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Detalles de la revista
Formato
Revista
eISSN
1846-9558
Publicado por primera vez
28 Feb 2007
Periodo de publicación
4 veces al año
Idiomas
Inglés

Buscar

Volumen 69 (2019): Edición 4 (December 2019)

Detalles de la revista
Formato
Revista
eISSN
1846-9558
Publicado por primera vez
28 Feb 2007
Periodo de publicación
4 veces al año
Idiomas
Inglés

Buscar

17 Artículos
Acceso abierto

Anticancer effects of olive oil polyphenols and their combinations with anticancer drugs

Publicado en línea: 21 Oct 2019
Páginas: 461 - 482

Resumen

Abstract

Cancer presents one of the leading causes of death in the world. Current treatment includes the administration of one or more anticancer drugs, commonly known as chemotherapy. The biggest issue concerning the chemotherapeutics is their toxicity on normal cells and persisting side effects. One approach to the issue is chemoprevention and the other one is the discovery of more effective drugs or drug combinations, including combinations with polyphenols. Olive oil polyphenols (OOPs), especially hydroxytyrosol (HTyr), tyrosol (Tyr) and their derivatives oleuropein (Ole), oleacein and oleocanthal (Oc) express anticancer activity on different cancer models. Recent studies report that phenolic extract of virgin olive oil may be more effective than the individual phenolic compounds. Also, there is a growing body of evidence about the combined treatment of OOPs with various anticancer drugs, such as cisplatin, tamoxifen, doxorubicin and others. These novel approaches may present an advanced strategy in the prevention and treatment of cancer.

Palabras clave

  • olive polyphenols
  • anticancer
  • chemoprotective
  • synergism
Acceso abierto

Antithrombotic activity of flavonoids and polyphenols rich plant species

Publicado en línea: 21 Oct 2019
Páginas: 483 - 495

Resumen

Abstract

Cardiovascular diseases represent one of the most notable health problems of the modern civilization. Stroke and heart attack often lead to lethal outcome; essential problem underneath being thrombus formation. Prophylactic approaches include acetylsalicylic acid and clopidogrel therapy on the level of primary hemostasis, i.e., primary clot formation. In the last five years, in the USA, health care expenses related to cardiovascular diseases have increased 50 %, to over 350 billion dollars. Thus, application of plant species and medicinal plants rich in polyphenols in prevention of thrombus formation are of interest. This is supported by the fact that the number of publications on antiaggregatory effect of polyphenols has doubled in the last decade. In this review we focus on antiaggregatory effect of most abundant polyphenols – flavonoids, the effect of plant extracts rich in polyphenols (propolis, species Salvia sp., Calamintha nepeta L., Lavandula angustifolia Mill., Melissa officinalis L, Mentha x piperita L., Ocimum basilicum L., Origanum vulgare L., Rosmarinus officinalis L.) on platelet aggregation, association of chemical composition and antioxidant properties with the observed biological effect, and possible clinical significance of the published results.

Palabras clave

  • platelet aggregation
  • polyphenols
  • plant species
  • cardiovascular diseases
Acceso abierto

Nutrition – facts and myths

Publicado en línea: 21 Oct 2019
Páginas: 497 - 510

Resumen

Abstract

Taking responsibility for your life, among other factors, means also considering what to eat and which nutrition pattern to follow. Everyone needs to think about what they put on the plate and which ingredients should be avoided. Food, as such, will never be a drug or medication, like a painkilling tablet relieving pain in a short amount of time, for example. However, proper nutrition is our ally in the prevention of diseases, maintaining balance in our body and our mind. By following the main principles of a healthy diet, the physiological homeostasis can be managed, as well as faster recovery from disease achieved.

This review is aimed at summarizing basic principles of nutrition recommendations and at empowering stakeholders (pharmacists, medical biochemists, physicians) to be able to communicate to their patients and customers healthy and sustainable nutrition choices through the personalized advice.

Palabras clave

  • nutrition
  • personalized approach
  • biologically active substances
  • Mediterranean diet
  • liquid biopsy
  • microbiota
Acceso abierto

A modern approach to the treatment of plaque psoriasis

Publicado en línea: 21 Oct 2019
Páginas: 511 - 523

Resumen

Abstract

Psoriasis is a common chronic inflammatory skin disease which affects 0.5–1 % of children and 2–3 % of the adult population. In Croatia, 1.6 % of the population suffer from psoriasis. Distribution of the disease is bimodal, with the first peak at the age of 20–30, and the second at the age of 50–60. The etiopathogenesis of the disease is multifactorial, the key factors being genetic predisposition combined with immunological disorders, environmental factors and skin barrier damage. There are several clinical variants of the disease. The main signalling pathways in psoriasis include TNF-α, IL-23 and IL-17. Topical agents are used for the treatment of the mild form, and the systemic conventional therapy is used for the treatment of moderate to severe forms of the disease. In cases where’s no response, or intolerance or contraindications are present, new targeted medications are to be administered. Development in the field of immunogenetics of psoriasis leads to personalized medicine.

Palabras clave

  • psoriasis
  • topical treatment
  • conventional systemic therapy
  • small molecules
  • biologicals
Acceso abierto

Application of medicinal plants in several dermatovenerological entities

Publicado en línea: 21 Oct 2019
Páginas: 525 - 531

Resumen

Abstract

Treatment of skin conditions with medicinal plants has been an ongoing human activity lasting over thousands of years. The use of specific plant species developed regionally, based on local flora. Commonly used medicinal plants for dermatological complaints are: Phlebodium aureum (L.) J. Sm., Ginkgo biloba L., Rosmarinus officinalis L., Panax ginseng C.A.Mey., Allium cepa L., Aloe vera (L.) Burm.f., Capsicum annuum L., Berbe ris aquifolium Pursh, Camellia sinensis (L.) Kuntze, and Podophyllum peltatum L.

