PHENYLBUTANOID AND TAXANE-LIKE METABOLITES FROM NEEDLES OF TAXUS-BREVIFOLIA

The structures for brevifoliol and three baccatin VI derivatives were revised to possess the novel 11(15 --> 1)-abeotaxane tricylic skeleton based on X-ray crystallographic studies. Four more new rearranged taxane derivatives related to brevifoliol and the unusual phenylbutanoid, (-)-rhododendrol, were isolated from the needles of Taxus breuifolia. Their structures were established as 10 beta-benzoxy-5 alpha-(3'-dimethylamino-3'-phenyl)-propanoxy-1 beta-hydroxy- 7 beta,9 alpha,13 alpha-triacetoxy-11(15 --> 1)-abeotaxa-4(20),11-diene; 10 beta-benzoxy-1 beta-hydroxy-5 alpha-(3'-methylamino-3'-phenyl)- propanoxy-7 beta,9 alpha,l3 alpha-triacetoxy-11(15 --> 1)-abeotaxa-4(20),11-diene; 10 beta-benzoxy-5 alpha-cinnamoxy-1 beta-hydroxy-7 beta,9 alpha,13 alpha-triacetoxy-1 1(15 --> 1)-abeotaxa-4(20),11-diene; 10 beta-benzoxy-1 beta,5 alpha-dihydroxy-7 beta,9 alpha,13 alpha-triacetoxy-11(15 --> 1)-abeotaxa-4(20),11-diene and 2(R)-hydroxy-4-(4'-hydroxyphenyl)-butane.

Estradiol`s Salutary Effects on Keratinocytes Following Trauma-Hemorrhage Are Mediated by Estrogen Receptor (ER)-alpha and ER-beta

Although administration of 17 beta-estradiol (estrogen) following trauma-hemorrhage attenuates the elevation of cytokine production and mitogen-activated protein kinase (MAPK) activation in epidermal keratinocytes, whether the salutary effects of estrogen are mediated by estrogen receptor (ER)-alpha. or ER-beta is not known. To determine which estrogen receptor is the mediator, we subjected C3H/HeN male mice to trauma-hemorrhage (2-cm midline laparotomy and bleeding of the animals to a mean blood pressure of 35 mmHg and maintaining that pressure for 90 min) followed by resuscitation with Ringer`s lactate (four times the shed blood volume) At the middle of resuscitation we subcutaneously injected ER-alpha agonist propyl pyrazole trial (PPT; 5 mu g/kg), ER-beta agonist diarylpropionitrile (DPN; 5 mu g/kg), estrogen (50 mu g/kg), or ER antagonist ICI 182,780 (150 mu g/kg). Two hours after resuscitation, we isolated keratinocytes, stimulated them with lipopolysaccharide for 24 In (5 mu g/mL for maximum cytokine production), and measured the production of interleukin (IL)-6, IL-10, IL-12, and INF-alpha and the activation of MAPK. Keratinocyte cytokine production markedly increased and MAPK activation occurred following trauma-hemorrhage but were normalized by administration of estrogen, PPT and DPN. PPT and DPN administration were equally effective in normalizing the inflammatory response of keratinocytes, indicating that both ER-alpha. and ER-beta mediate the salutary effects of estrogen on kerotinocytes after trauma-hemorrhage.

Role of cytokines (TNF-alpha, IL-1 beta and KC) in the pathogenesis of CPT-11-induced intestinal mucositis in mice: effect of pentoxifylline and thalidomide

Introduction Irinotecan (CPT-11) is an inhibitor of DNA topoisomerase I and is clinically effective against several cancers. A major toxic effect of CPT-11 is delayed diarrhea; however, the exact mechanism by which the drug induces diarrhea has not been established. Purpose Elucidate the mechanisms of induction of delayed diarrhea and determine the effects of the cytokine production inhibitor pentoxifylline (PTX) and thalidomide (TLD) in the experimental model of intestinal mucositis, induced by CPT-11. Materials and methods Intestinal mucositis was induced in male Swiss mice by intraperitoneal administration of CPT-11 (75 mg/kg) daily for 4 days. Animals received subcutaneous PTX (1.7, 5 and 15 mg/kg) or TLD (15, 30, 60 mg/kg) or 0.5 ml of saline daily for 5 and 7 days, starting 1 day before the first CPT-11 injection. The incidence of delayed diarrhea was monitored by scores and the animals were sacrificed on the 5th and 7th experimental day for histological analysis, immunohistochemistry for TNF-alpha and assay of myeloperoxidase (MPO) activity, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and KC ELISA. Results CPT-11 caused significant diarrhea, histopathological alterations (inflammatory cell infiltration, loss of crypt architecture and villus shortening) and increased intestinal tissue MPO activity, TNF-alpha, IL-1 beta and KC level and TNF-alpha immuno-staining. PTX inhibited delayed diarrhea of mice submitted to intestinal mucositis and reduced histopathological damage, intestinal MPO activity, tissue level of TNF-alpha, IL-1 beta and KC and TNF-alpha immuno-staining. TLD significantly reduced the lesions induced by CPT-11 in intestinal mucosa, decreased MPO activity, TNF-alpha tissue level and TNF-alpha immuno-staining, but did not reduce the severity of diarrhea. Conclusion These results suggest an important role of TNF-alpha, IL-1 beta and KC in the pathogenesis of intestinal mucositis induced by CPT-11.

