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1.
Neurobiol Learn Mem ; 205: 107846, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37865261

RESUMO

A single bout of cardiovascular exercise (CE) performed after practice can facilitate the consolidation of motor memory. However, the effect is variable and may be modulated by different factors such as the motor task's or participant's characteristics and level of awareness during encoding (implicit vs explicit learning). This study examines the effects of acute CE on the consolidation of motor sequences learned explicitly and implicitly, exploring the potential moderating effect of fitness level and awareness. Fifty-six healthy adults (24.1 ± 3.3 years, 32 female) were recruited. After practicing with either the implicit or explicit variant of the Serial Reaction Time Task (SRTT), participants either performed a bout of 16 min of vigorous CE or rested for the same amount of time. Consolidation was quantified as the change in SRTT performance from the end of practice to a 24 h retention test. Fitness level (V̇O2peak) was determined through a graded exercise test. Awareness (implicit vs explicit learning) was operationalized using a free recall test conducted immediately after retention. Our primary analysis indicated that CE had no statistically significant effects on consolidation, regardless of the SRTT's variant utilized during practice. However, an exploratory analysis, classifying participants based on the level of awareness gained during motor practice, showed that CE negatively influenced consolidation in unfit participants who explicitly acquired the motor sequence. Our findings indicate that fitness level and awareness in sequence acquisition can modulate the interaction between CE and motor memory consolidation. These factors should be taken into account when assessing the effects of CE on motor memory.


Assuntos
Aprendizagem , Consolidação da Memória , Adulto , Humanos , Feminino , Exercício Físico , Tempo de Reação , Rememoração Mental , Destreza Motora
2.
Mol Pharm ; 13(9): 2966-76, 2016 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-27149661

RESUMO

The purpose of this research was to determine the potential use of water-soluble anionic and cationic carbosilane dendrimers (generations 1-3) as mucoadhesive polymers in eyedrop formulations. Cationic carbosilane dendrimers decorated with ammonium -NH3(+) groups were prepared by hydrosylilation of Boc-protected allylamine and followed by deprotection with HCl. Anionic carbosilane dendrimers with terminal carboxylate groups were also employed in this study. In vitro and in vivo tolerance studies were performed in human ocular epithelial cell lines and rabbit eyes respectively. The interaction of dendrimers with transmembrane ocular mucins was evaluated with a surface biosensor. As proof of concept, the hypotensive effect of a carbosilane dendrimer eyedrop formulation containing acetazolamide (ACZ), a poorly water-soluble drug with limited ocular penetration, was tested after instillation in normotensive rabbits. The methodology used to synthesize cationic dendrimers avoids the difficulty of obtaining neutral -NH2 dendrimers that require harsher reaction conditions and also present high aggregation tendency. Tolerance studies demonstrated that both prototypes of water-soluble anionic and cationic carbosilane dendrimers were well tolerated in a range of concentrations between 5 and 10 µM. Permanent interactions between cationic carbosilane dendrimers and ocular mucins were observed using biosensor assays, predominantly for the generation-three (G3) dendrimer. An eyedrop formulation containing G3 cationic carbosilane dendrimers (5 µM) and ACZ (0.07%) (289.4 mOsm; 5.6 pH; 41.7 mN/m) induced a rapid (onset time 1 h) and extended (up to 7 h) hypotensive effect, and led to a significant increment in the efficacy determined by AUC0(8h) and maximal intraocular pressure reduction. This work takes advantage of the high-affinity interaction between cationic carbosilane dendrimers and ocular transmembrane mucins, as well as the tensioactive behavior observed for these polymers. Our results indicate that low amounts of cationic carbosilane dendrimers are well tolerated and able to improve the hypotensive effect of an acetazolamide solution. Our results suggest that carbosilane dendrimers can be used in a safe range of concentrations to enhance the bioavailability of drugs topically administered in the eye.


