RESUMO
Cytostatic and pro-apoptotic effects of selenium steroid derivatives against HeLa cells were determined. The highest cytostatic activity was shown by derivative 4 (GI50 25.0 µM, almost complete growth inhibition after three days of culture, and over 97% of apoptotic and dead cells at 200 µM). The results of our study (cell number measurements, apoptosis profile, relative expression of apoptosis-related APAF1, BID, and mevalonate pathway-involved HMGCR, SQLE, CYP51A1, and PDHB genes, and computational chemistry data) support the hypothesis that tested selenosteroids induce the extrinsic pathway of apoptosis by affecting the cell membrane as cholesterol antimetabolites. An additional mechanism of action is possible through a direct action of derivative 4 to inhibit PDHB expression in a way similar to steroid hormones.
Assuntos
Citostáticos , Humanos , Células HeLa , Citostáticos/farmacologia , Apoptose , Colesterol/metabolismoRESUMO
With increasing number of immunocompromised patients as well as drug resistance in fungi, the risk of fatal fungal infections in humans increases as well. The action of echinocandins is based on the inhibition of ß-(1,3)-d-glucan synthesis that builds the fungal cell wall. Caspofungin, micafungin, anidulafungin and rezafungin are semi-synthetic cyclic lipopeptides. Their specific chemical structure possess a potential to obtain novel derivatives with better pharmacological properties resulting in more effective treatment, especially in infections caused by Candida and Aspergillus species. In this review we summarise information about echinocandins with closer look on their chemical structure, mechanism of action, drug resistance and usage in clinical practice. We also introduce actual trends in modification of this antifungals as well as new methods of their administration, and additional use in viral and bacterial infections.
Assuntos
Antifúngicos/farmacologia , Aspergillus/efeitos dos fármacos , Candida/efeitos dos fármacos , Desenho de Fármacos , Equinocandinas/farmacologia , Antifúngicos/química , Aspergillus/metabolismo , Candida/metabolismo , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Equinocandinas/química , Glucanos/antagonistas & inibidores , Glucanos/metabolismo , Testes de Sensibilidade Microbiana , Estrutura MolecularRESUMO
Oxythiamine (OT) and 3-deazathiamine (DAT) are the antimetabolites of thiamine. The aim of study was to compare the effects of OT and DAT pyrophosphates (-PP) on the kinetics of mammalian pyruvate dehydrogenase complex (PDHC) and the in vitro culture of HeLa cells. The kinetic study showed that 3-deazathiamine pyrophosphate (DATPP) was a much stronger competitive inhibitor (Ki = 0.0026 µM) of PDHC than OTPP (Ki = 0.025 µM). Both Ki values were much lower versus K m for thiamine pyrophosphate (0.06 µM). However, DATPP added to the culture medium for the HeLa cells culture did not hamper the rate of cell growth and showed not significant impact on the viability of the cells, whereas OTPP and OT showed a significant cytostatic effect. The differences between the thiamine antivitamins in their effect on cell growth in vitro may be due to differences in physicochemical properties and difficulty in DAT transport across the cell membrane.
Assuntos
Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Complexo Piruvato Desidrogenase/antagonistas & inibidores , Tiamina/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Células HeLa , Humanos , Estrutura Molecular , Complexo Piruvato Desidrogenase/metabolismo , Relação Estrutura-Atividade , Tiamina/análogos & derivados , Tiamina/química , Células Tumorais CultivadasRESUMO
Malassezia pachydermatis causes infections of the skin and mucous membranes, especially in individuals with metabolic, hormonal, and immunological disorders. The search for M. pachydermatis properties that differentiate isolates from healthy and infected animals may result in the identification of typically commensal and potentially pathogenic strains within the entire species. We aimed to determine and compare protein profiles of M. pachydermatis strains isolated from 30 dogs with clinical symptoms of otitis externa and 34 dogs without symptoms of any disease. Two-dimensional gel electrophoresis was applied, and proteins distinguishing the two groups of strains were identified by liquid chromatography coupled with tandem mass spectrometry. Significant differences were found between potentially pathogenic and commensal isolates. The most significant finding was the presence of nicotinamide adenine dinucleotide phosphate (NADP)-dependent mannitol dehydrogenase and ketol-acid reductoisomerase among M. pachydermatis strains obtained from dogs with otitis externa. Nevertheless, it is not clear whether they are associated directly with the pathogenicity or they play the role of fungal allergen. On the basis of these findings, we can conclude that there may be two distinct groups of M. pachydermatis strains-one typically commensal and the other with properties that enhance the infection process. These results may be used for more precise diagnosis and identification of potentially pathogenic strains in the future.
