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1.
Cell Biochem Funct ; 30(3): 211-6, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22125185

RESUMO

Total parenteral nutrition (TPN) is essential for patients with postoperative impairing gastrointestinal function who are unable to receive and absorb oral/enteral feeding for at least 7 days. Oxidative stress plays a major role in the ethiopathogenesis of cancers. In this study, total antioxidant status (TAS), glutathione peroxidase (GPx), superoxide dismutase, malondialdehyde and ascorbic acid were studied in patients operated because of small intestine, colorectal or pancreatic cancer and subsequently receiving TPN in comparison with patients receiving standard nutrition after the operation. TAS level and GPx activity were decreased in patients with small intestine cancer but did not differ in patients with colorectal and pancreatic cancer before and after surgery. In all patient groups receiving TPN, superoxide dismutase activity after the surgery was kept at the same level as before. On the fifth day after the surgery, malondialdehyde concentration in each group was restored to the value observed before surgery. On the fifth day of TPN treatment, ascorbic acid concentration was increased in every group of patients. TPN applied during the postoperative period alleviates oxidative stress resulting from surgery. In the case of small intestine cancer, the addition of vitamins and antioxidants to the nutrition mixture seems to result in depletion of antioxidant enzymes' activities.


Assuntos
Antioxidantes/metabolismo , Neoplasias Gastrointestinais/terapia , Nutrição Parenteral Total , Idoso , Ácido Ascórbico/metabolismo , Procedimentos Cirúrgicos do Sistema Digestório , Feminino , Neoplasias Gastrointestinais/metabolismo , Neoplasias Gastrointestinais/cirurgia , Glutationa Peroxidase/metabolismo , Humanos , Masculino , Malondialdeído/metabolismo , Pessoa de Meia-Idade , Estresse Oxidativo , Cuidados Pós-Operatórios , Superóxido Dismutase/metabolismo
2.
J Cardiothorac Vasc Anesth ; 26(3): 395-402, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22206712

RESUMO

OBJECTIVES: Neuropsychological disorders are some of the most common complications of coronary artery bypass graft (CABG) surgery. The early diagnosis of postoperative brain damage is difficult and mainly based on the observation of specific brain injury markers. The aim of this study was to analyze the effects of volatile anesthesia (VA) on plasma total and ionized arteriovenous magnesium concentrations in the brain circulation (a-vtMg and a-viMg), plasma matrix metalloproteinase-9 (MMP-9), and glial fibrillary acidic protein (GFAP) in adult patients undergoing CABG surgery. DESIGN: An observational study. SETTING: The Department of Cardiac Surgery in a Medical University Hospital. PATIENTS AND METHODS: Studied parameters were measured during surgery and in the early postoperative period. Patients were assigned to 3 groups: group O, patients who did not receive VA; group ISO, patients who received isoflurane; and group SEV, patients who received sevoflurane. RESULTS: Ninety-two patients were examined. CABG surgery increased MMP-9 and GFAP. The highest MMP-9, GFAP, and the most dramatic disorders in a-vtMg and a-viMg were noted in group O. CONCLUSIONS: Cardiac surgery increased plasma MMP-9 and GFAP concentrations. Changes in MMP-9, GFAP, and arteriovenous tMg and iMg were significantly higher in group O. Volatile anesthetics, such as ISO or SEV, reduced plasma MMP-9, GFAP concentrations, and disturbances in a-vtMg and a-viMg.


Assuntos
Anestésicos Inalatórios/uso terapêutico , Lesões Encefálicas/prevenção & controle , Ponte de Artéria Coronária/efeitos adversos , Magnésio/sangue , Fármacos Neuroprotetores/uso terapêutico , Idoso , Biomarcadores/sangue , Encéfalo/metabolismo , Lesões Encefálicas/diagnóstico , Lesões Encefálicas/etiologia , Feminino , Proteína Glial Fibrilar Ácida/sangue , Humanos , Isoflurano/uso terapêutico , Masculino , Metaloproteinase 9 da Matriz/sangue , Éteres Metílicos/uso terapêutico , Pessoa de Meia-Idade , Sevoflurano
3.
Bioorg Med Chem ; 19(17): 5103-16, 2011 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-21839643