Assuntos
Dendrímeros/química , Dendrímeros/farmacocinética , Silanos/química , Silanos/farmacocinética , Acetazolamida/química , Administração Oftálmica , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dendrímeros/administração & dosagem , Dendrímeros/farmacologia , Humanos , Masculino , Coelhos , Silanos/administração & dosagem , Silanos/farmacologia , Ressonância de Plasmônio de Superfície
3.
Biochim Biophys Acta ; 1801(4): 430-7, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20005974

RESUMO

The aim of this study was to determine the apoptotic pathways and mechanisms involved in electronegative LDL [LDL(-)]-induced apoptosis in RAW 264.7 macrophages and the role of Nrf2 in this process. Incubation of RAW 264.7 macrophages with LDL(-) for 24 h resulted in dose-dependent cell death. Activated caspases were shown to be involved in the apoptosis induced by LDL(-); incubation with the broad caspase inhibitor z-VAD prevented apoptosis in LDL(-)-treated cells. CD95 (Fas), CD95 ligand (FasL), CD36 and the tumor necrosis factor (TNF) ligand Tnfsf10 were overexpressed in LDL(-)-treated cells. However, Bax, Bcl-2 and Mcl-1 protein levels remained unchanged after LDL(-) treatment. LDL(-) promoted hyperpolarization of the mitochondrial membrane, elevated reactive oxygen species (ROS) production and translocation of Nrf2 to the nucleus, a process absent in cells treated with native LDL. Elicited peritoneal macrophages from Nrf2-deficient mice exhibited an elevated apoptotic response after challenge with LDL(-), together with an increase in the production of ROS in the absence of alterations in CD36 expression. These results provide evidence that CD36 expression induced by LDL(-) is Nrf2-dependent. Also, it was demonstrated that Nrf2 acts as a compensatory mechanism of LDL(-)-induced apoptosis in macrophages.


Assuntos
Apoptose , Lipoproteínas LDL/metabolismo , Macrófagos Peritoneais/patologia , Fator 2 Relacionado a NF-E2/fisiologia , Animais , Biomarcadores/metabolismo , Western Blotting , Antígenos CD36/genética , Antígenos CD36/metabolismo , Proteína Ligante Fas/genética , Proteína Ligante Fas/metabolismo , Feminino , Imunofluorescência , Perfilação da Expressão Gênica , Humanos , Macrófagos Peritoneais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
4.
Br J Pharmacol ; 152(2): 249-55, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17618303

RESUMO

BACKGROUND AND PURPOSE: The kaurane diterpenes foliol and linearol are inhibitors of the activation of nuclear factor kappaB, a transcription factor involved in the inflammatory response. Effects of these diterpenes on apoptosis and phagocytosis have been analysed in cultured peritoneal macrophages and in the mouse macrophage cell line, RAW 264.7. EXPERIMENTAL APPROACH: Macrophages were maintained in culture and activated with pro-inflammatory stimuli in the absence or presence of diterpenes. Apoptosis and the phagocytosis in these cells under these conditions were determined. KEY RESULTS: Incubation of macrophages with a mixture of bacterial lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma) induced apoptosis through a NO-dependent pathway, an effect significantly inhibited by foliol and linearol in the low muM range, without cytotoxic effects. Apoptosis in macrophages induced by NO donors was also inhibited. The diterpenes prevented apoptosis through a mechanism compatible with the inhibition of caspase-3 activation, release of cytochrome c to the cytosol and p53 overexpression, as well as an alteration in the levels of proteins of the Bcl-2 family, in particular, the levels of Bax. Cleavage of poly(ADP-ribose) polymerase, a well-established caspase substrate, was reduced by these diterpenes. Treatment of cells with foliol and linearol decreased phagocytosis of zymosan bioparticles by RAW 264.7 cells and to a greater extent by peritoneal macrophages. CONCLUSIONS AND IMPLICATIONS: Both diterpenes protected macrophages from apoptosis and inhibited phagocytosis, resulting in a paradoxical control of macrophage function, as viability was prolonged but inflammatory and phagocytic functions were impaired.


