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Rare disease day in Slovakia, Europlan national conference

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Conference abstracts, Rare disease day, conference 29.2.2012, First Slovak conference about rare diseases

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Clinical Pharmacy in the Slovak Republic, dedicated to the associated professor Lívia Magulová, PhD.

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Revista
eISSN
2453-6725
Publicado por primera vez
25 Nov 2011
Periodo de publicación
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Volumen 67 (2020): Edición 1 (January 2020)

Detalles de la revista
Formato
Revista
eISSN
2453-6725
Publicado por primera vez
25 Nov 2011
Periodo de publicación
2 veces al año
Idiomas
Inglés

Buscar

6 Artículos
access type Acceso abierto

Chitosan Hydrogel Improves Bioavailability of Megosin

Publicado en línea: 18 Nov 2020
Páginas: 1 - 6

Resumen

AbstractBackground

The aim of this study was to obtain chitosan hydrogels containing megosin, an antiviral medicinal substance, to prolong its bioavailability. Megosin as an immunomodulating agent possesses at least twice higher virostatic and virucidal activities than gossypol, the megosin precursor, and other imine derivatives of gossypol.

Materials and Methods

Chitosan, used in this paper, was obtained by deacetylation of chitin; megosin was obtained on the bases of gossypol. Different concentrations of sodium tripolyphosphate (STPP) were used as the cross-linking agent. The release of megosin from hydrogel samples into blood was conducted on five white rats in four groups.

Results

Infrared spectral data demonstrated cross-linkage that the band responsible for NH bending of the uncross-linked chitosan reduced its intensity and moved to a lower wavelength, 1636 cm−1. It has been proven that megosin contained in gels does not penetrate into the blood and organs after vaginal administration. Release kinetics of megosin from chitosan hydrogels revealed that within 7 h, up to 52% of megosin is allowed into acidic solution (pH 4.5).

Conclusion

This study demonstrates the possibility to prolong bioavailability of megosin for at least 7 h, during which time it is not released into blood. The obtained results show the possibility to use the gel composition to treat vaginal herpes.

Palabras clave

  • Chitosan hydrogel
  • megosin
  • vaginal herpes
access type Acceso abierto

Synthesis, antibacterial and free radical scavenging activity of some newer N-((10-nitro-1H-indolo [1, 2-c]quinazolin-12-yl)methylene)benzenamines

Publicado en línea: 18 Nov 2020
Páginas: 7 - 16

Resumen

Abstract

Present research is oriented on the synthesis of some novel 12-(N-arylmethaniminyl)indolo[1,2-c]quinazoline analogs (4b1–4b11) and their characterization by 1H NMR, 13C NMR, FTIR and mass spectrophotometry. Their free radical scavenging activity and antibacterial potential were also evaluated. Many derivatives have shown a marked free radical scavenging capacity in all the concentrations but specifically compounds 4b7, 4b8 and 4b11 have shown good antioxidant potential with an IC50 value of 25.18 μmol/L, 28.09 μmol/L & 44.22 μmol/L, respectively (DPPH method) and 39.46 μmol/L, 44.47 μmol/L & 35.61 μmol/L, respectively (H2O2 method). The antibacterial evaluation was carried out against B. subtilis and E. coli by agar well diffusion method and it revealed that all the compounds in the series were having marked antibacterial activity but compounds 4b9 and 4b11 have shown best antibacterial potential. Then, it was concluded that the derivatives which were containing substituted anilines (4-Nitro, 4-Fluoro, 4-Bromo & 4-Chloro-2-nitro) on the carbon attached on the 12th position of indoloquinazoline moiety were having marked potential as an antibacterial and free radical scavenger.