The demand for complementary therapeutics is an emerging trend due to the awareness of potential side effects that synthetic drugs might cause. More scientific evidence and better documentation are needed before advising dermatologic patients on herbal medicinal treatment. Standardised extracts and formulations with proven clinical efficacy should be developed for this cause. Here provided review entails the use of herbal medicinal products in the treatment of frequent chronic skin diseases, such as vitiligo, alopecia, psoriasis and genital warts.

Palabras clave

  • medicinal plants
  • vitiligo
  • alopecia
  • psoriasis
  • genital warts
Acceso abierto

Actualities in the phytochemical research on selected terpenes

Publicado en línea: 21 Oct 2019
Páginas: 533 - 540

Resumen

Abstract

A short review of our recent research on the essential oil phytochemical composition of Petasites albus (L.) Gaertn. and Petasites hybridus (L.) G. Gaertn., B. Mey. & Scherb. (Asteraceae) as well as on the oils of Globularia cordifolia L., Globularia meridionalis (Podp.) O. Schwarz and Globularia punctata Lapeyr. (Plantaginaceae) is presented. All essential oils contained a variety of oxygenated sesquiterpenes among their major constituents, including a bakkane type sesquiterpene fukinanolid (bakkenolide A). The paper is focused on: i) a short overview of the abundance of major terpenes in the essential oils of Petasites and Globularia species from Croatia; ii) possible biosynthetic pathways of major identified sesquiterpenes; and iii) biological activities (literature data) of major sesquiterpenes from Petasites and Globularia species.

Palabras clave

  • species
  • species
  • oxygenated sesquiterpenes
  • bisabola-2
  • 10-diene-1-one
  • fukinanolid (bakkenolide A)
  • dehydrofukinone
Acceso abierto

Screening of flavonoid aglycons’ metabolism mediated by the human liver cytochromes P450

Publicado en línea: 21 Oct 2019
Páginas: 541 - 562

Resumen

Abstract

Biological effects of flavonoids have been extensively studied in the last 80 years. As flavonoids represent a rather large group of compounds, data on metabolic biotransformations of these compounds is relatively limited to those well studied. The objective of this study was to screen the metabolism of 30 selected flavonoid aglycons mediated by the most relevant metabolic enzymes, human liver cytochromes P450. For this purpose, in vitro experiments with human liver microsomes and recombinant enzymes were conducted. To evaluate flavonoid’s metabolism and structure of the products, high-performance liquid chromatography coupled with high-resolution mass spectrometry was used. Out of 30 flavonoids, 15 were susceptible to oxidative metabolism mediated by cytochromes P450. Dominant reactions were aromatic hydroxylation and O-demethylation, or a combination of these reactions. The dominant enzyme responsible for the observed metabolic reactions is CYP1A2, whereas other human liver cytochromes P450, namely, CYP2C19, CYP2D6, CYP2E1 and CYP3A4, contribute to flavonoid metabolism to a lesser degree. These results, to some extent, contribute to the understanding of the metabolism of constituents found in antioxidant dietary supplements and their possible interactions with other xenobiotics, i.e., medicinal products.

Palabras clave

  • flavonoids
  • human liver cytochromes P450
  • metabolism
  • HPLC
  • MS
Acceso abierto

Evaluation of phenylethylamine type entactogens and their metabolites relevant to ecotoxicology – a QSAR study

Publicado en línea: 21 Oct 2019
Páginas: 563 - 584

Resumen

Abstract

The impact of the selected entactogens and their o-quinone metabolites on the environment was explored in QSAR studies by the use of predicted molecular descriptors, ADMET properties and environmental toxicity parameters, i.e., acute toxicity in Tetrahymena pyriformis (TOX_ATTP) expressed as Th_pyr_pIGC50/mmol L−1, acute toxicity in Pimephales promelas, the fathead minnow (TOX_FHM) expressed as Minnow LC50/mg L−1, the acute toxicity in Daphnia magna (TOX_DM) expressed as Daphnia LC50/mg L−1 and bioconcentration factor (BCF).

The formation of corresponding o-quinones via benzo-dioxo-lone ring, O-demethylenation was predicted as the main metabolic pathway for all entactogens except for 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)propan-2-amine (DiFMDA). The least favourable ADMET profile was revealed for N-(1-(benzo[d][1,3]dioxol-5-yl)propan-2-yl)-O-methylhydroxylamine (MDMEO).

QSAR studies revealed significant linear correlations between MlogP of entactogens and MlogP of o-quinone metabolites (R = 0.99), and Th_pyr_pIGC50/mmol L−1 (R = 0.94), also their MlogPs with Minnow_LC50/mg L−1 (R = 0.80 and R = 0.78), BCF (R = 0.86 and R = 0.82) and percentage of o-quinones’ yields (R = 0.73 and R = 0.80). Entactogens were predicted as non-biodegradable molecules, whereas the majority of their o-quinones were biodegradable.

