Antinociceptive properties produced by the pregnane compound velutinol A isolated from Mandevilla velutina

Velutinol A is a pregnane compound isolated from the rhizomes of the Brazilian plant Mandevilla velutina that interferes with kinin actions and possesses anti-inflammatory action. Here, we investigate the effect produced by velutinol A in different models of inflammatory nociception. The nociceptive effect caused by the intraplantar injection of phorbol myristate acetate (PMA, 50 pmol/paw) in mice was practically abolished by coadministration of velutinol A (1-10 nmol/paw). In contrast, the coadministration of velutinol A (10 nmol/paw) failed to affect the nociceptive response elicited by either bradykinin (BK, 10 nmol/paw) or prostaglandin E(2) (PGE(2), 10 nmol/paw). Of note, velutinol A (10 nmol/paw) partially inhibited the nociceptive response caused by capsaicin (1 nmol/paw). However, velutinol A (10 microM) did not significantly interfere with the specific binding sites of [(3)H]resiniferatoxin or [(3)H]BK in vitro. Our data also suggest that these effects are related with its ability to interact with kinin B(1) receptor-mediated mechanisms, as the cotreatment of mice with velutinol A (10 nmol/paw) consistently blocked the nociceptive response induced by the selective B(1) receptor agonist des-Arg(9)-BK. Finally, the persistent hyperalgesia produced by intraplantar injection of carrageenan (300 microg/paw) was completely reversed by the coadministration of velutinol A (10 nmol/paw). Collectively, the present results show that the pregnane compound velutinol A produces peripheral antinociceptive action in some models of acute and persistent inflammatory pain by interacting with kinin B(1)-receptor mediated effects. Thus, velutinol A or its derivatives could constitute an attractive molecule of interest for the development of new analgesic drugs. Additional studies are now in progress in order to further explore its precise mechanism of action on B(1) receptor pathways.     

Effects of lithium and valproate on hippocampus citrate synthase activity in an animal model of mania

Some studies suggest that mitochondrial dysfunction may be related to the pathophysiology of bipolar disorder. In this work, we evaluated the activity of citrate synthase in rats, and the effects of the treatment with mood stabilizers (lithium and valproate) on the enzyme activity. In the first experiment (reversal treatment), amphetamine or saline were administered to rats for 14 days, and between day 8 and 14, rats were treated with either lithium, valproate or saline. In the second experiment (prevention treatment), rats were pretreated with lithium, valproate or saline, and between day 8 and 14, rats were administered amphetamine or saline. In reversal and prevention models, amphetamine administration significantly inhibited citrate synthase activity in rat hippocampus. In amphetamine-pretreated animals, valproate administration reversed citrate synthase activity inhibition induced by amphetamine. In the prevention model, pretreatment with lithium prevented amphetamine-induced citrate synthase inhibition. Our results showed that amphetamine inhibited citrate synthase activity and that valproate reversed and lithium prevented the enzyme inhibition.     

Unilateral spatial neglect: a dramatic but often neglected consequence of right hemisphere damage

INTRODUCTION: Unilateral Spatial Neglect (USN) is a common consequence of right brain damage. In the most severe cases, behavioral signs of USN can last several years and compromise patients' autonomy and social rehabilitation. These clinical facts stress the need for reliable procedures of diagnosis and rehabilitation. STATE OF THE ART: The last 3 decades have witnessed an explosion of studies on USN, which raises issues related to complex cognitive activities such as mental representation, spatial attention and consciousness. USN is probably a heterogeneous syndrome, but some of its underlying mechanisms might be understood as an association of disorders of spatial attention. A bias of automatic orienting towards right-sided objects seems typical of left USN. Afterwards, patients find it difficult to disengage their attention in order to explore the rest of the visual scene. Neglected objects are sometimes processed in an "implicit" way. PERSPECTIVES: The development of behavioural paradigms and of neuroimaging techniques and their application to the study of USN has advanced our understanding of the functional mechanisms of attention and spatial awareness, as well as of their neural bases. A number of new procedures for rehabilitation have recently been proposed. CONCLUSION: The present review describes the clinical presentation of USN, its anatomical basis and some of possible accounts of different aspects of neglect behavior. Results of computer simulations and of rehabilitation techniques are also presented with implications for the functioning of normal neurocognitive systems.     

Incidence of root resorption after concussion,subluxation, lateral luxation,intrusion, and extrusion: a systematic review

Traumatic dental injuries often affect the dental hard tissues, periodontal tissues, and dental pulp. Root resorption (RR) is a significantly concerning ph     

Screening of plants from the Brazilian Atlantic Forest led to the identification of Athenaea velutina (Solanaceae) as a novel source of antimetastatic agents

Plant biodiversity is a source of potential natural products for the treatment of many diseases. One of the ways of discovering new drugs is through the cytotoxic screening of extract libraries. The present study evaluated 196 extracts prepared by maceration of Brazilian Atlantic Forest trees with organic solvents and distilled water for cytotoxic and antimetastatic activity. The MTT assay was used to screen the extract activity in MCF‐7, HepG2 and B16F10 cancer cells. The highest cytotoxic extract had antimetastatic activity, as determined in in vitro assays and melanoma murine model. The organic extract of the leaves of Athenaea velutina (EAv) significantly inhibited migration, adhesion, invasion and cell colony formation in B16F10 cells. The phenolic compounds and flavonoids in EAv were identified for the first time, using flow injection with electrospray negative ionization‐ion trap tandem mass spectrometry analysis (FIA‐ESI‐IT‐MSⁿ). EAv markedly suppressed the development of pulmonary melanomas following the intravenous injection of melanoma cells to C57BL/6 mice. Stereological analysis of the spleen cross‐sections showed enlargement of the red pulp area after EAv treatment, which indicated the activation of the haematopoietic system. The treatment of melanoma‐bearing mice with EAv did not result in liver damage. In conclusion, these findings suggest that A velutina is a source of natural products with potent antimetastatic activity.