Brazilian green propolis on Helicobacter pylori infection. a pilot clinical study

Recent in vitro studies suggest that propolis and some of its phenolic components are able to inhibit Helicobacter pylori growth. To date, there are no clinical studies. AIMS: To evaluate the effect of Brazilian green propolis on H. pylori-infected individuals. PATIENTS AND METHODS: Eighteen (11 females, 7 males, mean age 47 years) participants were included. Before treatment, all participants were submitted to gastroscopy, and H. pylori infection was confirmed by histology, urease test, and (13)C-urea breath test (UBT). Participants with UBT showing a delta over baseline (DOB) value higher than 4 per thousand were considered positive for H. pylori infection. Twenty drops from an alcoholic preparation of Brazilian green propolis were administered three times a day for 7 days. Clinical evaluation and UBT were performed at 1-3 days and at 40 days after the end of therapy to evaluate H. pylori suppression or eradication, respectively. RESULTS: All participants took all medication and completed the study. Eighty-three percent of the subjects did not succeed in suppressing or eradicating H. pylori. Two participants reached partial suppression after treatment, but became positive again at UBT performed 40 days after treatment. Another participant presented negative at UBT 40 days after treatment, not confirmed by a second UBT performed 100 days after treatment. CONCLUSIONS: Brazilian green propolis used in popular dose showed minimal effect on H. pylori infection. Larger studies with longer duration, larger dose, and different frequency of administration of propolis extract should be undertaken to define its role on H. pylori therapy.     

Leishmania amazonensis: biosynthesis of polyprenols of 9 isoprene units by amastigotes

The isoprenoid metabolic pathway in protozoa of the Leishmania genus exhibits distinctive characteristics. These parasites, as well as other members of the Trypanosomatidae family, synthesize ergosterol, instead of cholesterol, as the main membrane sterol lipid. Leishmania has been shown to utilize leucine, instead of acetate as the main precursor for sterol biosynthesis. While mammalian dolichols are molecules containing 15-23 isoprene units, Leishmania amazonensis promastigotes synthesize dolichol of 11 and 12 units. In this paper, we show that the intracellular stages of L. amazonensis, amastigotes, synthesize mainly polyprenols of 9 isoprene units, instead of dolichol.     

The non-competitive AMPA receptor antagonist (GYKI 52466) blocks quisqualate-induced acetylcholine release from the rat hippocampus and striatum: an in vivo microdialysis study

The effects of the non-N-methyl-D-aspartate (NMDA) agonist quisqualate (QUIS) and selective AMPA/kainate receptor antagonist 1-(aminophenyl)-methyl-7, 8-methyilendioxy-5H-2,3-benzodiazepine (GYKI 52466) on the release of acetylcholine (ACh) from the hippocampus and striatum of freely moving rats were studied by transversal microdialysis. Acetylcholine level in the dialisate was measured by the high performance liquid chromatography (HPLC) method with an electrochemical detector. The QUIS (100 microM) perfused through the striatum induced an increase of extracellular ACh level (250%) which lasted for over 1h and gradually returned to basal values. Local perfusion of GYKI 52466 (10-100 microM) to the striatum did not change the basal release of ACh. GYKI 52466 (10 microM) administered together with QUIS (100 microM) in he striatum antagonized the stimulant effect of QUIS on the ACh release.Local administration of the QUIS (100 microM) through the microdialysis fiber implanted in the hippocampus, caused a long lasting increase of extracellular hippocampal ACh level (360%) which was reversed when the drug was withdrawn from the perfusion solution. The stimulant effect of QUIS was antagonized by concomitant perfusion of GYKI (10 microM). No effect was seen on the basal ACh release when GYKI (10-100 microM) was perfused through the hippocampus.Local perfusion with tetrodotoxin (1 microM) decrease the basal release of ACh and prevented the QUIS-induced increase of ACh both in the hippocampus and striatum.Our in vivo neurochemical results indicate that hippocampal and striatal cholinergic systems are regulated by non-NMDA (probably AMPA) glutamatergic receptors located in the hippocampus and striatum.     