Palabras clave

  • entactogens
  • ecstasy
  • ADMET
  • CYP metabolism
  • ecotoxicity
  • QSAR
Acceso abierto

Implementation of medication management services at the primary healthcare level – a pilot study

Publicado en línea: 21 Oct 2019
Páginas: 585 - 606

Resumen

Abstract

This study employed a mixed-method approach to enable the implementation of comprehensive medication management (CMM) services in Croatia’s primary care setting. Drug therapy problems (DTPs) and factors associated with their occurrence were determined in patients with chronic diseases from January 2018 to April 2019. The pre-implementation stage established the foundations for the early implementation stage, in which the practice was set up, the patients’ recruitment initiated and various challenges identified. During the study period, 86 patients were recruited for CMM provision. Overall, 2.8 DTPs (± 1.6) per patient were identified and the majority (96.2 %) presented with at least one DTP. Multiple regression analysis showed that type 2 diabetic patients (p = 0.025) and patients using five or more medications (p = 0.011) should be prioritized to receive CMM services as potentially they have a higher number of DTPs, and could, therefore, obtain a greater benefit from the service.

Palabras clave

  • comprehensive medication management services
  • drug therapy problems
  • risk factors
  • pharmaceutical care
  • primary care
  • implementation stage
Acceso abierto

Influence of flavonoids’ lipophilicity on platelet aggregation

Publicado en línea: 21 Oct 2019
Páginas: 607 - 619

Resumen

Abstract

Flavonoids are natural polyphenolic compounds present in a wide spectrum of plants that have a beneficial effect on human health. In the context of cardiovascular diseases related to plaque and thrombus formation, flavonoids exhibit an anti-aggregatory effect. Previously, it has been reported that all tested flavonoids exhibit an antiaggregatory effect on platelet aggregation when measured by impedance aggregometry on whole blood, in the test of aggregation induced by adenosine diphosphate (ADP). As not all flavonoids have the same targets within signaling pathways, an assumption of a common non-specific mechanism related to lipophilicity is to be considered. To test this hypothesis, reverse-phase thin layer chromatography was used to assess the lipophilicity of flavonoids; impedance aggregometry was used for testing of platelet aggregation and flow cytometry to monitor the influence of flavonoids on platelet activation. Lipophilicity analysis showed a highly negative correlation of logP and MINaAC for groups of flavones and flavanones. As determined by flow cytometry, the exposition of receptors necessary for the promotion of platelet activation and primary clot formation was diminished, i.e., lowered expression of the activated form of integrin αIIbβ3 was observed in the presence of flavanone. Platelet membrane stabilization by flavonoids as a mechanism of antiaggregatory effect has been supported by impedance aggregometry experiments when specific inhibitors of platelet aggregation signaling pathways (U73122, indomethacin, verapamil) were used in the presence of a weak (ADP) and a strong (TRAP-6) agonist of aggregation. While individual flavonoids can have specific targets within aggregation signaling pathways, all flavonoids share a common non-specific mechanism of platelet aggregation inhibition related to their lipophilicity and membrane stabilization that, to some extent, contributes to their antiaggregatory effect.

Palabras clave

  • flavonoids
  • platelets
  • lipophilicity
  • flow cyto metry
  • antiaggregatory activity
Acceso abierto

In vitro evaluation of stearylamine cationic nanoemulsions for improved ocular drug delivery

Publicado en línea: 21 Oct 2019
Páginas: 621 - 634

Resumen

Abstract

Oil-in-water nanoemulsions (NEs) represent one of the formulation approaches to improve eye-related bio-availability of lipophilic drugs. The potential of cationic NEs is pronounced due to the electrostatic interaction of positively charged droplets with negatively charged mucins present in the tear film, providing prolonged formulation residence at the ocular surface. The aim of this study was to develop a cationic ophthalmic NE with cationic lipid stearylamine (SA) as a carrier of a positive charge. The addition of a nonionic surfactant provided the dual electro-steric stabilization of NEs and enabled tuning of SA concentration to achieve an optimal balance between its interaction with mucins and biocompatibility. Physicochemical characterization, stability profile, in vitro mucoadhesion study and biocompatibility study employing 3D HCE-T cell-based model of corneal epithelium pointed out the NE with 0.05 % (m/m) SA as the leading formulation. Minimizing SA content while retaining droplet/mucin interactions is of great importance for efficacy and safety of future ophthalmic drug products.

Palabras clave

  • cationic nanoemulsions
  • stearylamine
  • ophthalmic drug delivery
  • biocompatibility
  • mucoadhesion
Acceso abierto

Evaluation of stability and in vitro wound healing potential of melatonin loaded (lipid enriched) chitosan based microspheres

Publicado en línea: 21 Oct 2019
Páginas: 635 - 648

Resumen

Abstract

The aim of this study was to evaluate long-term stability and assess the wound healing potential of the innovative melatonin-loaded lipid-enriched hybrid system compared to conventional melatonin-loaded chitosan microspheres. The hybrid system contained nanostructured lipid carrier incorporated in the chitosan matrix, in order to modify melatonin release and alter physicochemical characteristics of the delivery system. Stability testing was performed during a six-month period under two conditions: refrigerated (5 ± 3 °C) and at room temperature (25 ± 2 °C/60 ± 5 % RH). Samples stored at both conditions were analyzed in terms of particle size, zeta potential, moisture content and thermal properties. At the end of testing, drug content was determined in all samples. Dressings wound healing potential was assessed by in vitro scratch test using human skin fibroblast cell line. Although both systems showed good stability characteristics, the addition of lipids in the system has improved its wound healing potential.