Assuntos
Dermatomicoses/veterinária , Doenças do Cão , Otite Externa/microbiologia , Animais , Dermatomicoses/diagnóstico , Dermatomicoses/microbiologia , Dermatomicoses/terapia , Doenças do Cão/diagnóstico , Doenças do Cão/microbiologia , Doenças do Cão/terapia , Cães , Eletroforese em Gel Bidimensional , Proteínas Fúngicas , Malassezia/classificação , Malassezia/metabolismo , Malassezia/patogenicidade , Otite Externa/diagnóstico , Otite Externa/terapiaRESUMO
BACKGROUND: Malassezia pachydermatis is an opportunistic yeast involved in skin and ear canal infections of dogs and cats. Reports suggest that strains of M. pachydermatis resistant to commonly used antifungal agents may be emerging. Therefore, new therapeutic strategies should be explored. OBJECTIVES: The synergistic effect of oxythiamine (OT) and ketoconazole (KTC) was analysed using a reference strain and field isolates (n = 66) of M. pachydermatis. Hydrogel formulations containing these components also were evaluated. METHODS AND MATERIALS: The minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) of OT, KTC and their mixtures were determined by a broth macrodilution method. The antifungal effects of hydrogel formulations were determined by a plate diffusion method. RESULTS: The MIC and MFC values of OT were in the range 0.08 × 103 to 10 × 103 mg/L. All M. pachydermatis strains showed higher susceptibility to KTC (MICs and MFCs in the range 0.04-0.32 mg/L). Formulations that combined OT and KTC showed a synergistic effect for all tested isolates (n = 66). Hydrogels that contained OT at a concentration of 10 × 103 or 20 × 103 mg/L and KTC at the concentration of 0.1 × 103 mg/L showed a stronger effect than a commercially available product with KTC alone (20 × 103 mg/L). CONCLUSIONS AND CLINICAL IMPORTANCE: Synergy of these drugs may allow for successful topical treatment which utilizes lower doses of KTC without changing its therapeutic effectiveness. Hydrogel formulations proved to be attractive drug carriers for potential topical use.
Assuntos
Antifúngicos/uso terapêutico , Dermatomicoses/veterinária , Doenças do Cão/microbiologia , Cetoconazol/uso terapêutico , Malassezia , Otite Externa/veterinária , Oxitiamina/uso terapêutico , Animais , Antifúngicos/administração & dosagem , Dermatomicoses/tratamento farmacológico , Doenças do Cão/tratamento farmacológico , Cães , Sinergismo Farmacológico , Quimioterapia Combinada , Hidrogel de Polietilenoglicol-Dimetacrilato/administração & dosagem , Cetoconazol/administração & dosagem , Malassezia/efeitos dos fármacos , Testes de Sensibilidade Microbiana/veterinária , Otite Externa/tratamento farmacológico , Otite Externa/microbiologia , Oxitiamina/administração & dosagemRESUMO
Malassezia pachydermatis causes infections of the skin and mucous membranes, especially in animals. It is commonly accepted that symptom manifestation depends on the physiological status of the host (different metabolic, hormonal, and immunological disorders). However, it should be considered whether distinct strains of M. pachydermatis could have different pathogenic potential and maintain opposite relations with the host, such as commensalism or parasitism. The scope of this study was to explore the population structure, genetic diversity, and phylogenetic relationships of M. pachydermatis strains isolated from dogs with clinical symptoms of otitis externa and from healthy dogs in order to investigate their relationships and evolutionary history. For all tests, a group of 30 strains derived from dogs with otitis externa and 34 strains from healthy dogs were used. The level of genetic diversity was initially assessed by polymerase chain reaction (PCR)-based random amplification of polymorphic DNA (RAPD-PCR), whereas evolutionary history was assessed by comparison of the nucleotide sequences of the internal transcribed spacer ITS1 region of nuclear rDNA. RAPD-PCR fingerprinting revealed a high level of genetic polymorphism in both tested groups (85% of unique profiles), but clinical isolates usually grouped together with other strains from otitis externa cases. Sequencing analysis identified 17 distinct genotypes with 59 polymorphic sites within both populations; however, putatively virulent strains were more closely related, indicating a probable correlation between the genotype and the virulence potential. Therefore, the hypothesis that M. pachydermatis virulence depends solely on the host's properties should be reconsidered including evolutionary and epidemiological data.