Palabras clave

  • free radical scavenger
  • antibacterial
  • DPPH
  • indoloquinazoline
  • IC
access type Acceso abierto

Concentration-dependent effect of silymarin on concanavalin A-stimulated mouse spleen cells in vitro

Publicado en línea: 18 Nov 2020
Páginas: 17 - 26

Resumen

AbstractAims

Silymarin (SIL), a mixture of phenolic compounds, has a pleiotropic mode of action on various cell types, including immune cells. In this study, we investigated the concentration-dependent effect of SIL on proliferation of concanavalin A (CoA)-stimulated mouse spleen T lymphocytes, their viability, and secretion of IFN-g and IL-4 cytokines ex vivo in relation to gene expressions of transcription factors nuclear factor kappa B and Foxp3. In addition, metabolic activity of T cells was determined as changes in the mitochondrial membrane potential and apoptosis.

Material/Methods

Isolated splenocytes were stimulated with lectin CoA and treated with SIL atthe concentrations of 5, 10, 20, and 40 μg/ml for 70 h and unstimulated cells served as the control. Cultures of splenocytes were evaluated for proliferation index following BrdU incorporation and viability of cells after trypan blue staining. Gene expressions of transcription factors and cytokines were assessed using real-time PCR, whereas ELISA test was applied to measure cytokine secretion. Mitochondrial membrane potential and apoptosis were determined by flow cytometry.

Results

We demonstrated that CoA-activated mouse spleen T lymphocytes show different susceptibilities to low (£10 μg/ml) and higher (20 and 40 μg/ml) SIL concentrations. Low concentrations resulted in increased proliferation, cytokine secretion, and mitochondrial membrane potential and reduced transition of cells to apoptosis. High concentration of SIL had the opposite effect without exerting significant cytotoxicity and upregulated genes for cytokines and transcription factors on mRNA level. It is possible that individual subpopulations of T cells induced by CoA were differentially affected by the various SIL concentrations and the dose of 40 μg/ml had the profound suppressive effect. This correlated with the highest expression of Foxp3 factor, indicating that this dose stimulated preferential differentiation to Tregs lymphocytes.

Conclusions

Treatment with suitable doses of SIL can provide potential benefits in the modulation of host immune functions in various diseases.

Palabras clave

  • silymarin
  • mouse
  • splenocytes
  • proliferation
  • mitochondrial potential
  • apoptosis
access type Acceso abierto

Study of qualitative and quantitative content of amino acids in pumpkin seeds for further standardization of the herbal drug

Publicado en línea: 18 Nov 2020
Páginas: 27 - 32

Resumen

AbstractAim

Literary sources on qualitative composition, quantitative content of biologically active substances, and standardization methods of pumpkin seeds have been studied. It has been established that, along with Δ7-sterols, whose action is associated with treatment of the prostate gland, pumpkin seeds contain amino acids, cucurbitin in particular, which are responsible for their antihelminthic effect. The aim is to study the qualitative and quantitative content of amino acids in domestic samples of pumpkin seeds in order to clarify the possibility of pumpkin seed standardization for this class of biologically active substances.

Methods

The investigation of the possibility of amino acids’ identification in the herbal drug by the thin-layer chromatography (TLC) method was carried out on silica gel 60 F254 plates, Merck and Silica gel 60, Merck, on aluminum and glass supports in a mixture of the following solvents: butanol–acetone–acetic acid–water (35:35:10:20). The conclusions have been made based on the presence of characteristic zones of amino acids in the chromatograms after the treatment with ninhydrin solution.

Quantitative determination of amino acids in the herbal drug was carried out by absorption spectrometry using HP spectrophotometer HP-8453 UV-VIS, Hewlett Packard (USA).

Results

The chromatographic profile of the amino acid fraction of domestic samples of pumpkin seeds was studied using a TLC technique. In the chromatograms of test solutions from all samples, the zones were detected at the level of histidine, aspartic acid, glutamic acid, glycine, and leucine zones, as well as a zone with color (olive) that differs from the other zones of amino acids and which is possibly a zone of cucurbitin.

On the basis of the results of qualitative research, the quantitative content of the sum of amino acids according to a UV method developed has been determined, which including purification from the fatty oil, further extraction with an aqueous alcohol solution, selection of aliquots for the reaction with ninhydrin solution, and subsequent determination of the absorbance of the test solution and the solution of glutamic acid at a wavelength of 400 nm.