Palabras clave

  • melatonin
  • nanoparticles
  • microspheres
  • chitosan
  • stability
  • wound healing
Acceso abierto

Miniaturized shake-flask HPLC method for determination of distribution coefficient of drugs used in inflammatory bowel diseases

Publicado en línea: 21 Oct 2019
Páginas: 649 - 660

Resumen

Abstract

A new method for determination of distribution coefficient of drugs azathioprine, 6-mercaptopurine and 6-thioguanine and nutrient folic acid used in the treatment of inflammatory bowel disease based on a miniaturized shake-flask and HPLC/DAD was developed. Special attention was made to the most commonly reported problems in the measurement of distribution coefficients using a shake-flask method such as mixing technique, speed and time, the temperature of experiment, type of buffer and its pH as well as n-octanol/buffer phase ratio. The concentration of compounds in the buffer is determined by HPLC directly from shake flasks or conventional 2-mL vials. The developed method was fully validated according to ICH guidelines. Furthermore, experimental data were successfully compared with lipophilicity and human intestinal absorption calculated by the use of four different theoretical approaches. The method shows potential for high-throughput measurements of a large number of compounds.

Palabras clave

  • distribution coefficient logarithm
  • shake-flask
  • HPLC
  • inflammatory bowel disease
Acceso abierto

Antiproliferative evaluation of various aminoquinoline derivatives

Publicado en línea: 21 Oct 2019
Páginas: 661 - 672

Resumen

Abstract

Four classes of aminoquinoline derivatives were prepared: primaquine ureas 1af, primaquine bis-ureas 2af, chloroquine fumardiamides 3af and mefloquine fumardiamides 4af. Their antiproliferative activities against breast adeno-carcinoma (MCF-7), lung carcinoma (H460) and colon carcinoma (HCT 116 and SW620) cell lines were evaluated in vitro, using MTT cell proliferation assay. The results revealed a low activity of primaquine urea and bis-urea derivatives and high activity of all fumardiamides, with IC50 values in low micromolar range against all tested cancer cell lines.

Palabras clave

  • primaquine
  • chloroquine
  • mefloquine
  • fumardiamide
  • antiproliferative activity
Acceso abierto

Phenolic compounds of Iris adriatica and their antimycobacterial effects

Publicado en línea: 21 Oct 2019
Páginas: 673 - 681

Resumen

Abstract

Little is known about the pharmacological activities of Iris adriatica (Iridaceae), a plant endemic to Dalmatia (Croatia). We therefore performed a bioassay-guided fractionation including high-performance counter current chromatography (HPCCC) and antibacterial tests using Mycobacterium smegmatis mc2 155. One obtained fraction was found to be antimycobacterially active with a MIC of 64 mg L−1. Furthermore, fractions were tested for resistance modulatory effects using ethidium bromide as substrate. We were able to identify the pure isoflavonic compounds irigenin and irilone and a fraction containing mainly benzophenone 2,4,6-trihydroxy-4-methoxy-benzophenone, responsible for the resistance-modulatory activity of this plant.

Palabras clave

  • Radix Iridis
  • phenolic compounds
  • resistance modulation
  • ethidium bromide
  • MIC
Acceso abierto

Antiproliferative and genotoxic potential of xanthen-3-one derivatives

Publicado en línea: 21 Oct 2019
Páginas: 683 - 694

Resumen

Abstract

Twelve previously synthesized, biologically active 2,6,7-trihydroxyxanthen-3-one derivatives were evaluated in vitro for antiproliferative activity. Compounds were screened against HeLa, SW620, HepG2 and A549 tumor cell lines. Compound with the trifluormethyl group on C-4’ position of the phenyl ring showed the best inhibitory activity towards HeLa and A549 tumor cells with IC50 of 0.7 and 4.1 µmol L−1, resp. Compound with chlorine and fluorine substituents on aryl ring showed the best antiproliferative activity against SW620 with IC50 of 4.1 µmol L–1 and against HepG2 tumor cell line with IC50 of 4.2 µmol L–1. Analyses of cytotoxic and genotoxic potential of the trifluormethyl derivative were performed with cytokinesis-block micronucleus cytome assay in human lymphocyte culture and revealed no genotoxic and cytotoxic effects. The most potent compounds were subjected to molecular docking simulations in order to analyse bindings to molecular targets and, at the same time, further support the results of experimental cytotoxic tests. Docking studies showed sites of importance in forming hydrogen bonds of the most potent compounds with targets of interest.

Palabras clave

  • antiproliferative activity
  • genotoxic potential
  • docking study
  • xanthen-3-one derivatives
  • cytokinesis-block micronucleus cytome assay
Acceso abierto

Efficacy and safety of local lysozyme treatment in patients with oral mucositis after chemotherapy and radiotherapy

Publicado en línea: 21 Oct 2019
Páginas: 695 - 704

Resumen

Abstract

This observational clinical study was composed of two substudies: a non-comparative one (n = 166), testing only lysozyme-based compounds (LBCs), and a comparative substudy (n = 275), testing both LBCs and bicarbonate-based local compounds (BBCs) on the healing of oral mucositis during radio- or chemotherapy. The density of ulcerations has decreased significantly after the treatment with lysozyme in both substudies. The density of ulcerations in the radiotherapy group was lower in patients treated with LBCs compared to patients treated with BBCs (p < 0.001). In the chemotherapy group, reduction of ulceration density was similar with both LBCs and BBCs. The LBCs reduced pain intensity during the intake of solid food and speech more than BBCs in both patient cohorts (p < 0.05). In the radiotherapy cohort, pain intensity when consuming liquid foods was reduced more with LBCs than with BBCs (p < 0.05). No adverse events were recorded. This study demonstrates the advantages of treating oral mucositis during radiotherapy or chemo-therapy with LBCs.