Assuntos
Apoptose/efeitos dos fármacos , Diterpenos do Tipo Caurano/farmacologia , Diterpenos/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Óxido Nítrico/metabolismo , Animais , Caspase 3/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocromos c/metabolismo , Interferon gama/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/fisiologia , Masculino , Camundongos , Óxido Nítrico Sintase Tipo II/metabolismo , Fagocitose , Substâncias Protetoras/farmacologia , Proteínas Recombinantes , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismo
5.
Rev Esp Quimioter ; 20(4): 442-5, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18563218

RESUMO

Genomic mutations occurring during reverse transcription of hepatitis B virus (HBV) could explain its genetic diversity and account for 8 genetically distinct genotypes that are geographically distributed quite differently. The main objectives of this study were to determine the prevalence of hepatitis B virus genotypes in patients with chronic hepatitis B and to see if there was a relationship between genotypes and risk factors for transmission based on HBeAg status. A total of 14 serum samples were analyzed using INNO-LIPA HBV genotyping assay. Genotype D was the most prevalent (64.3%) followed by genotype A (28.6%). There was one case of co-infection (D/E genotypes) that was confirmed by PCR sequencing. All patients except one were HBeAg-negative and anti-HBe-positive. The risk factors for HBV transmission were unknown in half of the cases; in the other half, sexual, transfusion, maternal or interfamilial transmission were observed. The results show that genotype D is the most prevalent genotype in our hospital, followed by genotype A. On the other hand, no relationship was found between HBeAg status and genotype.


Assuntos
Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Adolescente , Adulto , Feminino , Genótipo , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Hepatite B Crônica/transmissão , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
6.
J Biomed Mater Res A ; 78(2): 343-51, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16646066

RESUMO

Poly(L-valine-L-proline-L-alanine-L-valine-L-glycine) (VPAVG) is a new kind of proteinaceous polymer belonging to the Elastin-like family. These polymers are based on the recurrence of certain short peptide monomers that are considered as "building blocks" in the natural elastin. This smart thermoresponsive polymer has the ability to self-associate at physiological temperature to form aggregates with about 60% in water. This ability can be harnessed to prepare microparticles loaded with an active substance. The aim of this report is to evaluate, from the results of the experiment conducted, the biocompatibility of microparticles prepared from poly(VPAVG). We have studied the cytotoxic effects of microparticles, edema formation after subcutaneous injection (1 and 2.5 mg) in rats (n = 6), and also intraocular tolerance after the intravitreal injection of 2.5 mg of poly(VPAVG) microparticles into pigmented rabbits (n = 12). The polymer did not induce any cytotoxicity or nonspecific depression of cellular respiration on macrophages under the range of polymer concentrations investigated in this study (20, 30, 40, and 60 mg/mL). We observed no inflammatory response to microparticles after subcutaneous injection in the hind-paw of rats, with no significant differences between the control group (PBS) and experimental groups. Anterior and posterior segment signs were evaluated after intraocular injection of poly(VPAVG) microparticles. Only a few eyes (2/11) of the experimental group presented inflammation signs at day 28 postinjection. Nevertheless, 45% (5/11) of the eyes receiving microparticles showed tractional retinal detachment. The results observed in this work suggested certain fibroblastic activity induced by poly(VPAVG) microparticles after their intraocular injection.


Assuntos
Materiais Biocompatíveis , Elastina , Macrófagos Peritoneais/citologia , Peptídeos/química , Peptídeos/farmacologia , Alanina , Sequência de Aminoácidos , Animais , Sobrevivência Celular/efeitos dos fármacos , Conjuntivite/prevenção & controle , Edema/prevenção & controle , Glicina , Macrófagos Peritoneais/efeitos dos fármacos , Camundongos , Microscopia Eletrônica de Varredura , Peso Molecular , Peptídeos/administração & dosagem , Prolina , Valina , Corpo Vítreo/efeitos dos fármacos , Difração de Raios X
7.
Rev Esp Med Nucl Imagen Mol ; 35(6): 358-364, 2016.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27246292

