RESUMO
Concentration of abundant elements e.g. calcium as well as of elements present in trace amount e.g. zinc in mandibles of 7, 14 an 28 day old newborn rats were determined by X-ray fluorescence analysis. The measurements were carried out by using a measurement system containing X-ray tube ECLIPSE-III and X-ray and gamma ray detector XR-100T-CdTe (Amptek Inc.). Concentration of calcium and zinc depended on the region of interest on the rat's mandible due to mineralization degree conditioned by its function. Increasing age produced a remarkable increase in Ca content in contrast to Zn content in the bone tissue obtained from 7, 14 and 28 day old newborn rats. The calculated Zn/Ca concentration ratio was the biggest for 7 day old newborns and successively decreased with age indicating the important role of zinc at the beginning of bone ontogenesis.
Assuntos
Animais Recém-Nascidos/metabolismo , Calcificação Fisiológica/fisiologia , Mandíbula/metabolismo , Zinco/fisiologia , Envelhecimento , Animais , Cálcio/metabolismo , Ratos , Espectrometria por Raios XRESUMO
OBJECTIVE: Caffeic acid, predominantly as esters linked to quinic acid (chlorogenic acids), is a phenolic acid present at high levels in coffee. The aim of the study was to investigate effects of caffeic and chlorogenic acids on the skeletal system of female rats with normal estrogen levels and estrogen-deficient. MATERIALS AND METHODS: Caffeic acid (5 and 50 mg/kg p.o. daily) and chlorogenic acid (100 mg/kg p.o. daily) were administered for 4 weeks to non-ovariectomized and bilaterally ovariectomized mature Wistar rats, and their effects were compared with appropriate controls. Moreover, estradiol (0.2 mg/kg p.o. daily) was administered to ovariectomized rats. Bone turnover markers, mass, mineralization and mechanical properties were examined. RESULTS: Although caffeic acid at a low dose exerted some unfavorable effects on the skeletal system, at high doses, caffeic and chlorogenic acids slightly increased mineralization in the tibia and improved mechanical properties of the femoral diaphysis (compact bone). Unlike estradiol, they did not counteract the worsening of the tibial metaphysis bone strength (cancellous bone) and increases in osteocalcin concentration induced by estrogen deficiency. CONCLUSIONS: High doses of the phenolic acids slightly favorably affected the rat skeletal system independently of the estrogen status.
Assuntos
Osso e Ossos/efeitos dos fármacos , Ácidos Cafeicos/farmacologia , Ácido Clorogênico/farmacologia , Animais , Relação Dose-Resposta a Droga , Estradiol/sangue , Estradiol/farmacologia , Estrogênios/farmacologia , Feminino , Fêmur/efeitos dos fármacos , Humanos , Osteocalcina/sangue , Ovariectomia , Ratos , Ratos Wistar , Tíbia/efeitos dos fármacosRESUMO
In this study, we evaluated 20 of our previously synthesized peptides on isolated rat uterus by Holton's procedure with minor modifications, and compared their activity with that assessed previously by their ability to inhibit vasodepressor response to exogenous bradykinin (BK) in conscious rats. We used [D-Arg(0), Hyp(3), Thi(5, 8), (D-Phe)(7)]BK, the B(2) antagonist of Vavrek and Stewart as a model when designing our analogs. We observed that, in the case of the rat uterus test, the activity of peptides modified by acylation of the N-terminus with various bulky groups depends substantially on the chemical character of the substituent. We also learned that, contrary to previous examples, acylation of the N-terminus of antagonists, which contain a sterically restricted fragment in the C-terminal part, may not improve their antagonistic potencies. Besides an improved characterization of a series BK analogs, our studies have provided new information on the structure-activity relationship, which in turn may be of value in the design of more potent and selective bradykinin antagonists. The results of our studies appear to support the hypothesis of others about the presence of different subtypes of B(2) receptors in rat uterus and blood vessels.
Assuntos
Bradicinina/análogos & derivados , Ocitócicos/farmacologia , Tocolíticos/farmacologia , Contração Uterina/efeitos dos fármacos , Vasoconstritores/farmacologia , Animais , Relação Dose-Resposta a Droga , Feminino , Técnicas In Vitro , Ratos , Ratos Wistar , Receptor B2 da Bradicinina , Receptores da Bradicinina , Relação Estrutura-AtividadeRESUMO
Male Wistar rats were injected with fluphenazine /FLU/ i.p. in doses of 1 or 5 mg/kg for twelve months. Striatal met- and leu-enkephalin contents were determined after 1, 3, 6, 9 and 12 months of treatment, and one week after the drug withdrawal following a 12-month treatment, Enkephalin levels were significantly increased with slight fluctuations in some months and returned to normal one week after the last neuroleptic dose following a 12-month administration. Apomorphine, but not naloxone, prevented elevation of enkephalin levels after a one month FLU administration. Our findings confirm previous observations that prolonged disturbances in functions of the dopaminergic mechanism result in specific disturbances in the endogenous opioid peptide content, release and biosynthesis, and demonstrate that enkephalins are one of the factors with take part in the mechanism of neuroleptic action during a long-term treatment.