Palabras clave

  • oral mucositis
  • treatment efficacy
  • radiotherapy
  • chemotherapy
  • topical
  • lysozyme
17 Artículos
Acceso abierto

Anticancer effects of olive oil polyphenols and their combinations with anticancer drugs

Publicado en línea: 21 Oct 2019
Páginas: 461 - 482

Resumen

Abstract

Cancer presents one of the leading causes of death in the world. Current treatment includes the administration of one or more anticancer drugs, commonly known as chemotherapy. The biggest issue concerning the chemotherapeutics is their toxicity on normal cells and persisting side effects. One approach to the issue is chemoprevention and the other one is the discovery of more effective drugs or drug combinations, including combinations with polyphenols. Olive oil polyphenols (OOPs), especially hydroxytyrosol (HTyr), tyrosol (Tyr) and their derivatives oleuropein (Ole), oleacein and oleocanthal (Oc) express anticancer activity on different cancer models. Recent studies report that phenolic extract of virgin olive oil may be more effective than the individual phenolic compounds. Also, there is a growing body of evidence about the combined treatment of OOPs with various anticancer drugs, such as cisplatin, tamoxifen, doxorubicin and others. These novel approaches may present an advanced strategy in the prevention and treatment of cancer.

Palabras clave

  • olive polyphenols
  • anticancer
  • chemoprotective
  • synergism
Acceso abierto

Antithrombotic activity of flavonoids and polyphenols rich plant species

Publicado en línea: 21 Oct 2019
Páginas: 483 - 495

Resumen

Abstract

Cardiovascular diseases represent one of the most notable health problems of the modern civilization. Stroke and heart attack often lead to lethal outcome; essential problem underneath being thrombus formation. Prophylactic approaches include acetylsalicylic acid and clopidogrel therapy on the level of primary hemostasis, i.e., primary clot formation. In the last five years, in the USA, health care expenses related to cardiovascular diseases have increased 50 %, to over 350 billion dollars. Thus, application of plant species and medicinal plants rich in polyphenols in prevention of thrombus formation are of interest. This is supported by the fact that the number of publications on antiaggregatory effect of polyphenols has doubled in the last decade. In this review we focus on antiaggregatory effect of most abundant polyphenols – flavonoids, the effect of plant extracts rich in polyphenols (propolis, species Salvia sp., Calamintha nepeta L., Lavandula angustifolia Mill., Melissa officinalis L, Mentha x piperita L., Ocimum basilicum L., Origanum vulgare L., Rosmarinus officinalis L.) on platelet aggregation, association of chemical composition and antioxidant properties with the observed biological effect, and possible clinical significance of the published results.

Palabras clave

  • platelet aggregation
  • polyphenols
  • plant species
  • cardiovascular diseases
Acceso abierto

Nutrition – facts and myths

Publicado en línea: 21 Oct 2019
Páginas: 497 - 510

Resumen

Abstract

Taking responsibility for your life, among other factors, means also considering what to eat and which nutrition pattern to follow. Everyone needs to think about what they put on the plate and which ingredients should be avoided. Food, as such, will never be a drug or medication, like a painkilling tablet relieving pain in a short amount of time, for example. However, proper nutrition is our ally in the prevention of diseases, maintaining balance in our body and our mind. By following the main principles of a healthy diet, the physiological homeostasis can be managed, as well as faster recovery from disease achieved.

This review is aimed at summarizing basic principles of nutrition recommendations and at empowering stakeholders (pharmacists, medical biochemists, physicians) to be able to communicate to their patients and customers healthy and sustainable nutrition choices through the personalized advice.

Palabras clave

  • nutrition
  • personalized approach
  • biologically active substances
  • Mediterranean diet
  • liquid biopsy
  • microbiota
Acceso abierto

A modern approach to the treatment of plaque psoriasis

Publicado en línea: 21 Oct 2019
Páginas: 511 - 523

Resumen

Abstract

Psoriasis is a common chronic inflammatory skin disease which affects 0.5–1 % of children and 2–3 % of the adult population. In Croatia, 1.6 % of the population suffer from psoriasis. Distribution of the disease is bimodal, with the first peak at the age of 20–30, and the second at the age of 50–60. The etiopathogenesis of the disease is multifactorial, the key factors being genetic predisposition combined with immunological disorders, environmental factors and skin barrier damage. There are several clinical variants of the disease. The main signalling pathways in psoriasis include TNF-α, IL-23 and IL-17. Topical agents are used for the treatment of the mild form, and the systemic conventional therapy is used for the treatment of moderate to severe forms of the disease. In cases where’s no response, or intolerance or contraindications are present, new targeted medications are to be administered. Development in the field of immunogenetics of psoriasis leads to personalized medicine.

Palabras clave

  • psoriasis
  • topical treatment
  • conventional systemic therapy
  • small molecules
  • biologicals
Acceso abierto

Application of medicinal plants in several dermatovenerological entities

Publicado en línea: 21 Oct 2019
Páginas: 525 - 531

Resumen

Abstract

Treatment of skin conditions with medicinal plants has been an ongoing human activity lasting over thousands of years. The use of specific plant species developed regionally, based on local flora. Commonly used medicinal plants for dermatological complaints are: Phlebodium aureum (L.) J. Sm., Ginkgo biloba L., Rosmarinus officinalis L., Panax ginseng C.A.Mey., Allium cepa L., Aloe vera (L.) Burm.f., Capsicum annuum L., Berbe ris aquifolium Pursh, Camellia sinensis (L.) Kuntze, and Podophyllum peltatum L.