RESUMO

Eleven novel 3-(2-furanyl)-8-aryl-7,8-dihydroimidazo[2,1-c][1,2,4]triazin-4(6H)-ones (12-22) were designed and obtained from appropriate 1-aryl-2-hydrazonoimidazolidines (1-11) by condensation reaction with 2-oxo-2-furanacetic acid and subsequent cyclocondensation of intermediate chain derivatives. IR, (1)H NMR and (13)C NMR spectra and elemental analyses confirmed the chemical structure of all the synthesized compounds. The reversed-phase HPLC method was optimized and proved to be applicable and reliable for the analysis of these unknown small molecules (12-22). These compounds were chromatographed on octadecyl silica (ODS) stationary phase and their hydrophobic parameters expressed as the log k(w) values were determined by RP-HPLC, using mixtures of methanol and water as mobile phases with different methanol concentrations. Octane-1-sulfonic acid sodium salt (OSA-Na) and 20% acetate buffer (pH 3.5) was added to the mobile phase (eluent containing 0.01 M/L OSA-Na in organic modifier (MeOH)-buffered mobile phase). The high values of regression coefficients (r >0.9841) for all the compounds investigated proved the excellent fit between experimental data and the Snyder-Soczewinski equation. Results obtained from the reversed-phase HPLC were compared both with those theoretically calculated and with those obtained from an ALOGPS 2.1. software by the use of nine different computational methods for estimation of log P. The predicted values of log P by use of AB log P algorithm revealed the best correlation with the experimental log k(w) values for the investigated solutes, since a good correlation (r=0.7760) between these quantities was found. The majority of novel imidazotriazinones were found to be evidently effective in vitro against human cancerous cells (HeLa and T47D) in an effective concentration of 50 µg/mL. Five compounds (13, 15, 16, 18 and 22) revealed remarkable antiproliferative activities and selective cytotoxicities for cancer cells over normal HSF cells. Therefore these ones may be considered as a basis for the design of novel useful non-toxic (13, 15 and 16) and low toxic (18 and 22) anticancer agents.


Assuntos
Antineoplásicos/síntese química , Fibroblastos/efeitos dos fármacos , Imidazóis/química , Triazinas/química , Antineoplásicos/química , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Cromatografia de Fase Reversa , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Interações Hidrofóbicas e Hidrofílicas , Espectroscopia de Ressonância Magnética , Conformação Molecular , Triazinas/síntese química , Triazinas/toxicidade
4.
Magnes Res ; 23(4): 169-79, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21169130

RESUMO

BACKGROUND: Changes in plasma matrix metalloproteinase 9 (MMP-9) concentrations and parallel changes in brain magnesium homeostasis have not been examined in cardiac surgery patients. The purpose of the present study was to analyse these relationships in patients undergoing coronary artery bypass surgery (CABG) with extracorporeal circulation (ECC). Additionally, the effect of volatile anaesthetics was considered. PATIENTS AND METHODS: Adult patients undergoing CABG with ECC under general anaesthesia were studied. Plasma MMP-9 and total (tMg) and ionized (iMg) magnesium concentrations were measured during surgery and during the early postoperative period. The plasma arteriovenous (a-v) tMg and iMg differences in the brain circulation were considered to be markers for brain magnesium homeostasis. The Mini-Mental State Examination test and computer tomography were used to diagnose postoperative neuropsychological disorders (PNPDs). RESULTS: In total, 92 patients were examined. PNPDs were noted in 17 cases. Cardiac surgery resulted in increased plasma levels of MMP-9. The highest MMP-9 concentrations were observed in patients with PNPDs. MMP-9 concentrations strongly correlated with a-v tMg and a-v iMg differences. Compared with arterial measurements, venous tMg and iMg concentrations were higher during and immediately after surgery and lower during the early postoperative period. The most severe differences in a-v tMg and iMg were noted in patients with PNPDs. CONCLUSION: 1. Cardiac surgery resulted in an increase in plasma MMP-9 concentrations. 2. This increase in MMP-9 was significantly greater in patients with PNPDs. 3. The plasma MMP-9 concentration was correlated with disorders of brain Mg homeostasis.


Assuntos
Encéfalo/metabolismo , Ponte de Artéria Coronária , Magnésio/metabolismo , Metaloproteinase 9 da Matriz/sangue , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
5.
Pharmacol Rep ; 61(5): 885-91, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19904012

RESUMO

The aim of this work was to evaluate the possibility of using of the new selenoorganic ring compound, 3-(o-chlorobenzoylamino)-2-(o-tolylimino)-4-methyl-4-selenazoline, as a selenium supplement by investigating the influence of its short-term administration on Se accumulation and antioxidant status in kidney. For 10 days, adolescent male Wistar rats were treated with saline (control group), Na(2)SeO(3) (Se-IN group) or the studied compound (Se-ORG group) (5 x 10(-4) mg Se/g of once a day) via a stomach tube. The selenium concentration, total antioxidant status (TAS), activities of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), concentrations of ascorbic acid (AA) and reduced glutathione (GSH) and concentration of malonyldialdehyde (MDA) were determined in the kidney homogenates. TAS was significantly reduced in the Se-ORG group compared to the control. Reduced glutathione was markedly decreased in Se-treated animals compared to the control and in the Se-ORG group compared to the Se-IN group. Malonyldialdehyde was significantly increased in the Se-supplemented groups compared to the control group but considerably less so in the Se-ORG group. All other studied parameters displayed no significant differences. No increase in the accumulation of selenium and the partial impairment of the antioxidant status and enhancement of lipid peroxidation in the kidneys resulting from Se treatment could suggest that in the first period of administration, excess selenium was excreted with urine, leading to a disturbance of kidney functions. Comparison of the effect of our compound with that exerted by inorganic Na(2)SeO(3) suggests that the studied compound could be considered as a possible supplement after further investigations, including determination of selenium excretion with urine, as well as repetition of this study using a wide range of doses and periods of supplementation.