Assuntos
Doenças do Cão/microbiologia , Variação Genética , Malassezia/genética , Malassezia/patogenicidade , Otite Externa/veterinária , Animais , DNA Intergênico , DNA Ribossômico , Doenças do Cão/epidemiologia , Cães/microbiologia , Genótipo , Malassezia/isolamento & purificação , Malassezia/fisiologia , Otite Externa/epidemiologia , Otite Externa/microbiologia , Filogenia , Reação em Cadeia da Polimerase , Polimorfismo Genético , Técnica de Amplificação ao Acaso de DNA Polimórfico , Simbiose , VirulênciaRESUMO
Gram-positive rods Bacillus cereus sensu lato (sl) are common in natural habitats and food products. It is believed that they are restricted to spores; however, their ecology in aquatic habitats is still poorly investigated. Thus, the aim of the study was to assess the rain-dependent fluctuations in the concentration of B. cereus sl vegetative cells and spores, with evaluation of their phylogenetic and population structure in relation to the toxicity and psychrotolerance. We proved that vegetative cells of B. cereus sl are widely distributed in fresh water of rivers and lakes, being as common as spores. Moreover, heavy rain has a huge impact on their concentration in undisturbed environments. The diversity of B. cereus sl reflects the multiple sources of bacteria and the differences between their distinct environments. Next, their diverse genetic structure and phenotypes better fit their ecological properties than their taxonomic affiliation.
Assuntos
Bacillus cereus/fisiologia , Água Doce/microbiologia , Variação Genética , Esporos Bacterianos/fisiologia , Bacillus cereus/classificação , Bacillus cereus/genética , Bacillus cereus/isolamento & purificação , Fenótipo , Filogenia , Polônia , Esporos Bacterianos/isolamento & purificaçãoRESUMO
Quinolinic acid (QUIN), one of the end metabolites in the kynurenine pathway, plays an important role in the pathogenesis of several diseases. Serum QUIN concentration rises in patients with renal dysfunction, liver cirrhosis, and many other inflammatory diseases. In the present study, osmotic minipumps containing QUIN (0.3 and 1mg/day) were implanted intraperitoneally into rats for 28days. Then, the physiological and toxicological variables were evaluated and LC-QTOF-MS serum metabolic fingerprinting was performed. QUIN significantly decreased the serum concentrations of several amino acids (phenylalanine, valine, tyrosine, and tryptophan), pantothenic acid, branched chain C4 acylcarnitine, total cholesterol, and glucose; increased the serum concentrations of amides (pentadecanoic amide, palmitic amide, oleamide, and stearamide), polyamines (spermine and spermidine), sphingosine, and deoxy-prostaglandin; caused alterations in phospholipids. This is the first report of comprehensive metabolites analysis after chronic intraperitoneal administration of QUIN. Further studies could develop new therapeutics for patients with disorders accompanied by increased serum level of QUIN.
Assuntos
Metabolômica , Ácido Quinolínico/farmacologia , Animais , Bombas de Infusão , Infusões Parenterais , Masculino , RatosRESUMO
Propolis has been used since ancient times in folk medicine. It is a popular medicine possessing a broad spectrum of biological activities. This material is one of the richest sources of polyphenolic compounds such as flavonoids and phenolic acids. The ethanolic extract of propolis (EEP) evokes antibacterial, antiviral, antifungal and anticancer properties. Due to pharmacological properties it is used in the commercial production of nutritional supplements. In this study, gas chromatography coupled with mass spectrometry (GC-MS) was used to quantify main polyphenols in EEPs. The effect of EEPs, individual EEPs components (chrysin, galangin, pinocembrin, caffeic acid, p-coumaric acid, ferulic acid) and their mixture on viability of human tongue squamous cell carcinoma cell line (CAL-27) as well as the molecular mechanisms of the process were examined. The results of MTTs assay demonstrated that EEP, polyphenols and mixture of polyphenolic compounds were cytotoxic for CAL-27 cells in a dose dependent manner. The mechanism of cytotoxicity induced by these components undergoes through apoptosis as detected by flow cytometry. The ethanolic extracts of propolis activated caspases -3, -8, -9. Mixture of polyphenols was found as the most potent inducer of apoptosis thorough both intrinsic and extrinsic pathway. Therefore, we suggest that anticancer properties of propolis is related to synergistic activity of its main components.