The demand for complementary therapeutics is an emerging trend due to the awareness of potential side effects that synthetic drugs might cause. More scientific evidence and better documentation are needed before advising dermatologic patients on herbal medicinal treatment. Standardised extracts and formulations with proven clinical efficacy should be developed for this cause. Here provided review entails the use of herbal medicinal products in the treatment of frequent chronic skin diseases, such as vitiligo, alopecia, psoriasis and genital warts.

Palabras clave

  • medicinal plants
  • vitiligo
  • alopecia
  • psoriasis
  • genital warts
Acceso abierto

Actualities in the phytochemical research on selected terpenes

Publicado en línea: 21 Oct 2019
Páginas: 533 - 540

Resumen

Abstract

A short review of our recent research on the essential oil phytochemical composition of Petasites albus (L.) Gaertn. and Petasites hybridus (L.) G. Gaertn., B. Mey. & Scherb. (Asteraceae) as well as on the oils of Globularia cordifolia L., Globularia meridionalis (Podp.) O. Schwarz and Globularia punctata Lapeyr. (Plantaginaceae) is presented. All essential oils contained a variety of oxygenated sesquiterpenes among their major constituents, including a bakkane type sesquiterpene fukinanolid (bakkenolide A). The paper is focused on: i) a short overview of the abundance of major terpenes in the essential oils of Petasites and Globularia species from Croatia; ii) possible biosynthetic pathways of major identified sesquiterpenes; and iii) biological activities (literature data) of major sesquiterpenes from Petasites and Globularia species.

Palabras clave

  • species
  • species
  • oxygenated sesquiterpenes
  • bisabola-2
  • 10-diene-1-one
  • fukinanolid (bakkenolide A)
  • dehydrofukinone
Acceso abierto

Screening of flavonoid aglycons’ metabolism mediated by the human liver cytochromes P450

Publicado en línea: 21 Oct 2019
Páginas: 541 - 562

Resumen

Abstract

Biological effects of flavonoids have been extensively studied in the last 80 years. As flavonoids represent a rather large group of compounds, data on metabolic biotransformations of these compounds is relatively limited to those well studied. The objective of this study was to screen the metabolism of 30 selected flavonoid aglycons mediated by the most relevant metabolic enzymes, human liver cytochromes P450. For this purpose, in vitro experiments with human liver microsomes and recombinant enzymes were conducted. To evaluate flavonoid’s metabolism and structure of the products, high-performance liquid chromatography coupled with high-resolution mass spectrometry was used. Out of 30 flavonoids, 15 were susceptible to oxidative metabolism mediated by cytochromes P450. Dominant reactions were aromatic hydroxylation and O-demethylation, or a combination of these reactions. The dominant enzyme responsible for the observed metabolic reactions is CYP1A2, whereas other human liver cytochromes P450, namely, CYP2C19, CYP2D6, CYP2E1 and CYP3A4, contribute to flavonoid metabolism to a lesser degree. These results, to some extent, contribute to the understanding of the metabolism of constituents found in antioxidant dietary supplements and their possible interactions with other xenobiotics, i.e., medicinal products.

Palabras clave

  • flavonoids
  • human liver cytochromes P450
  • metabolism
  • HPLC
  • MS
Acceso abierto

Evaluation of phenylethylamine type entactogens and their metabolites relevant to ecotoxicology – a QSAR study

Publicado en línea: 21 Oct 2019
Páginas: 563 - 584

Resumen

Abstract

The impact of the selected entactogens and their o-quinone metabolites on the environment was explored in QSAR studies by the use of predicted molecular descriptors, ADMET properties and environmental toxicity parameters, i.e., acute toxicity in Tetrahymena pyriformis (TOX_ATTP) expressed as Th_pyr_pIGC50/mmol L−1, acute toxicity in Pimephales promelas, the fathead minnow (TOX_FHM) expressed as Minnow LC50/mg L−1, the acute toxicity in Daphnia magna (TOX_DM) expressed as Daphnia LC50/mg L−1 and bioconcentration factor (BCF).

The formation of corresponding o-quinones via benzo-dioxo-lone ring, O-demethylenation was predicted as the main metabolic pathway for all entactogens except for 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)propan-2-amine (DiFMDA). The least favourable ADMET profile was revealed for N-(1-(benzo[d][1,3]dioxol-5-yl)propan-2-yl)-O-methylhydroxylamine (MDMEO).

QSAR studies revealed significant linear correlations between MlogP of entactogens and MlogP of o-quinone metabolites (R = 0.99), and Th_pyr_pIGC50/mmol L−1 (R = 0.94), also their MlogPs with Minnow_LC50/mg L−1 (R = 0.80 and R = 0.78), BCF (R = 0.86 and R = 0.82) and percentage of o-quinones’ yields (R = 0.73 and R = 0.80). Entactogens were predicted as non-biodegradable molecules, whereas the majority of their o-quinones were biodegradable.