Assuntos
Antioxidantes/metabolismo , Rim/efeitos dos fármacos , Compostos Organosselênicos/farmacologia , Selenito de Sódio/farmacologia , Animais , Ácido Ascórbico/metabolismo , Suplementos Nutricionais , Glutationa/efeitos dos fármacos , Glutationa/metabolismo , Rim/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Ratos , Ratos Wistar , Selênio/metabolismo
6.
Bioorg Med Chem Lett ; 19(17): 5095-100, 2009 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-19631534

RESUMO

Molecular structure of 3,8-disubstituted 7,8-dihydroimidazo[2,1-c][1,2,4]triazin-4(6H)-ones (8-14) was confirmed by X-ray crystallography of 14. All the compounds were evaluated for their antitumour and antimetastatic activities in vitro. Furthermore, their cytotoxicities towards human normal cell line-HSF cells were established, allowing us to point out some structure-activity relationships. Among them, imidazotriazinone 12, revealing remarkable dose-dependent viability decreases in human myeloma RPMI 8226 cells, was found to be completely non-toxic towards normal HSF cells. In addition, heterobicycles 8-12 were proved to exhibit significant antimetastatic potentials in the motility assay.


Assuntos
Antineoplásicos/química , Triazinas/química , Antineoplásicos/síntese química , Antineoplásicos/toxicidade , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Conformação Molecular , Metástase Neoplásica , Relação Estrutura-Atividade , Triazinas/síntese química , Triazinas/toxicidade
7.
Magnes Res ; 21(4): 205-17, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19271418

RESUMO

UNLABELLED: The purpose of the study was to analyse the effects of different forms of magnesium supplementation on its serum concentrations and the frequency of atrial fibrillation in patients undergoing coronary artery bypass graft surgery with extracorporeal circulation (ECC). One hundred and twenty adult patients were examined. All of them received intravenous infusions of MgSO4 during surgery and the early postoperative period (18 hours). Moreover, some of them received preoperative Mg supplementation. Therefore, patients were divided into six groups: A) patients, receiving an intravenous infusion 3.33 mg of MgSO4 per min; B) those receiving preoperative, oral Mg supplementation (OPS-Mg) and intravenous 3.33 mg of MgSO4 per min; C) patients receiving intravenous 6.66 mg of MgSO4 per min; D) patients receiving OPS-Mg and 6.66 mg of MgSO4 per min; E) patients receiving intravenous 10 mg of MgSO4 per min; F) those receiving OPS-Mg and 10 mg of MgSO4 per min. Additionally, all patients were divided into three groups: O (patients, who did not receive dopamine or dobutamine infusions), DOP (those receiving dopamine infusions in doses dependent on their clinical state) and DOB (those receiving dobutamine infusions in doses dependent on their clinical state). Total serum Mg concentrations (Mg(t)) were measured at five points: 1) 10 min before anaesthesia; 2) 10 min after ECC; 3) 10 min after surgery, 4) in the morning of postoperative day 1, 5) in the morning of postoperative day 2. The data were analyzed statistically; values at the first measurement points were considered as baseline. In group A, Mg(t) decreased at time points 2, 3, 4. Similar changes were observed in group B, however, in both groups Mg(t) returned to the baseline value at time point 5. In groups C and D, Mg(t) decreased at point 2 and 3, whereas in groups E and F it was increased during all the study period. The changes in Mg(t) were slightly less in patients receiving OPS-Mg, these patients had a significantly higher Mg(t) at time point 1. Mg(t) decreased in the O, DOP and DOB groups at measurement points 2 and 3. Moreover, the lowest Mg(t) was observed in the DOP group. Atrial fibrillation (AF) was noted in 33 patients (27.5%). The highest percentage of patients with AF during the early postoperative days was observed in groups A and B (45%). In groups C, D, E and F, AF was detected in 25%, 20%, 20% and 10% of patients, respectively. The incidence of AF was significantly higher in groups A and B compared to the other groups. Moreover, episodes of AF were rarer in patients receiving preoperative, oral Mg supplementation. CONCLUSIONS: 1) ECC resulted in a decrease in Mg(t); 2) Mg infusion at the dose of 3.33 mg/min had little effect for the prevention of postoperative AF; 3) the infusion of 10 mg/min of MgSO4 maintained the level of Mg(t) during CABG and most effectively reduced AF; 4) OPS-Mg played a beneficial role in Mg(t) disturbances during CABG; 5) dopamine caused the most severe disturbances in serum Mg(t) concentration.


