ABSTRACT
RATIONALE: Schizophrenic patients show perceptual deficits, which may be detected in visual illusion tasks. Previous studies found that chronic patients show increased sensitivity to Müller-Lyer illusion as the disorder progresses, although there are a few conflicting reports in the scientific literature. To address these issues, moderate and chronic schizophrenic patients were tested on the Brentano version of the Müller-Lyer illusion task. Their performance was compared to first-degree relatives and unrelated matched controls. Chronic patients showed increased susceptibility to the illusion. Performance on the visual illusion task was not correlated to the number of years since disease onset, medication or (Positive and Negative Syndrome Scale) PANSS scores. The lack of association between illusion sensitivity and PANSS score may reflect the absence of the perceptual dimension in this scale. Based on these results, we suggest that susceptibility to the Müller-Lyer illusion is associated with the stage of schizophrenia rather than disease length.
Subject(s)
Illusions , Optical Illusions , Schizophrenia , HumansABSTRACT
Alzheimer's disease (AD) is a progressive neurodegenerative disease that deeply affects patients, their family and society. Although scientists have made intense efforts in seeking the cure for AD, no drug available today is able to stop AD progression. In this context, compounds isolated from animal venom are potentially successful drugs for neuroprotection, since they selectively bind to nervous system targets. In this review, we presented different studies using peptides isolated from animal venom for the treatment of AD. This is a growing field that will be very helpful in understanding and even curing neurodegenerative diseases, especially AD.
Subject(s)
Alzheimer Disease/drug therapy , Amyloid beta-Peptides/metabolism , Memory/physiology , Peptides/therapeutic use , Venoms/metabolism , Alzheimer Disease/metabolism , Animals , Disease Progression , HumansABSTRACT
The development of biocompatible polymeric nanoparticles has become an important strategy for optimizing the therapeutic efficacy of many classical drugs, as it may expand their activities, reduce their toxicity, increase their bioactivity and improve biodistribution. In this study, nanoparticles of Amphotericin B entrapped within poly (lactic-co-glycolic) acid and incorporated with dimercaptosuccinic acid (NANO-D-AMB) as a target molecule were evaluated for their physic-chemical characteristics, pharmacokinetics, biocompatibility and antifungal activity. We found high plasma concentrations of Amphotericin B upon treatment with NANO-D-AMB and a high uptake of nanoparticles in the lungs, liver and spleen. NANO-D-AMB exhibited antifungal efficacy against Paracoccidioides brasiliensis and induced much lower cytotoxicity levels compared to D-AMB formulation in vivo and in vitro. Together, these results confirm that NANO-D-AMB improves Amphotericin B delivery and suggest this delivery system as a potential alternative to the use of Amphotericin B sodium deoxycholate.
Subject(s)
Amphotericin B/chemistry , Amphotericin B/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Deoxycholic Acid/chemistry , Deoxycholic Acid/pharmacology , Drug Carriers/chemistry , Lactic Acid/chemistry , Nanoparticles/chemistry , Polyglycolic Acid/chemistry , Amphotericin B/adverse effects , Amphotericin B/therapeutic use , Animals , Antifungal Agents/adverse effects , Antifungal Agents/therapeutic use , Deoxycholic Acid/adverse effects , Deoxycholic Acid/therapeutic use , Drug Carriers/pharmacokinetics , Drug Combinations , Drug Liberation , Lactic Acid/pharmacokinetics , Materials Testing , Mice , Paracoccidioides/drug effects , Paracoccidioides/physiology , Paracoccidioidomycosis/drug therapy , Polyglycolic Acid/pharmacokinetics , Polylactic Acid-Polyglycolic Acid Copolymer , Safety , Succimer/chemistry , Tissue DistributionABSTRACT
BACKGROUND AND PURPOSE: In this work, a neuroactive peptide from the venom of the neotropical wasp Polybia occidentalis was isolated and its anti-nociceptive effects were characterized in well-established pain induction models. EXPERIMENTAL APPROACH: Wasp venom was analysed by reverse-phase HPLC and fractions screened for anti-nociceptive activity. The structure of the most active fraction was identified by electron-spray mass spectrometry (ESI-MS/MS) and it was further assessed in two tests of anti-nociceptive activity in rats: the hot plate and tail flick tests. KEY RESULTS: The most active fraction contained a peptide whose structure was Arg-Pro-Pro-Gly-Phe-Thr-Pro-Phe-Arg-OH, which corresponds to that of Thr(6)-BK, a bradykinin analogue. This peptide was given by i.c.v. injection to rats. In the tail flick test, Thr(6)-BK induced anti-nociceptive effects, approximately twice as potent as either morphine or bradykinin also given i.c.v. The anti-nociceptive activity of Thr(6)-BK peaked at 30 min after injection and persisted for 2 h, longer than bradykinin. The primary mode of action of Thr(6)-BK involved the activation of B(2) bradykinin receptors, as anti-nociceptive effects of Thr(6)-BK were antagonized by a selective B(2) receptor antagonist. CONCLUSIONS AND IMPLICATIONS: Our data indicate that Thr(6)-BK acts through B(2) bradykinin receptors in the mammalian CNS, evoking antinociceptive behaviour. This activity is remarkably different from that of bradykinin, despite the structural similarities between both peptides. In addition, due to the increased metabolic stability of Thr(6)-BK, relative to that of bradykinin, this peptide could provide a novel tool in the investigation of kinin pathways involved with pain.
