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B de las Heras

Publications and source records attributed to B de las Heras.

At least 19 recordsLinked to original sources
PubMed2003

Terpenoids: sources, structure elucidation and therapeutic potential in inflammation.

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.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

[Hepatitis C virus variability and interferon-mediated pathway inhibition].

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.

Adult↗
PubMed2002

[Viral quasispecies and their implications in antiviral therapy].

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.

Antiviral Agents↗
PubMed2001

Effects of six diterpenes on macrophage eicosanoid biosynthesis.

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.

Animals↗
PubMed2001

Pharmacological modification of endogenous antioxidant enzymes by ursolic acid on tetrachloride-induced liver damage in rats and primary cultures of rat hepatocytes.

The purpose of this study was to investigate possible protective effects of ursolic acid against CCl4-induced alterations of antioxidant defence enzymes in vivo as well as its effects against CCl4-intoxication in vitro. Pre-treatment of rats with ursolic acid significantly reduced serum levels of glutamate-oxalate-transaminase and glutamate-pyruvate-transaminase previously increased by administration of CCl4. Treatment with ursolic acid also significantly reversed the decreased superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase activities and glutathione levels in the liver, as the concentration of reduced glutathione was increased and the content of oxidized glutathione decreased in ursolic acid treated groups. Levels of lipid peroxidation were higher in the CCl4 group but the increase was also reduced after drug treatment (p < 0.01 for 1, 2.5 and 5 mmol/kg). In vitro results indicated that addition to the culture medium of ursolic acid (p < 0.01 for 500 microM) resulted in a reduction of glutamate-oxalate-transaminase, lactate dehydrogenase activities and in a good survival rate for the CCl4-intoxicated hepatocytes. Ursolic acid also ameliorated lipid peroxidation in primary cultured rat hepatocytes exposed to CCl4, as demonstrated by a reduction in malondialdehyde production. Moreover, ursolic acid (50-500 microM) showed radical scavenging properties in terms of hydroxyl formation. The results obtained suggest that ursolic acid treatment can normalize the disturbed antioxidant status of rats intoxicated with CCl4 by maintaining the levels of glutathione and by inhibiting the production of malondialdehyde due to its radical scavenging properties.

Alanine Transaminase↗
PubMed2001

Anti-inflammatory activity of abietic acid, a diterpene isolated from Pimenta racemosa var. grissea.

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.

Abietanes↗
PubMed2001

Effects of furocoumarins from Cachrys trifida on some macrophage functions.

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.

Animals↗
PubMed2001

New insights into the mechanism of action of the anti-inflammatory triterpene lupeol.

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.

Animals↗
PubMed2000

Failure of goserelin ovarian ablation in premenopausal women with breast cancer: two case reports.

OBJECTIVE: We hereby report on two patients receiving goserelin due to breast cancer in whom a failure in ovarian ablation was detected. A review of the hormonal effects of LHRH analogues is performed. CASE REPORTS: CASE 1: A 36-year-old female was diagnosed with breast carcinoma and treated with surgery, chemotherapy, radiotherapy, and goserelin. A 16-week gestation was detected after 17 months of uninterrumpted hormonal therapy at ablative doses. CASE 2: A 41-year-old female was diagnosed with breast carcinoma and treated with surgery, chemotherapy, radiotherapy, and tamoxifen. Goserelin was substituted for tamoxifen due to bone metastases and, 2 years later, a failure in ovarian ablation was confirmed after the reappearance of the patient's menses. CONCLUSIONS: Goserelin-induced ovarian ablation may fail after the use of appropriate doses of this drug. We suggest a possible mechanism of hormone resistance induced by the long-term administration of LHRH analogues. No fetal damage was detected after goserelin exposure in the first 4 months of gestation.

Adult↗
PubMed2000

Immunomodulating properties of the diterpene andalusol.

Andalusol [ent-13(16),14-labdadiene-6 alpha,8 alpha,18-triol], a labdane diterpene isolated from an anti-inflammatory extract of the medicinal plant Sideritis foetens Clem. was evaluated for immunomodulating properties. It exhibited a dose-dependent inhibitory effect on the hemolytic activity of the classical complement pathway and also inhibited lymphocyte proliferation induced by concanavalin A at non-cytotoxic concentrations (1-100 microM). No effect on the alternative pathway was observed. These results indicate that andalusol has immunosuppressive effects in vitro in addition to its anti-inflammatory activity.