Assuntos
Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/patologia , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Própole/química , Neoplasias da Língua/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Neoplasias da Língua/tratamento farmacológico , Células Tumorais CultivadasRESUMO
High profitability and simplicity of direct compression, encourages pharmaceutical industry to create universal excipients to improve technology process. Prosolv® SMCC - silicified microcrystalline cellulose and Starch 1500® - pregelatinized starch, are the example of multifunctional excipients. The aim of the present study was to evaluate the stability of theophylline (API) in the mixtures with excipients with various physico-chemical properties (Prosolv® SMCC 90, Prosolv® SMCC HD 90, Prosolv* SMCC 50®, Starch 1500® and magnesium stearate). The study presents results of thermal analysis of the mixtures with theophylline before and after 6 months storage of the tablets at various temperatures and relative humidity conditions (25 ± 2°C/40 ± 5% RH, 40 ± 2°C/75 ± 5% RH). It was shown that high concentration of Starch 1500® (49%) affects the stability of the theophylline tablets with Prosolv® SMCC. Prosolv® SMCC had no effect on API stability as confirmed by the differential scanning calorimetry (DSC). Changes in peak placements were observed just after tabletting process, which might indicate that compression accelerated the incompatibilities between theophylline and Starch 1500. TGA analysis showed loss in tablets mass equal to water content in starch. GC-MS study established no chemical decomposition of theophylline. We demonstrated that high content of Starch 1500® (49%) in the tablet mass, affects stability on tablets containing theophylline and Prosolv® SMCC.
Assuntos
Celulose/química , Amido/química , Teofilina/química , Estabilidade de Medicamentos , Cromatografia Gasosa-Espectrometria de Massas , Dióxido de Silício/química , ComprimidosRESUMO
Severe skin diseases and systemic fungaemia are caused by Malassezia pachydermatis and Candida albicans respectively. Antifungal therapies are less effective because of chronic character of infections and high percentage of relapses. Therefore, there is a great need to develop new strategies of antifungal therapies. We previously found that oxythiamine decreases proliferation of yeast (Saccharomyces cerevisiae), therefore we suggest that thiamine antivitamins can be considered as antifungal agents. The aim of this study was the comparison of thiamine antivitamins (oxythiamine, amprolium, thiochrome, tetrahydrothiamine and tetrahydrooxythiamine) inhibitory effect on the growth rate and energetic metabolism efficiency in non-pathogenic S. cerevisiae and two potentially pathogenic species M. pachydermatis and C. albicans. Investigated species were cultured on a Sabouraud medium supplemented with trace elements in the presence (40 mg l(-1)) or absence of each tested antivitamins to estimate their influence on growth rate, enzyme activity and kinetic parameters of pyruvate decarboxylase and malate dehydrogenase of each tested species. Oxythiamine was the only antivitamin with antifungal potential. M. pachydermatis and S. cerevisiae were the most sensitive, whereas C. albicans was the least sensitive to oxythiamine action. Oxythiamine can be considered as supportive agent in superficial mycoses treatment, especially those caused by species from the genus Malassezia.
Assuntos
Antifúngicos/farmacologia , Antimetabólitos/farmacologia , Candida albicans/efeitos dos fármacos , Candidíase Cutânea/tratamento farmacológico , Dermatomicoses/tratamento farmacológico , Malassezia/efeitos dos fármacos , Tiamina/antagonistas & inibidores , Antifúngicos/uso terapêutico , Antimetabólitos/uso terapêutico , Candida albicans/crescimento & desenvolvimento , Candidíase Cutânea/microbiologia , Dermatomicoses/microbiologia , Fungemia/tratamento farmacológico , Fungemia/microbiologia , Humanos , Malassezia/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Oxitiamina/farmacologia , Oxitiamina/uso terapêutico , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/crescimento & desenvolvimentoRESUMO
Malassezia pachydermatis can cause infections of the skin and mucous membranes, especially in animals. It becomes a problem also in medicine. It is considered that metabolic disorders as well as hormonal and immunological status of the host promote diseases caused by M. pachydermatis. Here we consider whether specific features of fungi could also favour infections. We checked whether there are differences in lipid profiles between strains obtained from dogs with otitis externa and strains obtained from healthy dogs. Lipid profiles were determined using thin layer chromatography and gas chromatography-mass spectrometry. All analyses were carried out on 32 strains derived from dogs with otitis externa and 31 strains isolated from dogs without symptoms of disease. The results show that strains isolated from dogs without symptoms of otitis externa are characterised by a higher content of fatty acids. They contain significantly more behenic and lignoceric acids on medium without addition of lipids, and more oleic acid and total monounsaturated fatty acids on medium with lipids supplementation. These strains have also a higher content of esters of ergosterol and triglycerides. Data obtained show differences which may be specific features of M. pachydermatis-specific strains related to the ability of infection, which could be not directly related of the host condition.