RESUMO

PURPOSE: Our objective was to analyse the accuracy of the sentinel node biopsy, taking into consideration the scintigraphy detection rate after the intratumoural administration of the radiopharmaceutical in patients with breast cancer who received neoadjuvant chemotherapy. MATERIALS AND METHODS: The study included 60 patients with a diagnosis of invasive breast carcinoma, stage T1-T3, who received treatment with neoadjuvant chemotherapy, and were subsequently subjected to breast surgery and sentinel node biopsy after intra-tumour administration of the radiopharmaceutical. RESULTS: Scintigraphic detection of some sentinel node was achieved in 55/60 patients (91.6%). When those cases that received a second injection of the radiopharmaceutical, performed peri-areolarly due to a lack of tracer migration, were excluded, the detection rate dropped to 70% (42/60). When the detection of sentinel node, or its absence, was compared in those 42 patients, no differences were found with age, laterality-location of the lesion, size pre- and post-neoadjuvant chemotherapy, histological grade, or immunohistochemical profile. There were significant differences when comparing the groups according to the degree of pathological tumour response, both with the Miller-Payne system (non-detection 44.4%-detection 16.7%, p = 0.003) as well as the residual cancer burden (72.2%-28.6%, p<0.01). CONCLUSIONS: The scintigraphic detection of the sentinel node after intratumoural administration of the radiopharmaceutical in patients with breast cancer who received neoadjuvant chemotherapy was below the optimal value, and sometimes a further, peri-areolar, injection was necessary, probably in relation to an alteration in the lymphatic drainage pathways. There was a significant inverse relationship between the detection of the sentinel node and level of pathological tumour response.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Cintilografia , Compostos Radiofarmacêuticos/administração & dosagem , Biópsia de Linfonodo Sentinela , Agregado de Albumina Marcado com Tecnécio Tc 99m/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Feminino , Humanos , Injeções Intralesionais , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estudos Retrospectivos
8.
Curr Top Med Chem ; 3(2): 171-85, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12570772

RESUMO

Natural products research has lately undergone exponential growth owing to advances in isolation techniques and in synthetic methods design, as well as for the identification of a wide range of biological properties exhibited by these compounds. In the present review, general remarks on the chemical features, biosynthetic pathways, isolation and structure elucidation of terpenoids are briefly discussed. In addition to this, recent work done on anti-inflammatory terpenoids (diterpenoids, triterpenoids and sesquiterpene lactones) with special emphasis on the last new molecular targets evaluated is presented.


Assuntos
Anti-Inflamatórios não Esteroides , Inflamação/tratamento farmacológico , Terpenos , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Anti-Inflamatórios não Esteroides/uso terapêutico , Humanos , Estrutura Molecular , Terpenos/química , Terpenos/isolamento & purificação , Terpenos/uso terapêutico
9.
Br J Pharmacol ; 128(3): 605-12, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10516639

RESUMO

1. Andalusol, ent-6alpha,8alpha,18-trihydroxy-13(16),14-labdadiene, is a naturally occurring diterpene, isolated from Sideritis foetens (Lamiaceae). This compound exhibited therapeutic activity when evaluated in in vivo models of paw and ear inflammation (Navarro et al., 1997: Z. Naturforsch., 52, 844-849). The pharmacological effects of this diterpene have been analysed on the activation of the macrophage cell line J774 with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). 2. Incubation of J774 macrophages with andalusol (0.1 - 100 microM) inhibited the synthesis of nitrite caused by LPS (1 microg ml-1) in concentration and time-dependent manners. The maximal inhibition was observed when andalusol was added 30 min before LPS stimulation and decreased progressively as the interval between andalusol and LPS challenge increased up to 14 h. 3. Incubation of J774 cells with LPS resulted in the expression of NOS-2 protein (130 kDa) as identified by Western blot analysis. The levels of this enzyme decreased significantly in the presence of andalusol (IC50=10.5 microM), suggesting that this diterpene inhibited NOS-2 expression. 4. Andalusol inhibited nuclear factor kappaB activation, a transcription factor necessary for NOS-2 expression in response to LPS and IFN-gamma. This compound also inhibited the degradation of IkappaBalpha favouring the retention of the inactive NF-kappaB complexes in the cytosol. 5. Related compounds to andalusol but lacking the polyol groups were less effective inhibiting NOS-2 expression in LPS-activated macrophages. The present findings provide a mechanism by which the anti-inflammatory properties of this diterpene could be mediated.