It has been established that the content of the sum of amino acids expressed as glutamic acid in domestic samples is about 2%.

Conclusions

The research of the possibility of pumpkin seed standardization by the content of amino acids was carried out. The chromatographic profile of the amino acid fraction of domestic samples of pumpkin seeds was studied using a TLC method developed. The quantitative content of the amino acids sum by the absorption spectrophotometry method was investigated. The techniques developed will be recommended for inclusion in the draft of national monograph “Pumpkin seeds.”

Palabras clave

  • pumpkin seeds
  • amino acids
  • TLC method
  • UV-vis spectrophotometry method
  • standardization
  • SPhU
access type Acceso abierto

Therapeutic Drug Monitoring of Venlafaxine and Impact of Age, Gender, BMI, and Diagnosis

Publicado en línea: 18 Nov 2020
Páginas: 33 - 37

Resumen

Abstract

Depression is a common mental disorder affecting more than 264 million people in the world and 5.1% of the Slovak population. Although various antidepressant approaches have been used; still, about 40% of patients do not respond to a first-choice drug administration and one third of patients do not achieve total remission. Therapeutic drug monitoring (TDM) is a method used for quantification and interpreting the drug concentrations in plasma in order to optimize the pharmacotherapy. The aim of this study was to measure the plasma concentrations of venlafaxine, the fourth most prescribed antidepressant in Slovakia, as well as its active metabolite and interpret them with the relevant patients’ characteristics.

The study was of retrospective nature and 28 adult patients in total were included. The concentrations of venlafaxine and its active metabolite O-desmethylvenlafaxine (ODV) in plasma were quantified using the validated UHPLC-MS/MS method. The effects of potential influencing factors were evaluated by a multivariate linear regression model.

Only 39% of patients reached the venlafaxine active moiety concentrations within the recommended therapeutic range. Plasma concentrations were dependent on age, gender, and duration of the therapy. Venlafaxine metabolism expressed as a metaboliteto-parent concentrations ratio was influenced by a combination of age, gender, and body mass index (BMI). We did not observe any significant difference in plasma concentrations between the patients with a single and recurrent diagnosis of depression. Combining variables made an additive effect on plasma concentrations, for example, active moiety plasma concentrations were higher in older women. In contrast, drug metabolism was higher in older men and men with lower BMI. TDM of venlafaxine is recommended in clinical practice, especially in the elderly when beginning the pharmacotherapy.

Palabras clave

  • Venlafaxine
  • major depressive disorder
  • therapeutic drug monitoring
access type Acceso abierto

Comparative morphological studies of raw parts of the most common species of Thymus in Ukraine

Publicado en línea: 18 Nov 2020
Páginas: 38 - 45

Resumen

Abstract

This study presents the results of our comparative evaluation of diagnostic morphological characteristics of raw material from 11 species of genus Thymus L. of medicinal and raw material importance occurring in Ukraine. The following taxa were evaluated: T. serpyllum L., T. odoratissimus Mill. (T. glabrescens Willd.), T. borysthenicus Klokov & Des.-Shost., T. pallasianus Heinr. Braun, T. moldavicus Klokov & Des.-Shost., T. calcareus Klokov & Des.-Shost., T. alpestris Tausch ex A. Kern., T. × dimorphus Klokov & Des.-Shost., T. pannonicus All. s.l. (including T. marschallianus Willd.), T. pulegioides L. and T. roegneri K. Koch (T. alternans Klokov). Among wild species of thyme, only raw material of Thymus serpyllum is officially allowed for use with the purpose for production of pharmaceuticals and medicines. A comparison of the main characteristics is particularly important in view of the fact that raw material is represented by parts of plants (stems, leaves and flowers), which makes any whole comparison of species hardly possible. This study has revealed that stem pubescence, calyx structure, configuration/arrangement and type of leaf venation can provide valuable information for diagnostics of raw material of Thymus species. The results exhibited that according to characters of stem pubescence, calyx structure, shape and size of leaves the most similar are raw material samples of T. serpyllum and T. moldavicus. However, these species are rather well separated geographically, so the possibility of mixing of their raw material is negligible. Other species have significant morphological differences in certain characteristics by which they can be diagnosed in the raw material.