Assuntos
Fibrilação Atrial/prevenção & controle , Ponte Cardiopulmonar , Magnésio , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Infusões Intravenosas , Magnésio/administração & dosagem , Magnésio/sangue , Magnésio/uso terapêutico , Masculino , Pessoa de Meia-Idade
8.
Eur J Med Chem ; 43(2): 404-19, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17531354

RESUMO

3-Unsubstituted and 3-substituted-7-aryl-5H-6,7-dihydroimidazo[2,1-c][1,2,4]triazoles (1-14) were designed and obtained from biologically active 1-aryl-2-hydrazonoimidazolidines by cyclocondensation reaction with triethyl orthoformates (1-4), phenoxyacetic acid derivatives (5-13) and carbon disulfide (14), respectively. Their chemical structures were confirmed by IR, (1)H NMR, (13)C NMR, MS spectra and elemental analysis. In the high performance liquid chromatographic series of experiments, fourteen synthesized compounds (1-14) were chromatographed on octadecyl silica adsorbent and their lipophilicity parameter (logk(W)) was determined using various aqueous systems: mixture of water and organic modifiers (methanol - MeOH, acetonitrile - MeCN or dioxane - DX). Compounds 7 and 12 were evaluated for their cytotoxic activity against three cancer cell lines: human Caucasian colon adenocarcinoma cell line - LS180 (ECACC 87021202), human uterus carcinoma cell line - SiHa (ECACC 85060701) and human breast carcinoma cell line - T47D (ECACC 85102201). Compound 12 was found to be the most effective in vitro against human colon adenocarcinoma cell line (LS180). Moreover, the distinctly marked lower cytotoxicity of compounds 7 and 12 against the normal cell line - human skin fibroblasts (HSF) and almost several-fold higher against the examined cancer cell lines was ascertained. The cytotoxic effect of imidazotriazole 7 was noticed on DNA structure of breast cancer cell line (T47D) by using the comet assay. Compound 7 in concentration of 29.3 microM was found to possess efficiency for DNA strand breakage. In particular, this led to cutting of the DNA strands and formation of small fragments of DNA - two higher and one lighter in comparison with control DNA. Moreover, significant viability decreases in the human leukaemic RPMI 8226 cells treated with different concentrations of imidazotriazoles 8-12 were observed, suggesting their antiproliferative properties. Besides, three tested compounds (9, 13, 14) revealed significant antimicrobial activities with MIC values in the range of 30.9-44.0 microM. Compound 13 showed superior antibacterial activity to ampicillin and chloramphenicol in vitro, whereas 14 displayed superior antifungal activity to miconazole.


Assuntos
Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Lipídeos/química , Triazóis/síntese química , Triazóis/farmacologia , Anti-Infecciosos/química , Antineoplásicos/química , Linhagem Celular Tumoral , Dano ao DNA , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Testes de Sensibilidade Microbiana , Espectrofotometria Infravermelho , Triazóis/química
9.
Biometals ; 21(1): 53-9, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17447120

RESUMO

Lithium salts are widely used in psychiatry, but their presence in organism can result in both beneficial and adverse effects. Silicon, the third most abundant trace element in humans as well as antioxidant enzyme glutathione peroxidase (GPx) play important roles in organism. The disturbance of their level can cause severe disorders. The aim of our work was to evaluate the influence of Li2CO3 administration in drinking water for a period of 4 weeks on Si content and GPx activity in the tissues of liver, kidney, brain and femoral muscle in rats. The concentrations of provided solutions were 0.7, 1.4, 2.6, 3.6, 7.1 and 10.7 mmol Li+ x dm-3. GPx activity was decreased versus control as a consequence of Li treatment, particularly in kidney and brain. This effect could be suggested to contribute to renal abnormalities which could occur during Li therapy. Si tissue level was significantly enhanced versus control in liver and femoral muscle in groups receiving high Li doses. In brain no well-marked changes were observed, whereas in kidney we observed the depletion in low-Li-groups, restoration of Si level in higher-Li-groups and unexpected decrease in the highest-Li-group. Positive correlations between Si content and GPx activity in the tissues of kidney (r = 0.677) and brain (r = 0.790) as well as negative correlation (r = -0.819) in femoral muscle were found. We consider that our results give some reason for suggesting that monitoring of silicon level in patients undergoing Li therapy could be recommended. However, more investigations should be performed, particularly regarding the relationships between Si and GPx in blood and urine Si excretion during lithium administration.