Synthesis, structure and cytotoxic activity of mixed-valent Cu(I)/Cu(II) salt containing a pyrazolone derivative as ligand

The compound [Cu(TAMEN)][Cu(NCS)₂Cl](DMF)₂ containing the Mannich base N,N′-tetra-(4-antipyrylmethyl)-1,2-diaminoethane (TAMEN), as ligand, was synthesized and characterized by conductometric, magnetic, electronic and infrared spectroscopic properties. The single-crystal X-ray structure shows the presence of two well defined complex units, [Cu(TAMEN)]²⁺ and [Cu(NCS)₂Cl]²⁻.The complex cation contains copper(II) in the elongated pseudo-octahedral environment created by the N₂O₄ donor set of TAMEN whereas, the counterion exhibits a pseudo trigonal planar geometry around the Cu(I) ion.Both, the pyrazolonic ligand and the complex have been screened for their cytotoxic activity against human tumor cell lines: glioblastoma multiforme, breast cancer, hepatoma and lung carcinoma. The nontumor cell lines MDBK (bovine kidney) and BALB/c 3T3 clone 31 (mouse embryo) were also included in the experiments. In contrast to the ligand TAMEN, the [Cu(TAMEN)][Cu(NCS)₂Cl](DMF)₂ was found to decrease in a time- and concentration-dependent manner the viability of cultured tumor (MCF-7, A549, 8MGBA, Hep G2) and non-tumor (MDBK, BALB/c 3T3) cell lines.     

Behavior of natural estrogens in semicontinuous activated sludge biodegradation reactors

Biological degradation of natural estrogens was investigated by separately spiking 17 beta-estradiol (E2) and estrone (E1) into activated sludge reactors operated in a semi-continuous flow mode under aerobic conditions. By conducting runs for simultaneous addition of glucose over the designated initial concentrations of 0, 10, 30, 50 and 100 mg l(-1), respectively, the likely effect of the easily biodegradable organic constituent on the degradation rate of the natural estrogens was also studied. The spiked E2 disappeared in a manner much faster than E1; and its disappearance occurred through elimination of its metabolic byproduct of E1. The apparent first-order disappearance rate of E2 and E1 fell in the ranges of 0.84-4.31h(-1) and 0.15-0.84 h(-1), respectively when spiked separately into respective reactors. A general trend of decreases in the disappearance rate with increases of the initial glucose concentration was revealed. The presence of glucose was also found capable of lowering the conversion ratio from E2 to E1.     

The effect of vasoactive intestinal polypeptide (VIP) on the canine gallbladder motility.

1. VIP at doses of 10(-9) to 10(-8) M was ineffective and at doses of 5 x 10(-8) to 10(-7) M exerted a slight inhibitory effect on the tone of the canine gallbladder muscle strip. However, VIP (0.1-1 micrograms/kg) injected intravenously (i.v.) in conscious dogs dose-dependently decreased the gallbladder pressure. 2. VIP did not influence significantly the acetylcholine (ACh)- or carbachol- induced contractions of canine gallbladder under in vitro or in vivo conditions, but it decreased the electrically-induced, atropine-sensitive contractions of gallbladder muscle strips. 3. VIP (5 x 10(-9) to 5 x 10(-8) M) did not influence significantly the dose-response curve for cholecystokinin octapeptide (CCK OP) of canine and guinea-pig gallbladder muscle strips. VIP injected i.v. (0.1-0.5 micrograms/kg) in conscious dogs greatly decreased the CCK OP-induced gallbladder pressure.     