Palabras clave

  • entactogens
  • ecstasy
  • ADMET
  • CYP metabolism
  • ecotoxicity
  • QSAR
Acceso abierto

Implementation of medication management services at the primary healthcare level – a pilot study

Publicado en línea: 21 Oct 2019
Páginas: 585 - 606

Resumen

Abstract

This study employed a mixed-method approach to enable the implementation of comprehensive medication management (CMM) services in Croatia’s primary care setting. Drug therapy problems (DTPs) and factors associated with their occurrence were determined in patients with chronic diseases from January 2018 to April 2019. The pre-implementation stage established the foundations for the early implementation stage, in which the practice was set up, the patients’ recruitment initiated and various challenges identified. During the study period, 86 patients were recruited for CMM provision. Overall, 2.8 DTPs (± 1.6) per patient were identified and the majority (96.2 %) presented with at least one DTP. Multiple regression analysis showed that type 2 diabetic patients (p = 0.025) and patients using five or more medications (p = 0.011) should be prioritized to receive CMM services as potentially they have a higher number of DTPs, and could, therefore, obtain a greater benefit from the service.

Palabras clave

  • comprehensive medication management services
  • drug therapy problems
  • risk factors
  • pharmaceutical care
  • primary care
  • implementation stage
Acceso abierto

Influence of flavonoids’ lipophilicity on platelet aggregation

Publicado en línea: 21 Oct 2019
Páginas: 607 - 619

Resumen

Abstract

Flavonoids are natural polyphenolic compounds present in a wide spectrum of plants that have a beneficial effect on human health. In the context of cardiovascular diseases related to plaque and thrombus formation, flavonoids exhibit an anti-aggregatory effect. Previously, it has been reported that all tested flavonoids exhibit an antiaggregatory effect on platelet aggregation when measured by impedance aggregometry on whole blood, in the test of aggregation induced by adenosine diphosphate (ADP). As not all flavonoids have the same targets within signaling pathways, an assumption of a common non-specific mechanism related to lipophilicity is to be considered. To test this hypothesis, reverse-phase thin layer chromatography was used to assess the lipophilicity of flavonoids; impedance aggregometry was used for testing of platelet aggregation and flow cytometry to monitor the influence of flavonoids on platelet activation. Lipophilicity analysis showed a highly negative correlation of logP and MINaAC for groups of flavones and flavanones. As determined by flow cytometry, the exposition of receptors necessary for the promotion of platelet activation and primary clot formation was diminished, i.e., lowered expression of the activated form of integrin αIIbβ3 was observed in the presence of flavanone. Platelet membrane stabilization by flavonoids as a mechanism of antiaggregatory effect has been supported by impedance aggregometry experiments when specific inhibitors of platelet aggregation signaling pathways (U73122, indomethacin, verapamil) were used in the presence of a weak (ADP) and a strong (TRAP-6) agonist of aggregation. While individual flavonoids can have specific targets within aggregation signaling pathways, all flavonoids share a common non-specific mechanism of platelet aggregation inhibition related to their lipophilicity and membrane stabilization that, to some extent, contributes to their antiaggregatory effect.

Palabras clave

  • flavonoids
  • platelets
  • lipophilicity
  • flow cyto metry
  • antiaggregatory activity
Acceso abierto

In vitro evaluation of stearylamine cationic nanoemulsions for improved ocular drug delivery

Publicado en línea: 21 Oct 2019
Páginas: 621 - 634

Resumen

Abstract

Oil-in-water nanoemulsions (NEs) represent one of the formulation approaches to improve eye-related bio-availability of lipophilic drugs. The potential of cationic NEs is pronounced due to the electrostatic interaction of positively charged droplets with negatively charged mucins present in the tear film, providing prolonged formulation residence at the ocular surface. The aim of this study was to develop a cationic ophthalmic NE with cationic lipid stearylamine (SA) as a carrier of a positive charge. The addition of a nonionic surfactant provided the dual electro-steric stabilization of NEs and enabled tuning of SA concentration to achieve an optimal balance between its interaction with mucins and biocompatibility. Physicochemical characterization, stability profile, in vitro mucoadhesion study and biocompatibility study employing 3D HCE-T cell-based model of corneal epithelium pointed out the NE with 0.05 % (m/m) SA as the leading formulation. Minimizing SA content while retaining droplet/mucin interactions is of great importance for efficacy and safety of future ophthalmic drug products.

Palabras clave

  • cationic nanoemulsions
  • stearylamine
  • ophthalmic drug delivery
  • biocompatibility
  • mucoadhesion
Acceso abierto

Evaluation of stability and in vitro wound healing potential of melatonin loaded (lipid enriched) chitosan based microspheres

Publicado en línea: 21 Oct 2019
Páginas: 635 - 648

Resumen

Abstract

The aim of this study was to evaluate long-term stability and assess the wound healing potential of the innovative melatonin-loaded lipid-enriched hybrid system compared to conventional melatonin-loaded chitosan microspheres. The hybrid system contained nanostructured lipid carrier incorporated in the chitosan matrix, in order to modify melatonin release and alter physicochemical characteristics of the delivery system. Stability testing was performed during a six-month period under two conditions: refrigerated (5 ± 3 °C) and at room temperature (25 ± 2 °C/60 ± 5 % RH). Samples stored at both conditions were analyzed in terms of particle size, zeta potential, moisture content and thermal properties. At the end of testing, drug content was determined in all samples. Dressings wound healing potential was assessed by in vitro scratch test using human skin fibroblast cell line. Although both systems showed good stability characteristics, the addition of lipids in the system has improved its wound healing potential.