Assuntos
Glutationa Peroxidase/metabolismo , Compostos de Lítio/farmacologia , Silício/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Ingestão de Líquidos , Rim/efeitos dos fármacos , Rim/metabolismo , Carbonato de Lítio/administração & dosagem , Carbonato de Lítio/farmacologia , Compostos de Lítio/administração & dosagem , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Músculos/efeitos dos fármacos , Músculos/metabolismo , Ratos , Ratos Wistar
10.
Eur J Med Chem ; 43(5): 1085-94, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-17868955

RESUMO

Synthesis, structure elucidation and anticancer activities of novel fused 1,2,4-triazine aryl derivatives containing the ethoxycarbonyl (6-10) and carbohydrazide formations (11-15) are presented. Molecular structures of the synthesized compounds were confirmed by IR, (1)H NMR, (13)C NMR, EI-MS spectra and elemental analyses. Antitumour activities in vitro for heterobicyclic hydrazides of the type 11-14 were evaluated by BrdU method for human LS180, SiHa and T47D carcinoma cells. Amongst them, hydrazide 14 has exhibited remarkable inhibitory effect against SiHa and LS180 tumour cells, and simultaneously was found to be non-toxic towards the human normal cell line-HSF cells. Furthermore, the pulse field gel electrophoresis experiment was performed for characterizing DNA-cleaving activity of heterobicycle 14. The DNA fragments of 2500, 2000 and 500 kilobase pairs (kbp) were commonly detected in the cancer cell lines (SiHa, LS180 and T47D) treated with compound 14. DNA fragmentation pattern, since three types of fragments induced by the tested hydrazide of the type 14 were detected, suggesting a way of interaction with DNA. It is worth pointing out, that DNA strand breaks were also produced in human breast cancer (T47D) cells, a cell line where the induction of DNA fragmentation is very difficult. Moreover, the statistically significant apoptotic activity in T47D human breast cancer cells for the tested heterobicycle 14 was proved using the annexin V-binding assay. The antiproliferative properties in vitro for compounds 6-14 were evaluated by MTT method for human leukaemic Jurkat cells. Significant viability decreases in Jurkat cells treated with different concentrations of compounds 10 and 11 were observed, suggesting that these derivatives have antiproliferative activities. Their acute toxicities were established. For these compounds the influence on the central nervous system of mice in behavioural tests was examined. Molecular structure for free base of the intermediate 4 was confirmed by (1)H-(1)H COSY, HMBC and HMQC correlations.


Assuntos
Antineoplásicos/síntese química , Compostos Heterocíclicos com 2 Anéis/síntese química , Hidrazinas/síntese química , Imidazóis/síntese química , Triazinas/síntese química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose , Comportamento Animal/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quebras de DNA , Ensaios de Seleção de Medicamentos Antitumorais , Compostos Heterocíclicos com 2 Anéis/química , Compostos Heterocíclicos com 2 Anéis/farmacologia , Humanos , Hidrazinas/química , Hidrazinas/farmacologia , Imidazóis/química , Imidazóis/farmacologia , Masculino , Camundongos , Relação Estrutura-Atividade , Testes de Toxicidade Aguda , Triazinas/química , Triazinas/farmacologia
11.
Pharmacol Rep ; 59(3): 291-5, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17652829

RESUMO

The aim of this work was to determine the influence of different doses of lithium on magnesium concentration in plasma and tissues of rats. For a period of eight weeks rats had been provided with aqueous solutions of Li(2)CO(3) whose concentrations were established as follows: 0.7; 1.4; 2.6; 3.6; 7.1; 10.7 mmol Li(+)/l. Magnesium concentration was determined in plasma and tissue supernatants. Lithium caused no changes in magnesium concentration in plasma, whereas Mg concentration in tissues was found to be enhanced, although the degree of the increment depended on the studied tissue. In the liver, brain and heart muscle, the increase was statistically insignificant vs. control. In the kidney, the higher Li doses were required to result in the significant Mg enhancement, whereas in femoral muscle all the used doses caused well-marked Mg increase vs. control. Positive correlations between average daily Li intake and tissue Mg concentration in the kidney (r = 0.650) and femoral muscle (r = 0.696) were found. In conclusion, the present study indicates that the different Li doses disturbed tissue homeostasis of magnesium. The increase in Mg tissue concentration, observed in groups receiving higher Li doses can influence nervous-muscular excitability.