Activin,a Grape Seed-derived Proanthocyanidin Extract,Reduces Plasma Levels of Oxidative Stress and Adhesion Molecules (ICAM-1, VCAM-1 and E-selectin) in Systemic Sclerosis

This study evaluated whether a new generation antioxidant Activin derived from the grape seed proanthocyanidins, could reduce the induction of the adhesion molecules as a result of inflammatory response in the plasma of systemic sclerosis (SSc) patients. SSc patients were divided into two groups: one group was treated with Activin, a grape seed‐derived proanthocyanidins, while the other group served as control. Patients were given Activin 100 mg/day orally for one month after which the blood samples were withdrawn from both groups of the patients. Blood was also taken from normal human volunteers. Plasma was obtained in fasting state between 8 to 9 A.M. from two groups of SSc patients and controls. Soluble adhesion molecules including ICAM‐1, VCAM‐1, E‐selectin and P‐selectin as well as malonaldehyde, a marker for oxidative stress, were measured. The results of our study demonstrated up‐regulation of these soluble adhesion molecules except for P‐selectin, in the plasma of the SSc patients compared to those obtained from human volunteers. Activin significantly attenuated the increased expression of these adhesion molecules. In addition, there was a significant increase in the amount of malondialdehyde formation in the plasma of the SSc patients, which was also attenuated by Activin. The results of this study demonstrated that Activin could reduce the inflammatory response and the oxidative stress developed in SSc patients.     

Synthesis, characterization and evaluation of antileishmanial activity of copper(II) with fluorinated α-hydroxycarboxylate ligands

In this study, Cu(II) complexes with fluorinated ligands were produced aiming at the development of new, less toxic antileishmanial metallodrugs. Complexes of the general formula CuL₂ (L = lactate, trifluorolactate, 2-hydroxyisobutyrate, trifluoro-2-hydroxyisobutyrate) were synthesized in methanolic medium, purified by crystallization and characterized by elemental analysis and electronic and infrared spectroscopies. In vitro experiments with Leishmania amazonensis promastigotes showed that the trifluorolactate derivative more active than its non-fluorinated counterpart. Our results indicate that fluorinated chelators may be interesting to increase metal toxicity and/or open new paths for metallodrug chemotherapy against leishmaniasis.     

Somatostatin stimulates striatal acetylcholine release by glutamatergic receptors: an in vivo microdialysis study

The modulation of striatal cholinergic neurons by somatostatin (SOM) was studied by measuring the release of acetylcholine (ACh) in the striatum of freely moving rats. The samples were collected via a transversal microdialysis probe. ACh level in the dialysate was measured by the high performance liquid chromatography method with an electrochemical detector. Local administration of SOM (0.1, 0.5 and 1 microM) produced a long-lasting and concentration-dependent increase in the basal striatal ACh output. The stimulant effect of SOM was antagonized by the SOM receptor antagonist cyclo(7-aminopentanoyl-Phe-D-Trp-Lys-Thr[BZL]) (1 microM). In a series of experiments, we studied the effect of 6,7-dinitroquinoxaline-2, 3-dione (DNQX), a selective non-NMDA (N-methyl-D-aspartate) glutamatergic antagonist, on the basal and SOM-induced ACh release from the striatum. DNQX, 2 microM, perfused through the striatum had no effect on the basal ACh output but inhibited the SOM (1 microM)-induced ACh release. The non-NMDA glutamatergic receptor antagonist 1-(4-aminophenyl)-4-methyl-7,8-methylendioxy-5H-2,3- benzodiazepine (GYKI-52466), 10 microM, antagonized the SOM (1 microM)-induced release of ACh in the striatum. Local administration of the NMDA glutamatergic receptor antagonist, 2-amino-5-phosphonopentanoic acid (APV), 100 microM, blocked SOM (1 microM)-evoked ACh release. Local infusion of tetrodotoxin (1 microM) decreased the basal release of ACh and abolished the 1 microM SOM-induced increase in ACh output suggesting that the stimulated release of ACh depends on neuronal firing. The present results are the first to demonstrate a neuromodulatory role of SOM in the regulation of cholinergic neuronal activity of the striatum of freely moving rats. The potentiating effect of SOM on ACh release in the striatum is mediated (i) by SOM receptor located on glutamatergic nerve terminals, and (ii) by NMDA and non-NMDA glutamatergic receptors located on dendrites of cholinergic interneurones of the striatum.