Assuntos
Dermatomicoses/veterinária , Doenças do Cão/microbiologia , Lipídeos/análise , Malassezia/química , Malassezia/isolamento & purificação , Otite Externa/veterinária , Animais , Dermatomicoses/microbiologia , Cães , Ácidos Graxos/análise , Otite Externa/microbiologiaRESUMO
Proline dehydrogenase/proline oxidase (PRODH/POX) is an enzyme catalyzing the first step of proline degradation, during which ROS and/or ATP is generated. POX is widely distributed in living organisms and is responsible for a number of regulatory processes such as redox homeostasis, osmotic adaptation, cell signaling and oxidative stress. Recent data provided evidence that POX plays an important role in carcinogenesis and tumor growth. POX may induce apoptosis in both intrinsic and extrinsic way. Due to ROS generation, POX may induce caspase-9 activity, which mediates mitochondrial apoptosis (intrinsic apoptosis pathway). POX can also stimulate TRAIL (tumor necrosis factorrelated apoptosis inducing ligand) and DR5 (death receptor 5) expression, resulting in cleavage of procaspase-8 and thus extrinsic apoptotic pathway. However, this tumor suppressor in certain environmental conditions may act as a prosurvival factor. Genotoxic, inflammatory and metabolic stress may switch POX from tumor growth inhibiting to tumor growth supporting factor. The potential mechanisms which may regulate switching of POX mode are discussed in this review.
Assuntos
Neoplasias/enzimologia , Prolina Oxidase/metabolismo , Prolina/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Apoptose/fisiologia , Humanos , Terapia de Alvo Molecular , Neoplasias/patologia , Neoplasias/terapia , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/fisiologiaRESUMO
Cryptorchidism is the most common congenital birth defect in boys and affects about 2-4% full-term male neonates. Its etiology is multifactorial. Purpose. To evaluate the serum bisphenol A (BPA) levels in boys with cryptorchidism and healthy boys and to assess the risk of environmental exposure to BPA using the authors' questionnaire. The data were acquired from a study on boys with cryptorchidism (n = 98) and a control group (n = 57). Prior to surgery, all patients had BPA serum levels evaluated. The size, position, rigidity of the testis, and abnormality of the epididymis of the undescended testis were assessed. Parents also completed a questionnaire on the risks of exposure to BPA in everyday life. Results. The testes in both groups were similar in size. The turgor of the undescended testis in the group of boys with cryptorchidism was decreased. Free serum BPA level in cryptorchid boys and in the control group was not statistically significant (p > 0.05). The conjugated serum BPA level in cryptorchid boys and in the control group was statistically significant (p ≤ 0.05). Total serum BPA level in cryptorchid boys and in the control group was statistically significant (p < 0.05). Serum total BPA level was related with a positive answer about problems with conception (p < 0.02). Conclusion. Our study indicated that high serum BPA was associated with cryptorchidism.
RESUMO
Propolis is a resin that is collected by honeybees from various plant sources. Due to its pharmacological properties, it is used in commercial production of nutritional supplements in pharmaceutical industry. In this study, gas chromatography-mass spectrometry was applied for quality control analysis of the three commercial specimens containing aqueous-alcoholic extracts of bee propolis. More than 230 constituents were detected in analyzed products, including flavonoids, chalcones, cinnamic acids and their esters, phenylpropenoid glycerides, and phenylpropenoid sesquiterpenoids. An allergenic benzyl cinnamate ester was also identified in all tested samples. This analytical method allows to evaluate biological activity and potential allergenic components of bee glue simultaneously. Studies on chemical composition of propolis samples may provide new approach to quality and safety control analysis in production of propolis supplementary specimens.
