Kaurane and pimarane-type diterpenes from the Viguiera species inhibit vascular smooth muscle contractility.

The research, development and use of natural products as therapeutic agents, especially those derived from plants, have been increasing in recent years. Despite the fact that plants provide a rich source of novel biologically active compounds, only a small percentage have been phytochemically investigated and studied for their medical potential. Viguiera is a genus that belongs to the family Asteraceae and to the sunflower tribe Heliantheae, which is widespread mostly in Mexico and in other areas of the Andes and upland areas of Brazil.

The decrease of NAD(P)H has a prominent role in dopamine toxicity.

We characterized dopamine toxicity in human neuroblastoma SH-SY5Y cells as a direct effect of dopamine on cell reductive power, measured as NADH and NADPH cell content. In cell incubations with 100 or 500 microM dopamine, the accumulation of dopamine inside the cell reached a maximum after 6 h. The decrease in cell viability was 40% and 75%, respectively, after 24 h, and was not altered by MAO inhibition with tranylcypromine.

Pharmacological comparison of the vasorelaxant action displayed by kaurenoic acid and pimaradienoic acid.

The vascular effects of two natural occurring diterpenes from the kaurane and pimarane classes were compared. The diterpenes ent-kaur-16-en-19-oic acid (kaurenoic acid; KA) and ent-pimara-8(14), 15-dien-19-oic acid (pimaradienoic acid; PA) were tested for their antispasmodic activity on isolated rat aorta. Vascular reactivity experiments, using standard muscle bath procedures, showed that KA and PA (both at 50 and 100 microM) inhibited phenylephrine and KCl-induced contraction in both endothelium-intact and endothelium-denuded rat aortic rings, with PA being more effective than KA.

Inhibition of the growth of premalignant and malignant human oral cell lines by extracts and components of black raspberries.

Black raspberries are a rich natural source of chemopreventive phytochemicals. Recent studies have shown that freeze-dried black raspberries inhibit the development of oral, esophageal, and colon cancer in rodents, and extracts of black raspberries inhibit benzo(a)pyrene-induced cell transformation of hamster embryo fibroblasts. However, the molecular mechanisms and the active components responsible for black raspberry chemoprevention are unclear.

[Clinical study on the pharmacological treatment of hemorrhoids with 0.25% oxethacaine chlorhydrate].

In this clinical study, the authors refer to a thirty-six month treatment of Grades I and II haemorrhoids (pharmacological treatment) with a group of 75 patients (45 females and 30 males) and treatment for Grades III and IV haemorrhoids (Pharmacological and surgical treatment) on a second group of 23 patients for a total of 98 patients treated and observed. For the pharmacological treatment, a rectal cream containing 0.25% Oxethacaine chlorhydrate (Emoren, produced by Novasorel, srl) was used on all patients.

Role of the carboxylic group in the antispasmodic and vasorelaxant action displayed by kaurenoic acid.

The present work describes the investigation of the role of the carboxylic group in the structure-activity relationship of the diterpene ent-kaur-16-en-19-oic acid (kaurenoic acid, KA) in inhibiting rat aorta contraction. For this purpose the methylation of the C-19 carboxyl group of KA was carried out. The effects of the obtained ent-methyl-kaur-16-en-19-oate (KAMe) were compared with those induced by KA.

BMP-2 decreases Mash1 stability by increasing Id1 expression.

In neural development, bone morphogenetic proteins (BMPs) restrict neuronal differentiation, thereby promoting the maintenance of progenitor cells or even inducing astrocytogenesis. We report that exposure of neuroendocrine lung carcinoma cells to BMP-2 leads to a rapid decline in steady-state levels of Mash1 protein and some neuron-specific markers. BMP-2 induces a post-transcriptional decrease in Mash1 levels through enhanced degradation.

Abnormal alpha-synuclein interactions with rab3a and rabphilin in diffuse Lewy body disease.

The present study examines alpha-synuclein interactions with rab3a and rabphilin by antibody arrays, immunoprecipitation and pull-down methods in the entorhinal cortex of control cases and in diffuse Lewy body disease (LBD) cases. Alpha-synuclein immunoprecipitation revealed alpha-synuclein binding to rabphilin in control but not in LB cases. Immunoprecipitation with rab3a disclosed rab3a binding to rabphilin in control but not in LB cases.

Analysis of the mechanisms underlying the vasorelaxant action of kaurenoic acid in the isolated rat aorta.