Palabras clave

  • melatonin
  • nanoparticles
  • microspheres
  • chitosan
  • stability
  • wound healing
Acceso abierto

Miniaturized shake-flask HPLC method for determination of distribution coefficient of drugs used in inflammatory bowel diseases

Publicado en línea: 21 Oct 2019
Páginas: 649 - 660

Resumen

Abstract

A new method for determination of distribution coefficient of drugs azathioprine, 6-mercaptopurine and 6-thioguanine and nutrient folic acid used in the treatment of inflammatory bowel disease based on a miniaturized shake-flask and HPLC/DAD was developed. Special attention was made to the most commonly reported problems in the measurement of distribution coefficients using a shake-flask method such as mixing technique, speed and time, the temperature of experiment, type of buffer and its pH as well as n-octanol/buffer phase ratio. The concentration of compounds in the buffer is determined by HPLC directly from shake flasks or conventional 2-mL vials. The developed method was fully validated according to ICH guidelines. Furthermore, experimental data were successfully compared with lipophilicity and human intestinal absorption calculated by the use of four different theoretical approaches. The method shows potential for high-throughput measurements of a large number of compounds.

Palabras clave

  • distribution coefficient logarithm
  • shake-flask
  • HPLC
  • inflammatory bowel disease
Acceso abierto

Antiproliferative evaluation of various aminoquinoline derivatives

Publicado en línea: 21 Oct 2019
Páginas: 661 - 672

Resumen

Abstract

Four classes of aminoquinoline derivatives were prepared: primaquine ureas 1af, primaquine bis-ureas 2af, chloroquine fumardiamides 3af and mefloquine fumardiamides 4af. Their antiproliferative activities against breast adeno-carcinoma (MCF-7), lung carcinoma (H460) and colon carcinoma (HCT 116 and SW620) cell lines were evaluated in vitro, using MTT cell proliferation assay. The results revealed a low activity of primaquine urea and bis-urea derivatives and high activity of all fumardiamides, with IC50 values in low micromolar range against all tested cancer cell lines.

Palabras clave

  • primaquine
  • chloroquine
  • mefloquine
  • fumardiamide
  • antiproliferative activity
Acceso abierto

Phenolic compounds of Iris adriatica and their antimycobacterial effects

Publicado en línea: 21 Oct 2019
Páginas: 673 - 681

Resumen

Abstract

Little is known about the pharmacological activities of Iris adriatica (Iridaceae), a plant endemic to Dalmatia (Croatia). We therefore performed a bioassay-guided fractionation including high-performance counter current chromatography (HPCCC) and antibacterial tests using Mycobacterium smegmatis mc2 155. One obtained fraction was found to be antimycobacterially active with a MIC of 64 mg L−1. Furthermore, fractions were tested for resistance modulatory effects using ethidium bromide as substrate. We were able to identify the pure isoflavonic compounds irigenin and irilone and a fraction containing mainly benzophenone 2,4,6-trihydroxy-4-methoxy-benzophenone, responsible for the resistance-modulatory activity of this plant.

Palabras clave

  • Radix Iridis
  • phenolic compounds
  • resistance modulation
  • ethidium bromide
  • MIC
Acceso abierto

Antiproliferative and genotoxic potential of xanthen-3-one derivatives

Publicado en línea: 21 Oct 2019
Páginas: 683 - 694

Resumen

Abstract

Twelve previously synthesized, biologically active 2,6,7-trihydroxyxanthen-3-one derivatives were evaluated in vitro for antiproliferative activity. Compounds were screened against HeLa, SW620, HepG2 and A549 tumor cell lines. Compound with the trifluormethyl group on C-4’ position of the phenyl ring showed the best inhibitory activity towards HeLa and A549 tumor cells with IC50 of 0.7 and 4.1 µmol L−1, resp. Compound with chlorine and fluorine substituents on aryl ring showed the best antiproliferative activity against SW620 with IC50 of 4.1 µmol L–1 and against HepG2 tumor cell line with IC50 of 4.2 µmol L–1. Analyses of cytotoxic and genotoxic potential of the trifluormethyl derivative were performed with cytokinesis-block micronucleus cytome assay in human lymphocyte culture and revealed no genotoxic and cytotoxic effects. The most potent compounds were subjected to molecular docking simulations in order to analyse bindings to molecular targets and, at the same time, further support the results of experimental cytotoxic tests. Docking studies showed sites of importance in forming hydrogen bonds of the most potent compounds with targets of interest.

Palabras clave

  • antiproliferative activity
  • genotoxic potential
  • docking study
  • xanthen-3-one derivatives
  • cytokinesis-block micronucleus cytome assay
Acceso abierto

Efficacy and safety of local lysozyme treatment in patients with oral mucositis after chemotherapy and radiotherapy

Publicado en línea: 21 Oct 2019
Páginas: 695 - 704

Resumen

Abstract

This observational clinical study was composed of two substudies: a non-comparative one (n = 166), testing only lysozyme-based compounds (LBCs), and a comparative substudy (n = 275), testing both LBCs and bicarbonate-based local compounds (BBCs) on the healing of oral mucositis during radio- or chemotherapy. The density of ulcerations has decreased significantly after the treatment with lysozyme in both substudies. The density of ulcerations in the radiotherapy group was lower in patients treated with LBCs compared to patients treated with BBCs (p < 0.001). In the chemotherapy group, reduction of ulceration density was similar with both LBCs and BBCs. The LBCs reduced pain intensity during the intake of solid food and speech more than BBCs in both patient cohorts (p < 0.05). In the radiotherapy cohort, pain intensity when consuming liquid foods was reduced more with LBCs than with BBCs (p < 0.05). No adverse events were recorded. This study demonstrates the advantages of treating oral mucositis during radiotherapy or chemo-therapy with LBCs.

Palabras clave

  • oral mucositis
  • treatment efficacy
  • radiotherapy
  • chemotherapy
  • topical
  • lysozyme

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