Assuntos
Diterpenos/farmacologia , Macrófagos/efeitos dos fármacos , NF-kappa B/metabolismo , Óxido Nítrico Sintase/antagonistas & inibidores , Animais , Sequência de Bases , Linhagem Celular , DNA , Inibidores Enzimáticos/farmacologia , Macrófagos/enzimologia , Camundongos , Nitritos/metabolismo
10.
Biochem Pharmacol ; 51(6): 863-8, 1996 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-8602884

RESUMO

The diterpenoid ent-8alpha-hydroxy-labda-13(16),14-dien ("labdane F2") was obtained from an anti-inflammatory extract of Sideritis javalambrensis. Labdane F2 inhibited prostaglandin E2 generation in cultured mouse peritoneal macrophages, treated with zymosan, ionophore A23187, or arachidonic acid itself, and in J774 macrophage-like cells activated by bacterial lipopolysaccharide (LPS). The mechanism was investigated by prelabelling the macrophages with radiolabelled arachidonic acid or oleic acid, followed by cell activation in the presence or absence of nontoxic concentrations of labdane F2. Surprisingly, under those conditions in which reduced PGE2 generation was observed, labdane F2 consistently enhanced the release of labelled fatty acid, in a manner similar to that displayed by thimerosal a known acyl-CoA: lysolecithin transferase inhibitor. Labdane E2 therefore appears to possess 2 mutually opposing actions on the eicosanoid system in macrophages: potentiation of delivery of substrate following cell activation, followed by inhibition of conversion of substrate to product. It was also found that nontoxic concentrations of labdane F2 reduced the expression of the inducible isoforms of cyclooxygenase and nitric oxide synthase in LPS-treated J774 cells. Thus, this anti-inflammatory diterpenoid labdane possesses a diverse array of effects impinging on enzyme pathways involved in eicosanoid generation and other inflammatory pathways in macrophages.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Ácido Araquidônico/metabolismo , Diterpenos/farmacologia , Eicosanoides/biossíntese , Ativação de Macrófagos/fisiologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Naftóis/farmacologia , Extratos Vegetais/farmacologia , Animais , Ácido Araquidônico/biossíntese , Dinoprostona/biossíntese , Lipopolissacarídeos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Óxido Nítrico/biossíntese , Óxido Nítrico/toxicidade , Ácido Oleico , Ácidos Oleicos/metabolismo , Fosfolipídeos/metabolismo , Plantas/química , Estimulação Química
11.
Biochem Pharmacol ; 48(3): 445-51, 1994 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-8068031

RESUMO

Sixteen synthetic or plant-derived coumarins of dietary importance with different patterns of substitution were tested for their capacity to scavenge superoxide and for their cytotoxicity. Superoxide was generated by human polymorphonuclear leukocytes stimulated by phorbol myristate acetate and was measured using the reduction of ferricytochrome c or of nitrobule tetrazolium (NBT). Eleven of the coumarins, all lacking dihydroxy substitution, did not scavenge superoxide. Of the remaining five, the most potent scavenger was fraxetin (7,8-dihydroxy-6-methoxycoumarin) with an IC50 (concentration producing 50% inhibition) of 2.3 microM in the cytochrome assay and 5.8 microM using NBT. The other four coumarins (all containing ortho-dihydroxy catechol functions, and found previously to be pro-oxidant in cell-free systems by virtue of reduction of ferric to ferrous ions), themselves rapidly reduced cytochrome c. Therefore their effects on superoxide were measured using NBT, yielding IC50 values in the range 8.5 to 82.0 microM. Fraxetin and the other active and inactive coumarins were not directly cytotoxic at 100 microM to leukocytes or to erythrocytes, as shown by their failure to cause release of cytosolic lactate dehydrogenase or to cause haemolysis, respectively. However, all five dihydroxylated pro-oxidant coumarins were toxic to NS20Y neuroblastoma cells in 24 hr culture, whereas the other eleven coumarins were nontoxic. We conclude that 7,8-dihydroxylated coumarins such as fraxetin are agents which are not themselves directly cytotoxic and are capable of direct scavenging of superoxide anion radicals, an action which might be protective at sites of leukocyte activation during inflammation. However, in the presence of free ferric ions they may exert potentially damaging pro-oxidant actions, including cytotoxicity. This series of compounds provides a useful basis for structure-activity studies designed to achieve separation or combination of these properties.