Assuntos
Carbonato de Lítio/farmacologia , Magnésio/metabolismo , Administração Oral , Animais , Relação Dose-Resposta a Droga , Carbonato de Lítio/administração & dosagem , Masculino , Ratos , Ratos Wistar
12.
Bioorg Med Chem ; 15(16): 5480-6, 2007 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-17572093

RESUMO

The in vitro biological activities of novel derivatives of methyl and ethyl 2-(4-oxo-8-aryl-2H-3,4,6,7-tetrahydroimidazo[2,1-c][1,2,4]triazin-3-yl)acetates (3a, 3d-j) have been evaluated and are reported. The final heterobicycles (3a-j) were obtained from monocyclic 1-aryl-2-hydrazonoimidazolidines (2a-f) by addition and cyclization reaction with fumaric acid esters. In particular, compounds 3d and 3e were found to exhibit comparable antibacterial potencies in vitro as that of ampicillin. Heterobicycles of the 3e, 3g and 3j type were screened for their antiviral activities against the selected viruses' DNA (human adenovirus type 5-Ad-5) and RNA (human enterovirus-Echo-9). Simultaneously, their cytotoxicities towards HEK-293 and GMK cells were established. In particular, heterobicycle 3j, completely non-toxic for GMK cells, was found to exhibit virucidal properties against Echo-9 virus justifying its further investigation as the potential antiviral agent.


Assuntos
Antibacterianos/síntese química , Antibacterianos/toxicidade , Antivirais/síntese química , Antivirais/toxicidade , Ésteres/síntese química , Ésteres/toxicidade , Triazinas/química , Antibacterianos/química , Antivirais/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ésteres/química , Compostos Heterocíclicos/síntese química , Compostos Heterocíclicos/química , Compostos Heterocíclicos/toxicidade , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
13.
Bioorg Med Chem ; 15(8): 2837-49, 2007 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-17331732

RESUMO

The series of 8-aryl-2,6,7,8-tetrahydroimidazo[2,1-c][1,2,4]triazine-3,4-diones (11-20) and 8-aryl-4-imino-2,3,7,8-tetrahydroimidazo[2,1-c][1,2,4]triazin-3(6H)-ones (21-25) were designed and their in vitro cytotoxic activities against human LS180, HeLa, T47D, A549 and RPMI 8226 carcinoma cells are presented. In the crystalline state molecule 12 exists as the predominant tautomeric 3-oxo form, whereas the second possible 3-hydroxy tautomer is not observed. Compound 19 revealed a strong affection to LS180 cancer cells at lower tested concentration (37.9 microM) and simultaneously was found to be non-toxic towards the normal cell line investigated--GMK cells. Furthermore, this compound was proved to possess the efficiency for DNA strand breakage of the examined cancer cell lines. However, imidazotriazin-3,4-dione 20 was able to cause significant viability decreases in human RPMI 8226 peripheral blood myeloma cells. Compound 22 has exhibited remarkable inhibitory effects against LS180 and A549 carcinoma cells, whereas 24 revealed the highest growth inhibition against A549 cell line. Simultaneously, at lower tested concentration these compounds were proved to be completely non-toxic for GMK cells. Moreover, cytotoxic and antibacterial properties of starting, tautomeric 1-aryl-2-hydrazonoimidazolidines (1-6 and 8-9) are presented. Six of them (1-2, 4-6 and 9) proved active as antimicrobials. All these compounds revealed MIC values in the range of 15.0-78.6 microM. Their activities were compared to those of ampicillin and chloramphenicol.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Imidazóis/síntese química , Imidazóis/farmacologia , Triazinas/síntese química , Triazinas/farmacologia , Ampicilina/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Linhagem Celular Tumoral , Fenômenos Químicos , Físico-Química , Cloranfenicol/farmacologia , Chlorocebus aethiops , Cristalografia por Raios X , Dano ao DNA , DNA de Neoplasias/química , DNA de Neoplasias/efeitos dos fármacos , Células HeLa , Humanos , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Testes de Sensibilidade Microbiana , Modelos Moleculares , Conformação Molecular , Estereoisomerismo , Relação Estrutura-Atividade
14.
Bone ; 39(1): 100-5, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16469550