Assuntos
Corpo Estriado/análise , Encefalinas/análise , Flufenazina/farmacologia , Animais , Apomorfina/farmacologia , Encefalina Leucina/análise , Encefalina Metionina/análise , Masculino , Naloxona/farmacologia , Ratos , Ratos Endogâmicos , Receptores Dopaminérgicos/efeitos dos fármacos , Receptores Dopaminérgicos/fisiologiaRESUMO
The aim of the present study was to establish whether trimetazidine (TMZ) is capable of protecting astrocytes against hypoxic injury. Using the model of astrocyte cell culture we tried to observe the cells treated with TMZ before, during and after hypoxia simulated in vitro. Cell viability was determined by Live/Dead (viability/cytotoxicity) Assay Kit and MTT conversion test. Apoptotic cell death was distinguished by a method using fluorescence microscopy with Hoechst 33342. The effect of the drug on the DNA synthesis was evaluated by measuring the incorporation of [3H]thymidine into DNA of astrocytes. TMZ stimulates the proliferation of astrocytes most significant one when the astrocytes are exposed to the drug in normoxia, hypoxia and/or re-oxygenation. Adding TMZ into cultures during re-oxygenation and hypoxial re-oxygenation significantly decreases the number of dead and apoptotic cells. Our experiment has proved that TMZ exerts the most significantly cytoprotective effect on astrocytes in vitro when added during hypoxia and/or re-oxygenation. We may conclude that the protective effect of TMZ depends on the sequence of drug adding and hypoxia/ re-oxygenation onset.
Assuntos
Astrócitos/efeitos dos fármacos , Citoproteção/fisiologia , Trimetazidina/farmacologia , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Astrócitos/fisiologia , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Hipóxia Celular/efeitos dos fármacos , Hipóxia Celular/fisiologia , Células Cultivadas , Citoproteção/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/fisiologia , Ratos , Ratos WistarRESUMO
6-hydroxydopamine and 6-hydroxydopa injected intraperitoneally in dose of 50 microgram/g in newborn rats, two and six weeks old caused a drop in content of phosphatidylcholine and phosphatidylserine, and an increase in content of phosphatidylinositol in the brains of two weeks old rats treated with 6-hydroxydopamine in comparison with controls. 6-hydroxydopa administration caused an increase of the content of phosphatidylcholine and phosphatidylinositol and decrease of diphosphatidylglycerol in the brain of two weeks old rats. In the brains of six weeks old rats only a decrease in content of phosphatidic acid was observed after administration of either 6-hydroxydopamine or 6-hydroxydopa. The results are further evidence of a nonspecific toxic action of both compounds.
Assuntos
Encéfalo/efeitos dos fármacos , Di-Hidroxifenilalanina/farmacologia , Hidroxidopaminas/farmacologia , Fosfolipídeos/metabolismo , Animais , Encéfalo/metabolismo , Fosfatidilcolinas/metabolismo , Fosfatidilinositóis/metabolismo , Fosfatidilserinas/metabolismo , RatosRESUMO
Astrocytes play an important role in the homeostasis of the CNS both in normal conditions and after ischemic injury. The swelling of astrocytes is observed during and several seconds after brain ischemia. Then ischemia stimulates sequential morphological and biochemical changes in glia and induces its proliferation. Reactive astrocytes demonstrate stellate morphology, increased glial fibrillary acidic protein (GFAP) immunoreactivity, increased number of mitochondria as well as elevated enzymatic and non-enzymatic antioxidant activities. Astrocytes can re-uptake and metabolize glutamate and in this way they control its extracellular concentration. The ability of astrocytes to protect neurons against the toxic action of free radicals depends on their specific energy metabolism, high glutathione level, increased antioxidant enzyme activity (catalase, superoxide dismutase, glutathione peroxidase) and overexpression of antiapoptotic bcl-2 gene. Astrocytes produce cytokines (TNF-alpha, IL-1, IL-6) involved in the initiation and maintaining of immunological response in the CNS. In astrocytes, like in neurones, ischemia induces the expression of immediate early genes: c-fos, c-jun, fos B, jun B, jun D, Krox-24, NGFI-B and others. The protein products of these genes modulate the expression of different proteins, both destructive ones and those involved in the neuroprotective processes.