The present work describes the mechanisms involved in the vasorelaxant effect of the diterpene ent-kaur-16-en-19-oic acid (kaurenoic acid). Kaurenoic acid (10, 50 and 100 microM) concentration-dependently inhibited phenylephrine and KCl-induced contraction in either endothelium-intact or -denuded rat aortic rings. Kaurenoic acid also reduced CaCl(2)-induced contraction in Ca(2+)-free solution containing KCl (30 mM).

Abnormal alpha-synuclein interactions with Rab proteins in alpha-synuclein A30P transgenic mice.

Mutation A30P in the alpha-synuclein gene is a cause of familial Parkinson disease. Transgenic mice expressing wild mouse and mutant human A30P alpha-synuclein, Tg5093 mice (Tg), show a progressive motor disorder characterized by tremor, rigidity, and dystonia, accompanied by accumulation of alpha-synuclein in the soma and neurites and by a conspicuous gliosis beginning in the hippocampal formation at the age of 7 to 8 months and spreading throughout the CNS. Impaired short-term changes in synaptic strength have also been documented in hippocampal slices from Tg mice.

Prevention of recurrent upper respiratory tract infections in a community of cloistered nuns using a new immunostimulating bacterial lysate. A randomized, double-blind clinical trial.

Unlabelled: The aim of the present study was to evaluate the efficacy of the immunostimulating therapy with a new vaccine Ismigen in preventing recurrent infections of the upper respiratory tract in subjects belonging to a community of cloistered nuns. This product is a lysate obtained by mechanical lysis of bacteria (MLBL) usually responsible of respiratory tract infections. A randomized, double-blind, parallel groups, placebo controlled clinical trial was carried out in 47 nuns (age range 25-80 years) living in a cloistered religious community, suffering from recurrent infections of the upper respiratory tract.

Evidence for the mechanisms underlying the effects of pimaradienoic acid isolated from the roots of Viguiera arenaria on rat aorta.

The present study examines the effects of the diterpene ENT-pimara-8(14),15-dien-19-oic acid (PA) on rat thoracic aorta. PA (10(-5), 3 x 10(-5) and 10(-4) mol/l) caused concentration-dependent inhibition of phenylephrine (Phe)-induced contraction in either endothelium-intact or endothelium-denuded aortic rings. PA attenuated the contraction induced by CaCl(2) in Ca(2+)-free solution containing Phe (10(-7) mol/l) or KCl (30 mmol/l).

Decolorization of reactive azo dyes by Cunninghamella elegans UCP 542 under co-metabolic conditions.

The inappropriate disposal of dyes in wastewater constitutes an environmental problem and can cause damage to the ecosystem. Alternative treatments have been reported that fungi are particularly effective in the decolorization of textile effluents. The decolorization of dyes with different molecular structures by Cunninghamella elegans was evaluated under several media conditions.

Neuroprotective effect of citicoline in 6-hydroxydopamine-lesioned rats and in 6-hydroxydopamine-treated SH-SY5Y human neuroblastoma cells.

Citicoline (CDP-choline or cytidine 5'-diphosphocholine) has been used as a therapeutic agent in combination with levodopa in the treatment of Parkinson's disease (PD). The present study examines the effects of citicoline by using validated in vivo and in vitro models. Citicoline reduces the cytotoxic effect of 6-hydroxydopamine (6-OHDA)-treated human dopaminergic SH-SY5Y neuroblastoma cells as measured cellular redox activity with 3-[4.

Piroxicam selectively inhibits the growth of premalignant and malignant human oral cell lines by limiting their progression through the S phase and reducing the levels of cyclins and AP-1.

Studies have shown that nonsteroidal antiinflammatory drugs (NSAIDs) reduce the risk of and mortality from a variety of cancers. Although cyclooxygenase (COX)-dependent and -independent pathways may be involved, the mechanisms responsible for these effects remain unknown. In our study, we found that piroxicam inhibited cell growth in premalignant and malignant, but not normal, human oral epithelial cell lines in a concentration- and time-dependent manner.

Dopamine induces autophagic cell death and alpha-synuclein increase in human neuroblastoma SH-SY5Y cells.