Palabras clave

  • Thymus
  • morphology
  • characters
  • raw material
  • medicinal plants
  • Ukraine
6 Artículos
access type Acceso abierto

Chitosan Hydrogel Improves Bioavailability of Megosin

Publicado en línea: 18 Nov 2020
Páginas: 1 - 6

Resumen

AbstractBackground

The aim of this study was to obtain chitosan hydrogels containing megosin, an antiviral medicinal substance, to prolong its bioavailability. Megosin as an immunomodulating agent possesses at least twice higher virostatic and virucidal activities than gossypol, the megosin precursor, and other imine derivatives of gossypol.

Materials and Methods

Chitosan, used in this paper, was obtained by deacetylation of chitin; megosin was obtained on the bases of gossypol. Different concentrations of sodium tripolyphosphate (STPP) were used as the cross-linking agent. The release of megosin from hydrogel samples into blood was conducted on five white rats in four groups.

Results

Infrared spectral data demonstrated cross-linkage that the band responsible for NH bending of the uncross-linked chitosan reduced its intensity and moved to a lower wavelength, 1636 cm−1. It has been proven that megosin contained in gels does not penetrate into the blood and organs after vaginal administration. Release kinetics of megosin from chitosan hydrogels revealed that within 7 h, up to 52% of megosin is allowed into acidic solution (pH 4.5).

Conclusion

This study demonstrates the possibility to prolong bioavailability of megosin for at least 7 h, during which time it is not released into blood. The obtained results show the possibility to use the gel composition to treat vaginal herpes.

Palabras clave

  • Chitosan hydrogel
  • megosin
  • vaginal herpes
access type Acceso abierto

Synthesis, antibacterial and free radical scavenging activity of some newer N-((10-nitro-1H-indolo [1, 2-c]quinazolin-12-yl)methylene)benzenamines

Publicado en línea: 18 Nov 2020
Páginas: 7 - 16

Resumen

Abstract

Present research is oriented on the synthesis of some novel 12-(N-arylmethaniminyl)indolo[1,2-c]quinazoline analogs (4b1–4b11) and their characterization by 1H NMR, 13C NMR, FTIR and mass spectrophotometry. Their free radical scavenging activity and antibacterial potential were also evaluated. Many derivatives have shown a marked free radical scavenging capacity in all the concentrations but specifically compounds 4b7, 4b8 and 4b11 have shown good antioxidant potential with an IC50 value of 25.18 μmol/L, 28.09 μmol/L & 44.22 μmol/L, respectively (DPPH method) and 39.46 μmol/L, 44.47 μmol/L & 35.61 μmol/L, respectively (H2O2 method). The antibacterial evaluation was carried out against B. subtilis and E. coli by agar well diffusion method and it revealed that all the compounds in the series were having marked antibacterial activity but compounds 4b9 and 4b11 have shown best antibacterial potential. Then, it was concluded that the derivatives which were containing substituted anilines (4-Nitro, 4-Fluoro, 4-Bromo & 4-Chloro-2-nitro) on the carbon attached on the 12th position of indoloquinazoline moiety were having marked potential as an antibacterial and free radical scavenger.

Palabras clave

  • free radical scavenger
  • antibacterial
  • DPPH
  • indoloquinazoline
  • IC
access type Acceso abierto

Concentration-dependent effect of silymarin on concanavalin A-stimulated mouse spleen cells in vitro

Publicado en línea: 18 Nov 2020
Páginas: 17 - 26

Resumen

AbstractAims

Silymarin (SIL), a mixture of phenolic compounds, has a pleiotropic mode of action on various cell types, including immune cells. In this study, we investigated the concentration-dependent effect of SIL on proliferation of concanavalin A (CoA)-stimulated mouse spleen T lymphocytes, their viability, and secretion of IFN-g and IL-4 cytokines ex vivo in relation to gene expressions of transcription factors nuclear factor kappa B and Foxp3. In addition, metabolic activity of T cells was determined as changes in the mitochondrial membrane potential and apoptosis.