RESUMO
In an attempt to develop more active and selective analogues of arginine vasopressin (AVP), two peptides have been designed, synthesized and tested for vasopressor (V1-receptors) and antidiuretic (V2-receptors) activities. We also estimated the uterotonic and anti-uterotonic activities of these compounds in-vitro. The first peptide, [(L-2-Nal)3] AVP is a highly active V2-agonist. The second analogue, [(L-2-Nal)3, (D-Arg)R]VP is among the most potent antagonists of the vasopressor response to AVP. Moreover, it is the first V1-antagonist devoid of anti-uterotonic activity. High antipressor potency of the second peptide was achieved without modification of position 1.
Assuntos
Arginina Vasopressina/análogos & derivados , Receptores de Vasopressinas/efeitos dos fármacos , Animais , Arginina Vasopressina/química , Arginina Vasopressina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Diurese/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Técnicas In Vitro , Masculino , Ratos , Ratos Wistar , Contração Uterina/efeitos dos fármacosRESUMO
In this study we describe the synthesis and some pharmacological properties of six new analogues of arginine vasopressin (AVP). Five of the peptides were substituted in position 2 with L-1-naphthylalanine (L-1-Nal) or D-1-naphthylalanine (D-1-Nal); one had D-1-Nal in position 3. All analogues were tested in bioassays for pressor and antidiuretic activity. We also tested the uterotonic activity of the peptides in-vitro. Two of the new peptides were moderately potent V1a and oxytocin antagonists. The modifications proposed resulted in a drop or the removal of antidiuretic activity and in the removal of pressor activity, or conversion into moderate antagonists. Two peptides ([Mpa1, (L-1-Nal)2]AVP and [Mpal, (D-1-Nal)2]AVP) which appear not to interact with V1a and V2 receptors were exceptionally selective oxytocin antagonists in vitro. These compounds with selective oxytocin antagonistic activity may be promising candidates for the development of potential tocolytic agents for the prevention of pre-term labour.
Assuntos
Arginina Vasopressina/análogos & derivados , Ocitocina/antagonistas & inibidores , Animais , Arginina Vasopressina/farmacologia , Diurese/efeitos dos fármacos , Feminino , Técnicas In Vitro , Masculino , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Útero/efeitos dos fármacosRESUMO
A group of condensed triazole-thiazine derivatives (2a-i, 3b, 3j) was obtained in reaction of the corresponding 5-substituted 1,2,4-triazole-3-thiones (1a-j) with epichlorohydrin in alkaline medium. The structure of the compounds synthesized was confirmed by spectral and roentgenographic methods. Tuberculostatic and circulatory activities of the compounds were also studied.
Assuntos
Antituberculosos/síntese química , Fármacos Cardiovasculares/síntese química , Tiazinas/síntese química , Triazóis/síntese química , Animais , Antituberculosos/química , Antituberculosos/farmacologia , Cardiotônicos/farmacologia , Fármacos Cardiovasculares/química , Fármacos Cardiovasculares/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Masculino , Contração Muscular/efeitos dos fármacos , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Tiazinas/química , Tiazinas/farmacologia , Triazóis/química , Triazóis/farmacologiaRESUMO
The present study was initiated to examine the effect of nebracetam, a nootropic drug, on various biochemical and morphometric parameters in order to gain some insight into the mechanism of this agent action. The content of adenosine triphosphate (ATP) and phosphocreatine (PCr) and 3H-valine incorporation into proteins was measured and the morphometry was performed after nebracetam and piracetam treatment of rat astrocytes cultured in vitro with or without dibutyryl 3',5'-cyclic adenosine monophosphate (dBcAMP). Nootropics were added into the culture medium for 2 weeks at the final concentration of 10(-7) M. Cultured astrocytes treated with either nebracetam or piracetam showed decreased intracellular ATP and PCr levels. The addition of nebracetam and dBcAMP to cultures caused an increase of PCr content in astrocytes. The astrocytes treated with nebracetam showed a decrease in 3H-valine incorporation. The increase of 3H-valine incorporation into astrocytes after piracetam with dBcAMP treatment was found. Nootropic drugs change morphometric parameters (cell area, perimeter and form factor) of cultured astrocytes. It can be concluded that nootropics have differentiated influence on both the energetic metabolism and morphology of rat astrocytes in vitro.