Adjuvants, Immunologic↗
PubMed2000

[Soluble Fas in acute rejection in patients with liver transplantation. Response to treatment].

UNLABELLED: It has been suggested that in the cellular rejection of hepatic graft, the lesion provoked by cytotoxic T-lymphocytes might be mediated by the Fas antigen/Fas ligand system, producing cell death by apoptosis. AIM: To determine whether soluble Fas (sFas) is increased during treatment and to evaluate response to treatment. MATERIAL AND METHODS: Fourteen patients with orthotopic liver transplantation who presented an episode of acute cellular rejection were studied. Serum levels of sFas were detected by enzyme-immunoanalysis at diagnosis and again 5 days after treatment was completed. As control groups, sFas was analyzed in 12 patients with liver transplantation without rejection and in 10 healthy subjects. RESULTS: sFas levels were found to be significantly higher in patients with rejection than in those without rejection and in healthy subjects (24.2 +/- 39.1 vs. 2.8 +/- 4.0 vs. 0.6 +/- 1.5 UI/ml; p = 0.03). In patients with acute cellular rejection, immunosuppressive treatment significantly decreased sFas levels compared with basal values (24.2 +/- 39.1 vs. 9.9 +/- 30.2 UI/ml; p = 0.005). A clear correlation between the serum levels of sFas, glutamate oxaloacetate transaminase (GOT), glutamate-pyruvate transaminase/glutamic-pyruvic transaminase (GPT) and gamma-glutamyl transferase (GGT). CONCLUSIONS: a) The increase of sFas during rejection and the decrease in patients with a good evolution suggests that the Fas system may play an important role in the hepatocyte lesion produced by an apoptosis mechanism in these patients. b) Monitoring sFas could be useful in diagnosing rejection and in evaluating response to treatment.

Acute Disease↗
PubMed1999

Inhibition of NOS-2 expression in macrophages through the inactivation of NF-kappaB by andalusol.

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.

Animals↗
PubMed1999

Hepatitis G virus infection as a possible causative agent of community-acquired hepatitis and associated aplastic anaemia.

Aplastic anaemia complicating hepatitis is a rare but well-documented phenomenon; however in many patients the cause remains unknown. We present a 24-year-old man with a well-defined community-acquired hepatitis, probably due to hepatitis G virus (HGV), who developed severe aplastic anaemia. In this case, the absence of other agents likely to cause the clinical manifestations, and the detection of HGV RNA at the time of illness, clearly point to this agent as being responsible for both the hepatitis and the aplastic anaemia. Further studies in serial serum samples and meticulous evaluation of the disorders associated with the infection will be needed to prove or dispute a causal association of HGV and aplastic anaemia.

Adult↗
PubMed1998

Antiinflammatory and antioxidant activity of plants used in traditional medicine in Ecuador.

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.

Animals↗
PubMed1997

Viral replication in patients with concomitant hepatitis B and C virus infections.

The aim of this study was to assess the implications of dual infection with hepatitis B virus (HBV) and hepatitis C virus (HCV). The HBV and HCV status in 100 patients with chronic hepatitis was analysed. HBV DNA was studied using liquid hybridization and the polymerase chain reaction (PCR). HCV viremia was measured using qualitative and quantitative PCR. The HCV genotype was determined by PCR. Patients were divided into three groups according to their HCV-RNA and HBsAg status: group I consisted of 40 patients with chronic hepatitis caused by HBV; group II, 40 patients with chronic hepatitis caused by HCV; and group III, 20 patients infected with both viruses. The HBV-DNA level was higher in group I than in group III (66.4 vs. 11.5 pg/ml; p < 0.05). Quantification of HCV viremia revealed mean values of 36.9 copies x 10(5)/ml in group II and 5.5 copies/ml x 10(5) in group III (p < 0.05). The mean aminotransferase level and histological activity were higher in group III. HCV genotype lb was the predominant type. The data suggest that there is reciprocal inhibition of viral replication in patients with dual HBV and HCV infection. Liver disease appears to be more severe in patients with chronic hepatitis B and C.

Adolescent↗
PubMed1996

A novel diterpenoid labdane from Sideritis javalambrensis inhibits eicosanoid generation from stimulated macrophages but enhances arachidonate release.

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.

Animals↗