RESUMO

Skeletal disorders in rapidly growing poultry are commonplace. This study was performed to investigate the effect of ornithine alpha-ketoglutarate (OKG) administration during the last 7 weeks of life on structural properties, mineralization, and mechanical endurance of skeleton in turkeys at slaughter. Healthy HB Medium Bronze female turkeys were randomly assigned to two weight-matched groups at the age of 12 weeks. OKG was administered orally to the experimental group (N=17) at the dose of 0.4 g/kg body weight per day, while the control group (N=16) received an equal dose of the vehicle. The turkeys were slaughtered at the age of 19 weeks and the tibiae were isolated for analysis. The effect of OKG on skeletal system development in turkeys was evaluated in relation to both geometrical and mechanical properties as well as quantitative computed tomography (QCT). Free amino acids concentrations were assessed with the use of ion-exchange chromatography. Significantly increased bone mineral density of the trabecular and the cortical bone of tibia in the turkeys given OKG for the last 7 weeks of production cycle were observed (P<0.05). OKG administration improved mechanical endurance of the tibia estimated by the three-point bending test (P<0.01). Plasma amino acid analyses showed increased level of aspartate, proline, alanine, valine, isoleucine, leucine, and ornithine (all P<0.05) after OKG treatment, whereas cystathionine concentration was decreased (P=0.03). Obtained results indicate that oral OKG administration has beneficial effects on skeletal development in fast growing turkeys and this effect is connected with increased amino acid synthesis. These observations may serve to improve skeletal properties in birds, especially when considering that skeletal disorders often affect the tibia and the proper function of the skeletal system plays an essential role in animal welfare and poultry production.


Assuntos
Densidade Óssea/efeitos dos fármacos , Ornitina/análogos & derivados , Tíbia/efeitos dos fármacos , Perus/metabolismo , Aminoácidos/sangue , Animais , Fenômenos Biomecânicos , Feminino , Ornitina/administração & dosagem , Ornitina/metabolismo , Ornitina/farmacologia , Distribuição Aleatória , Perus/sangue
15.
Bioorg Med Chem ; 14(11): 3635-42, 2006 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-16455261

RESUMO

1-Arylimidazolidine-2-thiones (1a-g) were synthesized by the condensation reaction of N-arylethylenediamines with carbon disulfide in xylene medium. Their further alkylation with methyl iodide led to the formation of some biologically active 1-aryl-2-methylthio-imidazolines (2a-g). The 7-(4-methylphenyl)-3-methylthio-5H-6,7-dihydroimidazo[2,1-c][1,2,4]triazole (4b) was obtained by the alkylation of the respective 7-(4-methylphenyl)-2,5,6,7-tetrahydroimidazo[2,1-c][1,2,4]triazol-3(H)-thione (3b) with methyl iodide. Antimicrobial activities of 1-aryl-2-methylthio-imidazolines (2a-g) and the 7-(4-methylphenyl)-3- methylthio-5H-6,7-dihydroimidazo[2,1-c][1,2,4]triazole (4b) are presented. All tested compounds showed MIC in the range of 11.0-89.2 microM. Compounds 2a,e were found to be equipotent to chloramphenicol in vitro, whereas 2a,c,e-g and 4b showed superior activity (MIC) to ampicillin.


Assuntos
Antibacterianos/síntese química , Imidazóis/síntese química , Imidazóis/farmacologia , Imidazolinas/síntese química , Compostos de Sulfidrila/química , Triazóis/síntese química , Triazóis/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Imidazolinas/química , Imidazolinas/farmacologia , Técnicas In Vitro , Testes de Sensibilidade Microbiana , Estrutura Molecular
16.
Magnes Res ; 17(2): 72-8, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15319137

RESUMO

Experiment was carried on Wistar male rats. Eleven groups, each of 6 rats, were given: group I: plumbum nitrate (500 mg Pb/dm3), group II: plumbum ions--500 mg Pb/dm3 and quercetin--200 mg/dm3, group III the same what group II and glutamine 4 g/dm3, group IV: Pb(NO3)2--500 mg Pb/dm3 and catechin (200 mg/dm3), and group V the same as group IV, Pb ions, catechin, and additionally glutamine--4 g/dm3. The IA - VA groups obtained the same that groups I-V but they received instead of lead cadmium chloride in amount of 500 mg Cd/dm3. Group IX was a control group, and that animals received redistilled water to drink. After six weeks of experiment blood, liver and kidneys were collected, and magnesium and branched amino acids concentrations were determined. The aim of these studies was to determine the influence of administered quercetin and catechin individually or with free glutamine on magnesium and BCAAs concentrations in blood serum, liver and kidneys of rats.


Assuntos
Aminoácidos de Cadeia Ramificada/metabolismo , Cádmio/metabolismo , Flavonoides/metabolismo , Glutamina/metabolismo , Chumbo/metabolismo , Magnésio/sangue , Animais , Catequina/metabolismo , Rim/metabolismo , Fígado/metabolismo , Masculino , Quercetina/metabolismo , Ratos
17.
Magnes Res ; 17(2): 79-84, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15319138

RESUMO

The neoplasmic process causes the disturbance of magnesium metabolism in the organism. The studies were conducted in order to determine magnesium concentration in the tissues and serum of dogs with malignant and non-malignant mammary tumours in comparison to its concentration in the tissue and serum of healthy dogs. From the studies presented in the paper it turns out that magnesium concentration in the mammary neoplasmic tissue increases with the increase of tumour malignancy and in comparison to its concentration in the control tissue. Magnesium concentration in the blood serum decreases with the increase of tumour malignancy and in comparison to the control tissue. Therefore it was shown that there is a connection between the degree of tumour malignancy and magnesium concentration in the tissue and serum.