Assuntos
Própole/química , Animais , Abelhas , Cromatografia Gasosa-Espectrometria de Massas , Própole/economia , Controle de QualidadeRESUMO
Integrin receptors are considered to be the key factors in carcinogenesis. αIIbß3-Integrin (GP IIb/IIIa) is the main glycoprotein of the surface of platelets, its presence has also been noted on the certain cancer cell lines. The molecular mechanism of its action in cancer cells remains unknown. This study presents effects of two αIIbß3-inhibitors: Abciximab and Eptifibatide on apoptosis, expression of proline oxidase (POX), signaling molecules ERK 1/2, transcription factor NF-κB and HIF-1α, vascular endothelial growth factor (VEGF) as well as DNA biosynthesis, collagen biosynthesis and prolidase activity in MCF-7 breast cancer cells. Both ligands induced apoptosis, however we found significant differences in molecular mechanism of action between tested αIIbß3-inhibitors. These differences include expression of POX, HIF-1α, NF-κB,VEGF and collagen biosynthesis. Eptifibatide presented stronger proapoptotic activity in MCF-7 cells than Abciximab. Results of this study suggest that Eptifibatide may be considered as a novel candidate for development of new anticancer therapy.
Assuntos
Anticorpos Monoclonais/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Fragmentos Fab das Imunoglobulinas/farmacologia , Peptídeos/farmacologia , Abciximab , Antineoplásicos/farmacologia , Neoplasias da Mama/patologia , Eptifibatida , Feminino , Humanos , Ligantes , Células MCF-7 , Inibidores da Agregação Plaquetária/farmacologia , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidoresRESUMO
Differential scanning calorimetry (DSC) is an analytical procedure used to determine the differences in the heat flow generated or absorbed by the sample. This method allows to assess purity and polymorphic form of drug compounds, to detect interactions between ingredients of solid dosage forms and to analyze stability of solid formulations. The aim of this study was the assessment of compatibility between acetaminophen (API) and different types of excipients often used in tablets compression: polyvinylpyrrolidone, crospovidone, pregelatinized starch, microcrystalline cellulose and magnesium stearate by differential scanning calorimetry. The study contains results of thermal analysis of excipients and individually performed mixtures of these substances with acetaminophen before and after compression and after 6 months storage of tablets at different temperature and relative humidity conditions (25 +/- 2 degrees C /40 +/- 5% RH, 25 +/- 2 degrees C /60 +/- 5% RH, 40 +/- 2 degrees C /75 +/- 5% RH) for a period of 6 months. To detect possible changes of API chemical structure, gas chromatography-mass spectrometry (GC-MS) was also applied. GC-MS with electron impact ionization (EI) was employed to determine the fragmentation pattern of API. It was shown that the developed formulations showed excellent compatibility among all excipients used except Kollidon CL. The interaction with Kollidon CL is probably a result of a physical reaction as confirmed by GC-MS analyses. Obtained results revealed that DSC can be successfully applied to evaluate possible incompatibilities between acetaminophen and Kollidon.