Free cytoplasmic dopamine may be involved in the genesis of neuronal degeneration in Parkinson's disease and other such diseases. We used SH-SY5Y human neuroblastoma cells to study the effect of dopamine on cell death, activation of stress-induced pathways, and expression of alpha-synuclein, the characteristic protein accumulated in Lewy bodies. We show that 100 and 500 microM dopamine causes a 40% and 60% decrease of viability, respectively, and triggers autophagy after 24 hr of exposure, characterized by the presence of numerous cytoplasmic vacuoles with inclusions.

TGF-beta1 increases tyrosine hydroxylase expression by a mechanism blocked by BMP-2 in human neuroblastoma SH-SY5Y cells.

Human neuroblastoma SH-SY5Y cells were used to study the effects of transforming growth factor beta1 (TGF-beta1) and bone morphogenetic protein 2 (BMP-2) on neuronal differentiation and acquisition of a catecholaminergic phenotype. SH-SY5Y cells express the intracellular factors activated through the receptors of the TGFbeta superfamily members, Smad1 and Smad4, as in basal conditions or after differentiation with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or retinoic acid (RA). TGF-beta1 and BMP-2 induce differentiation in SH-SY5Y cells by different pathways: the effect of TGF-beta1 is potentiated by TPA and the effect of BMP-2 is blocked by RA.

Dosing sequence-dependent pharmacokinetic interaction of oxaliplatin with paclitaxel in the rat.

Background: In a phase I clinical trial of oxaliplatin (OPT) in combination with paclitaxel (PXL), a pharmacokinetic interaction was observed when OPT was given as a 2-h i.v. infusion followed by a 1-h i.

Citicoline increases glutathione redox ratio and reduces caspase-3 activation and cell death in staurosporine-treated SH-SY5Y human neuroblastoma cells.

Citicoline, or CDP-choline, is an essential endogenous intermediate in the biosynthesis of phosphatidylcholine that may act as a neuroprotector in several models of neurodegeneration. The present study analyses the effects of citicoline in the paradigm of staurosporine-induced cell death in human SH-SY5Y neuroblastoma cells. Citicoline reduces apoptosis induced by 100 nM staurosporine for 12 h in SH-SY5Y cells.

Pimarane diterpene from Viguiera arenaria (Asteraceae) inhibit rat carotid contraction.

ent-Pimara-8(14),15-dien-19-oic acid (PA) isolated from Viguiera arenaria (Asteraceae; Heliantheae) inhibited rat carotid rings contraction induced by phenylephrine (10(-8) mol/l) or potassium chloride (45 mmol/l) at concentration ranging from 5 to 20 microg/ml. This inhibitory effect was not reversible after the removal of this compound from the medium bath.

Neuroprotective effect of the monoamine oxidase inhibitor PF 9601N [N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine] on rat nigral neurons after 6-hydroxydopamine-striatal lesion.

Monoamine oxidase B (MAO-B) inhibitors are potentially useful in the therapeutic treatment of Parkinson's disease. L-Deprenyl has been shown to slow nigrostriatal tract degeneration in human idiopathic Parkinsonism and to be an effective neuroprotector in experimental 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity models. However, L-amphetamine and (-)methamphetamine, the metabolites generated by L-deprenyl, can have adverse and severe side-effects.

MPP+ increases alpha-synuclein expression and ERK/MAP-kinase phosphorylation in human neuroblastoma SH-SY5Y cells.

Alpha-synuclein is a brain presynaptic protein that is linked to familiar early onset Parkinson's disease and it is also a major component of Lewy bodies in sporadic Parkinson's disease and other neurodegenerative disorders. Alpha-synuclein expression increases in substantia nigra of both MPTP-treated rodents and non-human primates, used as animal models of parkinsonism. Here we describe an increase in alpha-synuclein expression in a human neuroblastoma cell line, SH-SY5Y, caused by 5-100 microM MPP+, the active metabolite of MPTP, which induces apoptosis in SH-SY5Y cells after a 4-day treatment.

Pharmacokinetics of oxaliplatin (NSC 266046) alone and in combination with paclitaxel in cancer patients.

Unlabelled: Oxaliplatin (OPT), a third-generation platinating agent, is currently being evaluated in a phase II clinical trial in head and neck cancer patients and in a phase I clinical trial in combination with paclitaxel (TXL).

Purpose: The aim of this study was to investigate the pharmacokinetics and biological correlates of OPT alone as well as the potential pharmacokinetic interaction between OPT and TXL.

Methods: In the phase II study, OPT was given alone as a 2-h i.