Material/Methods

Isolated splenocytes were stimulated with lectin CoA and treated with SIL atthe concentrations of 5, 10, 20, and 40 μg/ml for 70 h and unstimulated cells served as the control. Cultures of splenocytes were evaluated for proliferation index following BrdU incorporation and viability of cells after trypan blue staining. Gene expressions of transcription factors and cytokines were assessed using real-time PCR, whereas ELISA test was applied to measure cytokine secretion. Mitochondrial membrane potential and apoptosis were determined by flow cytometry.

Results

We demonstrated that CoA-activated mouse spleen T lymphocytes show different susceptibilities to low (£10 μg/ml) and higher (20 and 40 μg/ml) SIL concentrations. Low concentrations resulted in increased proliferation, cytokine secretion, and mitochondrial membrane potential and reduced transition of cells to apoptosis. High concentration of SIL had the opposite effect without exerting significant cytotoxicity and upregulated genes for cytokines and transcription factors on mRNA level. It is possible that individual subpopulations of T cells induced by CoA were differentially affected by the various SIL concentrations and the dose of 40 μg/ml had the profound suppressive effect. This correlated with the highest expression of Foxp3 factor, indicating that this dose stimulated preferential differentiation to Tregs lymphocytes.

Conclusions

Treatment with suitable doses of SIL can provide potential benefits in the modulation of host immune functions in various diseases.

Palabras clave

  • silymarin
  • mouse
  • splenocytes
  • proliferation
  • mitochondrial potential
  • apoptosis
access type Acceso abierto

Study of qualitative and quantitative content of amino acids in pumpkin seeds for further standardization of the herbal drug

Publicado en línea: 18 Nov 2020
Páginas: 27 - 32

Resumen

AbstractAim

Literary sources on qualitative composition, quantitative content of biologically active substances, and standardization methods of pumpkin seeds have been studied. It has been established that, along with Δ7-sterols, whose action is associated with treatment of the prostate gland, pumpkin seeds contain amino acids, cucurbitin in particular, which are responsible for their antihelminthic effect. The aim is to study the qualitative and quantitative content of amino acids in domestic samples of pumpkin seeds in order to clarify the possibility of pumpkin seed standardization for this class of biologically active substances.

Methods

The investigation of the possibility of amino acids’ identification in the herbal drug by the thin-layer chromatography (TLC) method was carried out on silica gel 60 F254 plates, Merck and Silica gel 60, Merck, on aluminum and glass supports in a mixture of the following solvents: butanol–acetone–acetic acid–water (35:35:10:20). The conclusions have been made based on the presence of characteristic zones of amino acids in the chromatograms after the treatment with ninhydrin solution.

Quantitative determination of amino acids in the herbal drug was carried out by absorption spectrometry using HP spectrophotometer HP-8453 UV-VIS, Hewlett Packard (USA).

Results

The chromatographic profile of the amino acid fraction of domestic samples of pumpkin seeds was studied using a TLC technique. In the chromatograms of test solutions from all samples, the zones were detected at the level of histidine, aspartic acid, glutamic acid, glycine, and leucine zones, as well as a zone with color (olive) that differs from the other zones of amino acids and which is possibly a zone of cucurbitin.

On the basis of the results of qualitative research, the quantitative content of the sum of amino acids according to a UV method developed has been determined, which including purification from the fatty oil, further extraction with an aqueous alcohol solution, selection of aliquots for the reaction with ninhydrin solution, and subsequent determination of the absorbance of the test solution and the solution of glutamic acid at a wavelength of 400 nm.

It has been established that the content of the sum of amino acids expressed as glutamic acid in domestic samples is about 2%.

Conclusions

The research of the possibility of pumpkin seed standardization by the content of amino acids was carried out. The chromatographic profile of the amino acid fraction of domestic samples of pumpkin seeds was studied using a TLC method developed. The quantitative content of the amino acids sum by the absorption spectrophotometry method was investigated. The techniques developed will be recommended for inclusion in the draft of national monograph “Pumpkin seeds.”