Assuntos
Acetaminofen/química , Analgésicos não Narcóticos/química , Varredura Diferencial de Calorimetria , Química Farmacêutica , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Cromatografia Gasosa-Espectrometria de Massas , Umidade , Solubilidade , Espectrometria de Massas por Ionização por Electrospray , Comprimidos , TemperaturaRESUMO
Thyroid diseases are one of the most common metabolic disorders in the human population. In this work, we present data concerning changes in the activity and kinetic parameters of several enzymes associated with both anabolic (glucose-6-phosphate dehydrogenase-G6PDH, EC 1.1.1.49; 6-phosphogluconate dehydrogenase-6PGDH, EC 1.1.1.44; malic enzyme-ME, EC 1.1.1.40; and isocitrate dehydrogenase-IDH, EC 1.1.1.42) and catabolic (NAD-dependent malate dehydrogenase-NAD-MDH, EC 1.1.1.37; and lactate dehydrogenase-LDH, EC 1.1.1.27) processes under conditions of hypothyroidism and T3 treatment. Hypothyroidism was induced in rats by the surgical removal of the thyroid gland. T3-treated rats were injected by T3 (0.5 mg T3/kg body weight daily during 10 days). We have found that T3 treatment caused an increase of NAD-MDH activity as well as heart hypertrophy whereas the activity of LDH increased in the direction of pyruvate reduction. Moreover, we observed increased activity of both enzymes in the liver. These results confirm earlier observation concerning the relevance of oxidative metabolism in the heart under T3 treatment. Hypothyroidism resulted in changes in the LDH activity in the heart whereas NAD-MDH activity did not change. Moreover, our data show that T3 treatment caused an increase of G6PDH, 6PGDH, and ME activities in the liver. We also observed a decrease of IDH activity in both organs, whereas hypothyroidism caused the opposite effect. This data indicate that either deficiency or excess of thyroid hormones can prove to be particularly dangerous for the physiology of the heart muscle by disturbing bioenergetic and anabolic processes (AU)
Assuntos
Animais , Ratos , Hipotireoidismo/tratamento farmacológico , Tri-Iodotironina/farmacocinética , Fígado/enzimologia , Coração/fisiopatologia , Miocárdio/enzimologiaRESUMO
Thyroid diseases are one of the most common metabolic disorders in the human population. In this work, we present data concerning changes in the activity and kinetic parameters of several enzymes associated with both anabolic (glucose-6-phosphate dehydrogenase-G6PDH, EC 1.1.1.49; 6-phosphogluconate dehydrogenase-6PGDH, EC 1.1.1.44; malic enzyme-ME, EC 1.1.1.40; and isocitrate dehydrogenase-IDH, EC 1.1.1.42) and catabolic (NAD-dependent malate dehydrogenase-NAD-MDH, EC 1.1.1.37; and lactate dehydrogenase-LDH, EC 1.1.1.27) processes under conditions of hypothyroidism and T(3) treatment. Hypothyroidism was induced in rats by the surgical removal of the thyroid gland. T(3)-treated rats were injected by T(3) (0.5 mg T(3)/kg body weight daily during 10 days). We have found that T(3) treatment caused an increase of NAD-MDH activity as well as heart hypertrophy whereas the activity of LDH increased in the direction of pyruvate reduction. Moreover, we observed increased activity of both enzymes in the liver. These results confirm earlier observation concerning the relevance of oxidative metabolism in the heart under T(3) treatment. Hypothyroidism resulted in changes in the LDH activity in the heart whereas NAD-MDH activity did not change. Moreover, our data show that T(3) treatment caused an increase of G6PDH, 6PGDH, and ME activities in the liver. We also observed a decrease of IDH activity in both organs, whereas hypothyroidism caused the opposite effect. This data indicate that either deficiency or excess of thyroid hormones can prove to be particularly dangerous for the physiology of the heart muscle by disturbing bioenergetic and anabolic processes.
Assuntos
Hipotireoidismo/metabolismo , Fígado/enzimologia , Miocárdio/enzimologia , Tri-Iodotironina/metabolismo , Animais , Glucosefosfato Desidrogenase/metabolismo , Coração , Hipotireoidismo/enzimologia , Cinética , L-Lactato Desidrogenase/metabolismo , Fígado/metabolismo , Masculino , Miocárdio/metabolismo , Fosfogluconato Desidrogenase/metabolismo , Ratos , Ratos WistarRESUMO
Malassezia pachydermatis and Candida albicans are fungi involved in the skin diseases and systemic infections. The therapy of such infections is difficult due to relapses and problems with pathogen identification. In our study, we compare the fatty acids profile of M. pachydermatis, C. albicans and S. cerevisiae to identify diagnostic markers and to investigate the effect of oxythiamine (OT) on the lipid composition of these species. Total fatty acid content is threefold higher in C. albicans and M. pachydermatis compared with S. cerevisiae. These two species have also increased level of polyunsaturated fatty acids (PUFA) and decreased content of monounsaturated fatty acids (MUFA). We noted differences in the content of longer chain (>18) fatty acids between studied species (for example a lack of 20 : 1 in S. cerevisiae and 22 : 0 in M. pachydermatis and C. albicans). OT reduces total fatty acids content in M. pachydermatis by 50%. In S. cerevisiae, OT increased PUFA whereas it decreased MUFA content. In C. albicans, OT decreased PUFA and increased MUFA and SFA content. The results show that the MUFA to PUFA ratio and the fatty acid profile could be useful diagnostic tests to distinguish C. albicans, M. pachydermatis and S. cerevisiae, and OT affected the lipid metabolism of the investigated species, especially M. pachydermatis.