Assuntos
Trifosfato de Adenosina/metabolismo , Astrócitos/metabolismo , Nootrópicos/farmacologia , Fosfocreatina/metabolismo , Piracetam/farmacologia , Pirrolidinonas/farmacologia , Animais , Células Cultivadas , Ratos , Ratos Wistar , Valina/metabolismoRESUMO
Gangliosides take part in synaptic transmission, neuronal metabolism and development of nervous tissue. They cooperate with nerve growth factor (NGF) and have positive influence on regeneration of the nervous system impairments. There exist many behavioural and biochemical evidences of gangliosides participation in the regeneration of experimentally injured animal nervous system. The therapeutic effectivity of gangliosides in clinical practice is encouraging. Commercial preparates of gangliosides (Cronassial, Sygen) have been successfully used in the therapy of chronic neuropathies, strokes and subarachnoidal haemorrhages. Among the adverse reactions to these drugs are: local irritation, anxiety and possible detrimental effect in immunological system. Ganglioside preparations need further clinical examinations.
Assuntos
Gangliosídeos/uso terapêutico , Doenças do Sistema Nervoso/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Transtornos Cerebrovasculares/tratamento farmacológico , Transtorno Depressivo/induzido quimicamente , Feminino , Gangliosídeos/efeitos adversos , Gangliosídeos/farmacologia , Humanos , Sistema Imunitário/efeitos dos fármacos , Masculino , Regeneração Nervosa/efeitos dos fármacos , Condução Nervosa/efeitos dos fármacos , Hemorragia Subaracnóidea/tratamento farmacológicoRESUMO
Male Wistar rats were treated intraperitoneally once per week for 12 weeks with following detergents: Olbrotol-18 (nonionic detergent), a product of etheric condensation of 18 moles of ethylene oxide to 1 mole of the mixture of olein alcohol and cetyl alkohol in ratio 1:1, in a dose of 10 mg/kg; SBO (anionic detergent), sodium 2-ethylhexylsulfosuccinate, in a dose of 10 mg/kg and Sterinol (cationic detergent), benzalkonium bromide, in a dose of 0.6 mg/kg. The control rats were injected with 0.9% saline solution. The content of total cholesterol, beta-lipoproteins and total lipids in serum were estimated. The increase of total cholesterol and the decrease of beta-lipoproteins content in serum of rats after all used detergents were observed as compared with the control. The increase of total lipid content only after long-term treatment with Olbrotol-18 was found. It is concluded that long term intraperitoneal treatment with detergents changes similarly the contents of total cholesterol and of beta-lipoproteins in blood serum of rats.
Assuntos
Detergentes/farmacologia , Lipídeos/sangue , Animais , Colesterol/sangue , Detergentes/administração & dosagem , Injeções Intraperitoneais , Lipoproteínas LDL/sangue , Masculino , RatosRESUMO
Lecithin-cholesterol acyltransferase (LCAT) is involved in esterify of free cholesterol and in the cholesterol esters transport from peripheral tissues to the liver. Genetically dependent lack of enzyme activity leads to Fish Eye Disease and to familial LCAT deficiency. There are specific abnormalities of plasma lipids and lipid deposits in multiple tissues (familial LCAT deficiency) or in corneal only (Fish Eye Disease). Clinical features of familial LCAT deficiency include corneal opacities, anemia, and proteinuria. Renal failure is the most frequent complication, occurring in the fourth decade. Treatment of familial LCAT deficiency is based on infusions of plasma or whole blood and on kidney transplantation.
Assuntos
Deficiência da Lecitina Colesterol Aciltransferase/diagnóstico , Humanos , Deficiência da Lecitina Colesterol Aciltransferase/terapiaRESUMO
The goal of the present study is to assess the effects of anticancer treatment with cyclophosphamide and cytarabine during pregnancy on the mineralization of mandible bones in 7-, 14- and 28-day-old rats. Each bone sample was described by its X-ray fluorescence spectrum characterizing the mineral composition. The data collected are multivariate in nature and their structure is difficult to visualize and interpret directly. Therefore, methods like analysis of variance-principal component analysis (ANOVA-PCA) and ANOVA-simultaneous component analysis (ASCA), which are suitable for the analysis of highly correlated spectral data and are able to incorporate information about the underlined experimental design, are greatly valued. In this study, the ASCA methodology adapted for unbalanced data was used to investigate the impact of the anticancer drug treatment during pregnancy on the mineralization of the mandible bones of newborn rats and to examine any changes in the mineralization of the bones over time. The results showed that treatment with cyclophosphamide and cytarabine during pregnancy induces a decrease in the K and Zn levels in the mandible bones of newborns. This suppresses the development of mandible bones in rats in the early stages (up to 14 days) of formation. An interesting observation was that the levels of essential minerals like K, Mg, Na and Ca vary considerably in the different regions of the mandible bones.