicolor AL(1), Cryptococcus albidus AS(55), Cryptococcus laurentii AS(56), and C. laurentii AS(58) strains isolated from Antarctic samples was investigated. The beta-carotene concentration in the red strain biomass increased by 52% under irradiation with 11 J/cm(2) Vis, and the CoQ(10) concentration rose by 37% in relation to the control quantity obtained through dark cultivation. Under irradiation with 6 J/cm(2) UVA, the S. salmonicolor AL(1) strain synthesized 15% more beta-carotene; C. albidus AS(55), 22%; C. laurentii AS(56), 44%; and C. laurentii AS(58), 35% in relation to the control quantity. Irradiation with a low UVcapital A, Cyrillic + Vis dose significantly stimulated beta-carotene biosynthesis by the strains of the Cryptococcus genus (87%, 138%, and 100%), whereas S. salmonicolor AL(1) increased the beta-carotene content to a smaller degree (55%). Higher doses of all three irradiation types inhibited beta-carotene accumulation. Vis suppressed CoQ(10) biosynthesis in the Cryptococcus strains, whereas UVcapital A, Cyrillic and UVcapital A, Cyrillic + Vis inhibited it in all four strains. The S. salmonicolor AL(1) strain pre-treated with 0.02 J/cm(2) UVA synthesized twice as much CoQ(10) and beta-carotene when cultivated in the presence of Vis light in an 11-J/cm(2) dose.

A study of chemical composition and antimicrobial activity of Bulgarian propolis.

UNLABELLED: Propolis is a natural product which exhibits pronounced antimicrobial and anti-inflammatory effects. AIM: To analyze the chemical composition and antimicrobial effect of Bulgarian propolis, p-cumaric acid and ferulic acid on certain Gram-positive and Gram-negative microorganisms. MATERIAL AND METHODS: Ethanol extract of Bulgarian propolis (Propolin) and water extract of Bulgarian propolis (Propolstom), ferulic acid and p-cumaric acid were used. The chemical HPLC-analysis of propolis was performed with Varian Prostar system. Microbiological tests were done on isolates of Streptococcus beta-haemolyticus, Enterococcus faecalis, Candida albicans and Escherichia coli. Non-treated and ethanol-treated cultures of the corresponding strains were used as controls. Minimal bactericidal and bacteriostatic concentration of Propolin were determined by agar method. RESULTS: The concentration of p-cumaric acid and ferulic acid in ethanol extract of propolis is about 1%. The minimal bactericidal concentration of Bulgarian propolis against Streptococcus beta-haemolyticus is 281 +/- 89.3 microg/ml, against Enterococcus faecalis--3490 +/- 633.1 microg/ml, against Candida albicans--1375 +/- 255.2 microg/ml, and against Escherichia coli--24306 +/- 1706.4 microg/ml. The minimal bactericidal concentration of p-cumaric acid and ferulic acid against Streptococcus beta-haemolyticus is 212 +/- 6.5 microg/ml and 208 +/- 7.7 microg/ml, against Enterococcus faecalis--3013 +/- 176.6 and 3032 +/- 203.4 microg/ml, against Candida albicans--157 +/- 15.5 microg/ml and 149 +/- 23.2 microg/ml, and against Escherichia coli--798 +/- 7.7 microg/ml and 801 +/- 22.8 microg/ml, respectively. CONCLUSIONS: The phenolic compounds p-cumaric acid and ferulic acid are 10 times less extracted in water extraction than in ethanol extraction. The most susceptible strains to the Bulgarian propolis and phenolic compounds are Streptococcus beta-haemolyticus and Candida albicans and the least affected are Escherichia coli and Enterococcus faecalis.