Assuntos
Cumarínicos/toxicidade , Leucócitos/efeitos dos fármacos , Animais , Linhagem Celular , Sobrevivência Celular , Sequestradores de Radicais Livres , Humanos , L-Lactato Desidrogenase/análise , Leucócitos/metabolismo , Camundongos , Neutrófilos/efeitos dos fármacos , Consumo de Oxigênio , Superóxidos/metabolismo , Acetato de Tetradecanoilforbol/farmacologia
12.
Life Sci ; 70(3): 269-78, 2001 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-12005260

RESUMO

Six diterpenes (three clerodanes, two abietanes and one rosane) were tested for interactions with the cyclooxygenase and 5-lipoxygenase pathways of arachidonate metabolism and for effects of nitric oxide production. Two abietane diterpenes, aethiopinone and 11,12-dihydroxy-6-oxo-8,11,13-abietatriene and the rosane lagascatriol showed a remarkable effect on COX-1 pathway of PGE2 release in calcium ionophore A23187-stimulated peritoneal macrophages. Only the two latter diterpenes showed inhibition on COX-2 pathway of PGE2 release in E. coli LPS-stimulated peritoneal macrophages. In addition, all compounds assayed were inhibitors of LTC4 release with IC50 < or = 10 microM. Clerodane diterpenes were inactive in COX assay. None of the diterpenes assayed, except 11,12-dihydroxy-6-oxo-8,11,13-abietatriene, affected NO production. The results obtained suggest that the cellular mechanisms of action of some of these substances may involve inhibition of cyclooxygenase/lipoxygenase pathways and nitric oxide production.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Diterpenos/farmacologia , Eicosanoides/biossíntese , Macrófagos Peritoneais/efeitos dos fármacos , Animais , Ciclo-Oxigenase 2 , Dinoprostona/biossíntese , Isoenzimas/metabolismo , Leucotrieno C4/biossíntese , Macrófagos Peritoneais/metabolismo , Masculino , Camundongos , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo
13.
J Pharm Pharmacol ; 53(11): 1533-9, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11732756

RESUMO

The pentacyclic triterpene lupeol has been studied for its inhibitory effects on murine models of inflammation and peritoneal macrophage functions in-vitro. Lupeol (0.5 and 1 mg/ear) administered topically suppressed the mouse ear oedema induced by 12-0-tetradecanoyl-phorbol acetate (TPA), being less effective on ear oedema induced by arachidonic acid. Quantitation of the neutrophil specific marker myeloperoxidase demonstrated that its topical activity was associated with reduction in cell infiltration into inflamed tissues. When tested in-vitro, lupeol significantly reduced prostaglandin E2 (PGE2) production from A23187-stimulated macrophages, but failed to affect leukotriene C4 release. It was a weak inhibitor of nitrite release, but dose-dependently suppressed PGE2. Cytokine production (tumour necrosis factor-alpha and interleukin-1beta) was inhibited in the range 10-100 microM in lipopolysaccharide-treated macrophages. This study demonstrated that lupeol possessed anti-inflammatory activity which was likely to depend on its ability to prevent the production of some pro-inflammatory mediators.


Assuntos
Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Fitoterapia , Pimenta , Triterpenos/farmacologia , Animais , Ácido Araquidônico/farmacologia , Citocinas/metabolismo , Dinoprostona/metabolismo , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Edema/prevenção & controle , Interleucina-1/metabolismo , Leucotrieno C4/metabolismo , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Masculino , Camundongos , Modelos Animais , Nitritos/metabolismo , Triterpenos Pentacíclicos , Extratos Vegetais/farmacologia , Acetato de Tetradecanoilforbol/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
14.
J Pharm Pharmacol ; 53(6): 867-72, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11428663

RESUMO

The anti-inflammatory activity of abietic acid, a diterpene isolated from Pimenta racemosa var. grissea (Myrtaceae), was evaluated in-vivo and in-vitro. This compound significantly inhibited rat paw oedema induced by carrageenan in a time- and dose-dependent manner, and mouse ear oedema induced by 12-O-tetradecanoylphorbol acetate, after oral or topical administration. The inhibition of myeloperoxidase enzyme showed that its topical activity was influenced by neutrophil infiltration into the inflamed tissues (ears). In addition, the effect of abietic acid on some macrophage functions was analysed in-vitro. Non-toxic concentrations of abietic acid inhibited prostaglandin E2 (PGE2) production in lipopolysaccharide-treated macrophages, whereas nitrite, tumour necrosis factor alpha and interleukin-1beta production were only weakly affected by this diterpene. PGE2 production from A23187-stimulated macrophages was only inhibited at high doses (100 microM) and it failed to modify leukotriene C4 production. These results indicate that abietic acid exerts in-vivo anti-inflammatory activity after oral or topical administration and has partial ability to prevent the production of some inflammatory mediators.