Assuntos
Magnésio/metabolismo , Neoplasias Mamárias Animais/metabolismo , Animais , Cães , Feminino , Humanos , Magnésio/sangue , Neoplasias Mamárias Animais/etiologia
18.
Magnes Res ; 17(2): 94-101, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15319141

RESUMO

Wide spectrum of biological properties of magnesium is very well documented in pathomechanism of large number of diseases, where increased stressogenic actions with simultaneous magnesium deficiency have been observed. Our paper describes researches on trials to find out the relationships between stress reaction and magnesium deficiency, admission procedure and hospitalization form of children with pneumonia or obstructive bronchiolitis. It has been shown that serum magnesium concentration before treatment of sick children that during hospitalization had contacted parents, was significantly lower and essentially increased in examinations after treatment. However, in both groups of ill children (that which had constant as well as sporadic contact with parents during hospitalization period) blood cell magnesium concentration was essentially lower before and significantly increased after treatment, and urine magnesium concentration was essentially higher before and significantly decreased after treatment.


Assuntos
Bronquiolite/metabolismo , Hospitalização , Magnésio/metabolismo , Admissão do Paciente , Pneumonia/metabolismo , Criança Hospitalizada/psicologia , Feminino , Humanos , Lactente , Magnésio/sangue , Magnésio/urina , Masculino , Estresse Fisiológico/metabolismo , Estresse Fisiológico/psicologia
19.
Pol Merkur Lekarski ; 17(101): 523-7, 2004 Nov.
Artigo em Polonês | MEDLINE | ID: mdl-15754649

RESUMO

Melatonin is a hormone produced in human by the pineal body, the endocrine gland localized in the central part of cerebrum. It regulates many vital processes. Its main and best known effect is restoring the natural cycle of organism functions. It is safe and non-addictive sleep-inducing drug, which can eliminate disruptions in our circadian rhythm, in such situations as shift working, changing of time zones (during intercontinental air travelling) or insomnia. It improves mood and quality of sleep. Melatonin function consisting in stabilization of biological rhythms, free radical scavenging or immune system stimulating can delay aging processes. Its appropriate supplementation can prolong life even by decades, keeping our body in good both physical and psychological condition. Additionally, profitable for health properties of melatonin include ability to control some illnesses (prophylaxis of cardiovascular system diseases, neoplastic diseases and other functional disorders of organisms). It makes the immune system stronger, decreases susceptibility of the organism to stress, and improves mood and general feeling.


Assuntos
Ritmo Circadiano/efeitos dos fármacos , Melatonina/farmacologia , Afeto/efeitos dos fármacos , Envelhecimento/efeitos dos fármacos , Humanos , Sistema Imunitário/efeitos dos fármacos , Transtornos do Sono do Ritmo Circadiano/tratamento farmacológico
20.
Pol Merkur Lekarski ; 17(101): 528-9, 2004 Nov.
Artigo em Polonês | MEDLINE | ID: mdl-15754650

RESUMO

Melatonin occurs naturally in human organism, and its basic and the best investigated function is stabilization of biological rhythms, mainly day-night cycle. Properties very profitable for organisms, this hormone owes to its great ability of free radical scavenging and antioxidant activity. Connection between melatonin and elements occurring in human organism can be based on various relationships. Calcium ions play active role in melatonin biosynthesis, and sodium and potassium ions, thank to their properties of membranes polarization, influence melatonin penetrating possibility into cells, where this active molecule can exerts its physiologic functions. Another type of relationship exists between melatonin and zinc ions. Genomic action of melatonin appears in its ability to stimulate antioxidant genes expression, and its direct cellular action appears in increasing of these enzymes activity, among which very important place takes zinc-enzyme-superoxide dismutase (SOD). Melatonin also prevents poisoning by such elements like chromium (III) and (VI), iron and copper, through levelling toxic actions of these ions on organism. The role of melatonin in these processes relies mainly on scavenging of arisen free radicals, detoxification of hydrogen peroxide and combining excess of toxic ions into compounds harmless for organism.


Assuntos
Melatonina/metabolismo , Oligoelementos/metabolismo , Cálcio/metabolismo , Cromo/metabolismo , Cobre/metabolismo , Humanos , Ferro/metabolismo , Potássio/metabolismo , Sódio/metabolismo , Zinco/metabolismo
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