Palabras clave

  • pumpkin seeds
  • amino acids
  • TLC method
  • UV-vis spectrophotometry method
  • standardization
  • SPhU
access type Acceso abierto

Therapeutic Drug Monitoring of Venlafaxine and Impact of Age, Gender, BMI, and Diagnosis

Publicado en línea: 18 Nov 2020
Páginas: 33 - 37

Resumen

Abstract

Depression is a common mental disorder affecting more than 264 million people in the world and 5.1% of the Slovak population. Although various antidepressant approaches have been used; still, about 40% of patients do not respond to a first-choice drug administration and one third of patients do not achieve total remission. Therapeutic drug monitoring (TDM) is a method used for quantification and interpreting the drug concentrations in plasma in order to optimize the pharmacotherapy. The aim of this study was to measure the plasma concentrations of venlafaxine, the fourth most prescribed antidepressant in Slovakia, as well as its active metabolite and interpret them with the relevant patients’ characteristics.

The study was of retrospective nature and 28 adult patients in total were included. The concentrations of venlafaxine and its active metabolite O-desmethylvenlafaxine (ODV) in plasma were quantified using the validated UHPLC-MS/MS method. The effects of potential influencing factors were evaluated by a multivariate linear regression model.

Only 39% of patients reached the venlafaxine active moiety concentrations within the recommended therapeutic range. Plasma concentrations were dependent on age, gender, and duration of the therapy. Venlafaxine metabolism expressed as a metaboliteto-parent concentrations ratio was influenced by a combination of age, gender, and body mass index (BMI). We did not observe any significant difference in plasma concentrations between the patients with a single and recurrent diagnosis of depression. Combining variables made an additive effect on plasma concentrations, for example, active moiety plasma concentrations were higher in older women. In contrast, drug metabolism was higher in older men and men with lower BMI. TDM of venlafaxine is recommended in clinical practice, especially in the elderly when beginning the pharmacotherapy.

Palabras clave

  • Venlafaxine
  • major depressive disorder
  • therapeutic drug monitoring
access type Acceso abierto

Comparative morphological studies of raw parts of the most common species of Thymus in Ukraine

Publicado en línea: 18 Nov 2020
Páginas: 38 - 45

Resumen

Abstract

This study presents the results of our comparative evaluation of diagnostic morphological characteristics of raw material from 11 species of genus Thymus L. of medicinal and raw material importance occurring in Ukraine. The following taxa were evaluated: T. serpyllum L., T. odoratissimus Mill. (T. glabrescens Willd.), T. borysthenicus Klokov & Des.-Shost., T. pallasianus Heinr. Braun, T. moldavicus Klokov & Des.-Shost., T. calcareus Klokov & Des.-Shost., T. alpestris Tausch ex A. Kern., T. × dimorphus Klokov & Des.-Shost., T. pannonicus All. s.l. (including T. marschallianus Willd.), T. pulegioides L. and T. roegneri K. Koch (T. alternans Klokov). Among wild species of thyme, only raw material of Thymus serpyllum is officially allowed for use with the purpose for production of pharmaceuticals and medicines. A comparison of the main characteristics is particularly important in view of the fact that raw material is represented by parts of plants (stems, leaves and flowers), which makes any whole comparison of species hardly possible. This study has revealed that stem pubescence, calyx structure, configuration/arrangement and type of leaf venation can provide valuable information for diagnostics of raw material of Thymus species. The results exhibited that according to characters of stem pubescence, calyx structure, shape and size of leaves the most similar are raw material samples of T. serpyllum and T. moldavicus. However, these species are rather well separated geographically, so the possibility of mixing of their raw material is negligible. Other species have significant morphological differences in certain characteristics by which they can be diagnosed in the raw material.

Palabras clave

  • Thymus
  • morphology
  • characters
  • raw material
  • medicinal plants
  • Ukraine

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