Assuntos
Abietanos , Diterpenos/farmacologia , Fibrinolíticos/farmacologia , Inflamação , Infiltração de Neutrófilos/efeitos dos fármacos , Fenantrenos/farmacologia , Extratos Vegetais/farmacologia , Administração Oral , Administração Tópica , Animais , Citocinas/efeitos dos fármacos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Macrófagos/fisiologia , Masculino , Camundongos , Ratos , Ratos Wistar
15.
J Pharm Pharmacol ; 53(8): 1163-8, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11518028

RESUMO

Phytochemical and biological studies aimed at the discovery and development of novel antiinflammatory agents from natural sources have been conducted in our laboratory for a number of years. In this communication, three naturally occurring furocoumarins (imperatorin, isoimperatorin and prantschimgin) were evaluated as potential inhibitors of some macrophage functions involved in the inflammatory process. These furocoumarins have been tested in two experimental systems: ionophore-stimulated mouse peritoneal macrophages serve as a source of cyclooxygenase-1 and 5-lipoxygenase, and mouse peritoneal macrophages stimulated with E. coli lipopolysaccharide are the means of testing for anti-cyclooxygenase-2 and nitric-oxidesynthase activity. All above-mentioned furocoumarins showed significant effect on 5-lipoxygenase (leukotriene C4) with IC50 values of < 15 microM. Imperatorin and isoimperatorin exhibited strong-to-medium inhibition on cyclooxygenase-1- and cyclooxygenase-2-catalysed prostaglandin E2 release, with inhibition percentages similar to those of the reference drugs, indometacin and nimesulide, respectively. Of the three furocoumarins, only imperatorin caused a significant reduction of nitric oxide generation. Imperatorin and isoimperatorin can be classified as dual inhibitors, since it was evident that both cyclooxygenase and lipoxygenase pathways of arachidonate metabolism were inhibited by these compounds. However, selective inhibition of the 5-lipoxygenase pathway is suggested to be the primary target of action of prantschimgin.


Assuntos
Fármacos Dermatológicos/farmacologia , Furocumarinas/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Fármacos Dermatológicos/isolamento & purificação , Dinoprostona/metabolismo , Furocumarinas/isolamento & purificação , Leucotrieno C4/metabolismo , Macrófagos Peritoneais/metabolismo , Masculino , Camundongos , Óxido Nítrico/biossíntese
16.
J Ethnopharmacol ; 41(1-2): 15-7, 1994 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8170155

RESUMO

Hexane, dichloromethane, ethyl acetate and methanol extracts of Sideritis javalambrensis Pau were examined for their anti-inflammatory activity against adjuvant-carrageenan-induced inflammation and compared with phenylbutazone. In the chronic stage of inflammation, the hexane and methanol extracts showed the greatest inhibitory activity. None of the extracts inhibited inflammation in the acute phase.


Assuntos
Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/uso terapêutico , Inflamação/tratamento farmacológico , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Animais , Carragenina , Modelos Animais de Doenças , Inflamação/induzido quimicamente , Masculino , Ratos , Ratos Wistar
17.
J Ethnopharmacol ; 61(2): 161-6, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9683347

