Antibacterial activity of the essential oil from Lippia aff. gracillis.

The essential oil of fresh leaves of Lippia aff. gracillis was analyzed by GC/MS and evaluated for its antibacterial effects. The results showed a moderate antibacterial activity and confirm the traditional uses of L. aff. gracillis.

Synthesis and biological activity of novel acridinylidene and benzylidene thiazolidinediones.

A novel set of acridinylidene thiazolidinediones and benzylidene thiazolidinediones was synthesized by nucleophilic addition of cyanoacrylates. Some of these compounds were evaluated for their glucose lowering capability and their effects on the triglyceride level in alloxan diabetic mice.

Evaluation of Gilles de la Tourette syndrome with [99mTc] HMPAO Brain SPECT

Gilles de la Tourette syndrome (GLTS) is a disorder characterized by tics and several behavioral disturbances. Although GLTS is a relatively common disorder, little is known about its pathophysiology. Previous studies with SPECT and PET were performed in a small number of patients and have shown some discordant data. The aim of this study is to evaluate brain perfusion abnormalities in patients with GLTS and to correlate them with the clinical manifestations of the syndrome. Twenty-eight patients were submitted to brain [99mTc]-HMPAO SPECT. 82 percent of the patients had abnormal studies. The most frequent finding was perfusion abnormalities in the thalami in 16 patients (57 percent) and 85 percent of patients with hyperperfusion of one or both thalami had complex motor tics. This investigation has demonstrated that brain perfusion SPECT is able to identify cortical perfusion abnormalities, associated with clinical symptoms in patients with GLTS. These abnormalities involve the pre-frontal-striatal-thalamic-cortical pathways

Enhanced inhibition of HIV-1 replication in macrophages by antisense oligonucleotides, ribozymes and acyclic nucleoside phosphonate analogs delivered in pH-sensitive liposomes.

An antisense oligodeoxynucleotide against the human immunodeficiency virus type 1 (HIV-1) Rev response element, a ribozyme complementary to the HIV-1 5'-LTR, and the reverse transcriptase inhibitors 9-(2-phosphonylmethoxyethyl) adenine (PMEA) and (R)-9-(2-phosphonylmethoxypropyl)-adenine (PMPA) inhibited virus replication in monocyte-derived macrophages more effectively when delivered in pH-sensitive liposomes compared to the free drugs.

Liposome-mediated delivery of antiviral agents to human immunodeficiency virus-infected cells.

Intracellular delivery of novel macromolecular drugs against human immunodeficiency virus type-1 (HIV-1), including antisense oligodeoxynucleotides, ribozymes and therapeutic genes, may be achieved by encapsulation in or association with certain types of liposomes. Liposomes may also protect these drugs against nucleases. Low-molecular-weight, charged antiviral drugs may also be delivered more efficiently via liposomes. Liposomes were targeted to HIV-1-infected cells via covalently coupled soluble CD4. An HIV-1 protease inhibitor encapsulated in conventional negatively charged multilamellar liposomes was about 10-fold more effective and had a lower EC90 than the free drug in inhibiting HIV-1 production in human monocyte-derived macrophages. The drug encapsulated in sterically stabilized liposomes was as effective as the free drug. The EC50 of the reverse transcriptase inhibitor 9-(2-phosphonylmethoxyethyl)adenine (PMEA) was reduced by an order of magnitude when delivered to HIV-1-infected macrophages in pH-sensitive liposomes. A 15-mer antisense oligodeoxynucleotide against the Rev response element was ineffective in free form against HIV-1 replication in macrophages, while delivery of the oligonucleotide in pH-sensitive liposomes inhibited virus replication. The oligodeoxynucleotide encapsulated in sterically stabilized pH-sensitive liposomes with prolonged circulation in vivo, which were recently developed in the laboratories of the authors, was also highly effective. A ribozyme complementary to HIV-1 5'-LTR delivered in pH-sensitive liposomes inhibited virus production by 90%, while the free ribozyme caused only a slight inhibition. Cationic liposome-mediated co-transfection of the HIV-regulated diphtheria toxin A fragment gene and a proviral HIV clone into HeLa cells completely inhibited virus production, while the frame-shifted mutant gene was ineffective. Co-transfection of the proviral genome and a gene encoding a Rev-binding aptamer into HeLa cells via transferrin-associated cationic liposomes inhibited virus production. These studies indicate that liposomes can be used to facilitate the intracellular delivery of certain anti-HIV agents and to enhance their therapeutic effects. These properties may be particularly advantageous in the development of novel macromolecular drugs, which may be necessary because of the emergence of virus strains resistant to the currently available drugs.

Anti-allergic properties of the natural PAF antagonist yangambin.

In this study we examined the ability of the furofuran lignan yangambin to influence the local and systemic responses induced by antigen or PAF in actively sensitized or normal rats. Given intraperitoneally 1 h before stimulation, yangambin inhibited the pleural neutrophil and eosinophil infiltration evoked by the i.pl. injection of PAF or antigen into normal or 14 daysensitized rats whereas plasma exudation evoked by both stimuli was unaffected. The pleural neutrophil influx (6 h) after LTB4 stimulation was also significantly inhibited by yangambin. We also evidenced that the hemoconcentration, thrombocytopenia, and leucocytosis noted after i.v. PAF were all attenuated by yangambin. In actively sensitized rats, pretreatment with yangambin failed to modify the antigen-induced hemoconcentration and leucocytosis, but dose-dependently abrogated the thrombocytopenia noted 1 h post-stimulation. In vitro, the anaphylactic contraction of longitudinal jejunal segments to antigen challenge was significantly inhibited by yangambin (10(-5)-10(-4) M). Likewise, the contraction of jejunal segments from normal rats to PAF was markedly blocked by yangambin under conditions where the response to 5-hydroxytryptamine (5-HT) was not altered. In conclusion, our results show that antigen- and PAF-induced pleural neutrophil and eosinophil accumulation, but not exudation, is sensitive to treatment with yangambin. In addition, yangambin also suppressed the pleural neutrophil infiltration triggered by LTB4 as well as the blood thrombocytopenia and intestinal anaphylaxis elicited by antigen in rats. Thus, our findings indicate that yangambin shows an antagonistic action on receptors other than those of PAF, i.e., LTB4, and strongly suggest that it may be a useful drug in the treatment of some allergic inflammatory responses.

Vitamin A activity of buriti (Mauritia vinifera Mart) and its effectiveness in the treatment and prevention of xerophthalmia.

The fruit of buriti, a palm tree that grows wild in some regions of Brazil, contains beta-carotene in its oily fraction in a concentration 10 times higher than that of red-palm oil. The effectiveness of buriti sweet in the treatment and prevention of xerophthalmia was tested in 44 children aged 43-144 mo through daily supplementation with an amount corresponding to 134 micrograms retinol equivalent over 20 d. The results demonstrated that this natural food source of vitamin A can reverse clinical xerophthalmia and restore liver reserves of the vitamin, suggesting its possible utilization in intervention programs to combat vitamin A deficiency in countries where the fruit is available or has the potential for cultivation.