RESUMO

Ethanolic extracts from 15 plant species, representing eight different families, used in traditional medicine in Ecuador were evaluated for antiinflammatory and antioxidant activities. Conyza floribunda, Eupatorium articulatum, Bonafousia longituba, Bonafousia sananho, Tagetes pusilla and Piper lenticellosum extracts showed a significant antiinflammatory activity in vivo in the carrageenan-induced paw oedema model in mice. The extracts were also tested in vitro for their ability to inhibit lipid peroxidation and to scavenge superoxide and hydroxyl radicals. E. articulatum extract possesses both activities. Baccharis trinervis, E. articulatum and Phytolacca rivinoides extracts were active as antioxidants.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Medicina Tradicional , Plantas Medicinais/química , Animais , Equador , Edema/induzido quimicamente , Edema/prevenção & controle , Etanol , Feminino , Sequestradores de Radicais Livres/farmacologia , Radical Hidroxila/metabolismo , Técnicas In Vitro , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Microssomos/efeitos dos fármacos , Microssomos/metabolismo , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Superóxidos/metabolismo , Xantina Oxidase/metabolismo
18.
Rev Esp Quimioter ; 16(3): 325-9, 2003 Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-14702125

RESUMO

The most important aim of this study was to describe the hypothetical relationship between the PePHD region variability (related to the synthesis of a cellular enzyme pseudosubstrate) of the hepatitis C virus and the response of patients to interferon therapy. This interaction could be a determining factor in the antiviral effect of interferon. All samples (from 24 patients with chronic hepatitis C infection) were analyzed using a previously described method based on RT-PCR and nested PCR mediated by single-strand conformation polymorphism assay (SSCP). The patients were divided into three groups with respect to the response to therapy: 8 patients with sustained response, 8 patients with transient response and 8 nonresponders. In all samples a low genetic heterogeneity pattern was detected, which was independent of other factors involved in the lack of response to treatment, such as age, sex or viral genotype. This genetic homogeneity is an indirect indication of the importance of the region on viral persistence. However, more studies are needed to evaluate the real role of this sequence on the interaction between cells and the virus.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Interferon-alfa/uso terapêutico , Adulto , Antivirais/farmacologia , Feminino , Variação Genética , Hepacivirus/efeitos dos fármacos , Humanos , Interferon-alfa/farmacologia , Masculino
19.
Rev Esp Quimioter ; 15(1): 49-54, 2002 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-12582437

RESUMO

The aim of this study was to evaluate the relationship between the quasispecies in the HVR1 region of the hepatitis C virus and treatment evolution in order to determine whether genetic complexity is predictive of response to interferon therapy. The samples were analyzed by nested RT-PCR-mediated single-strand conformation polymorphism assay (SSCP). Twelve patients with chronic hepatitis C were studied and divided into three groups: three patients with sustained response, three patients with transient response and six nonresponders. The patients in the sustained response group showed a low genetic complexity pattern. By contrast, in three nonresponders and in one patient with transient response, the SSCP assay revealed a high complexity pattern. With regard to the remaining patients with transient response, new SSCP bands appeared, thereby modifying their genetic complexity pattern. Therefore, nonresponse to interferon treatment could be related to the presence of a high genetic complexity pattern, while the detection of a low genetic complexity pattern is necessary for a positive response to interferon therapy. Due to the limited number of patients involved in this study, it was not possible to predict the response to interferon based on the genetic complexity pattern. Larger studies are therefore required.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/classificação , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Interferon-alfa/uso terapêutico , Humanos
20.
Acta Cytol ; 44(2): 237-41, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10740613

RESUMO

BACKGROUND: Carcinocythemia, the presence of circulating cancer cells in peripheral blood, is a rare complication of solid neoplasms. When the number of such cells is very high, they can be detected during routine laboratory tests. They are associated with a dismal prognosis. CASE REPORT: Carcinocythemia occurred in a patient with disseminated breast cancer. Eighteen cases were identified from a review of the literature. The most common neoplasms associated with circulating cancer cells in peripheral blood were breast adenocarcinoma, small cell lung carcinoma and rhabdomyosarcoma. All the patients had stage IV disease at the time of diagnosis, and all had involvement of the reticuloendothelial system. Patients survived for an average of a few days or weeks. CONCLUSION: Circulating cancer cells in peripheral blood are an unusual manifestation of disseminated neoplasms that occurs as a terminal event.


Assuntos
Adenocarcinoma/sangue , Neoplasias da Mama/sangue , Células Neoplásicas Circulantes/patologia , Adenocarcinoma/complicações , Adenocarcinoma/secundário , Idoso , Medula Óssea/patologia , Neoplasias da Mama/complicações , Neoplasias da Mama/patologia , Feminino , Humanos
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