Biomimetic synthesis of xuxuarines E alpha and E beta: Structure revision of Rzedowskia bistriterpenoids

Reaction of pristimerin with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) resulted in a biomimetic-type coupling leading to xuxuarines E alpha and E beta and not the previously reported Rzedowskia bistriterpenoids I and II suggesting that the structures proposed for these natural products need revision. A product obtained in this reaction by an unusual Diels-Alder addition followed by retro-Diels-Alder-type elimination was characterized as pristimerin dicyanophenalenedione. Complete H-1, and C-13 NMR spectral assignments of xuxuarines Ea and Eb have been made by the application of 1D and 2D NMR techniques. (c) 2007 Elsevier Ltd. All rights reserved.

Overproduction, crystallization and preliminary X-ray characterization of Abn2, an endo-1,5-alpha-arabinanase from Bacillus subtilis.

Acta Crystallographica F64 (2008) 636-638

Measuring the effects of manipulating stimulus presentation time on sensorimotor alpha and low beta reactivity during hand movement observation

The present study addresses three methodological questions that have been ignored in previous research on EEG indices of the human mirror neuron system (hMNS), particularly in regard to autistic individuals. The first question regards how to elicit the EEG indexed hMNS during movement observation: Is hMNS activation best elicited using long stimulus presentations or multiple short repetitions? The second question regards what EEG sensorimotor frequency bands reflect sensorimotor reactivity during hand movement observation? The third question regards how widespread is the EEG reactivity over the sensorimotor cortex during movement observation? The present study explored sensorimotor alpha and low beta reactivity during hand movement versus static hand or bouncing balls observation and compared two experimental protocols (long exposure vs. multiple repetitions) in the same participants. Results using the multiple repetitions protocol indicated a greater low beta desynchronisation over the sensorimotor cortex during hand movement compared to static hand and bouncing balls observation. This result was not achieved using the long exposure protocol. Therefore, the present study suggests that the multiple repetitions protocol is a more robust protocol to use when exploring the sensorimotor reactivity induced by hand action observation. In addition, sensorimotor low beta desynchronisation was differently modulated during hand movement, static hand and bouncing balls observation (non-biological motion) while it was not the case for sensorimotor alpha and that suggest that low beta may be a more sensitive index of hMNS activation during biological motion observation. In conclusion the present study indicates that sensorimotor reactivity of low beta during hand movement observation was found to be more widespread over the sensorimotor cortex than previously thought.

NEUREGULINS 1-ALPHA AND 1-BETA ON THE REGENERATION THE PERIPHERAL NERVES

Objective: To evaluate the effect of the neuregulins 1-alpha and 1-beta on the regeneration the sciatic nerves of male adult C57BL/6J mice, using the tubulization technique. Methods: Eighteen animals were used, divided into three groups. A polyethylene prosthesis was implanted in a 4.0 mm defect of the left sciatic nerve, as follows: group 1 containing only purified collagen (Vitrogen (R)); group 2, collagen with neuregulin 1-alpha; group 3, collagen with neuregulin 1-beta. The control group consisted of six segments of right sciatic nerves. After four weeks, the animals were sacrificed. A segment from the midpoint of the nerve regenerated inside the prostheses was extracted; histological sections were standardized, and slides were made up for histomorphometric analysis. Results: the results were statistically compared using the Tukey multiple comparisons test and The Student`s t test. The animals treated with neuregulins had greater numbers of myelinized axons, with a statistically significant difference in relation to the collagen-only group. There was no statistical difference between the neuregulin 1-alpha and 1-beta groups. Conclusion: The addition of neuregulins provided a significant increase in the number of myelinized fibers.

Both alpha(1)- and beta(1)-adrenoceptors in the bed nucleus of the stria terminalis are involved in the expression of conditioned contextual fear

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Long-term inhibition of 5-alpha reductase and aromatase changes the cellular and extracellular compartments in gerbil ventral prostate at different postnatal ages

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Differential expression of aromatase, estrogen receptor alpha and 17 beta-HSD associated with the processes of total testicular regression and recrudescence in the bat Myotis nigricans (Chiroptera: Vespertilionidae)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Modulation of thyroid hormone receptors, TR alpha and TR beta, by using different doses of triiodothyronine (T3) at different times

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Both alpha(1)- and beta(1)-adrenoceptors in the bed nucleus of the stria terminalis are involved in the expression of conditioned contextual fear

BACKGROUND AND PURPOSE The bed nucleus of the stria terminalis (BNST) is a limbic structure that is involved in the expression of conditioned contextual fear. Among the numerous neural inputs to the BNST, noradrenergic synaptic terminals are prominent and some evidence suggests an activation of this noradrenergic neurotransmission in the BNST during aversive situations. Here, we have investigated the involvement of the BNST noradrenergic system in the modulation of behavioural and autonomic responses induced by conditioned contextual fear in rats. EXPERIMENTAL APPROACH Male Wistar rats with cannulae bilaterally implanted into the BNST were submitted to a 10 min conditioning session (6 footshocks, 1.5 ma/ 3 s). Twenty-four hours later freezing and autonomic responses (mean arterial pressure, heart rate and cutaneous temperature) to the conditioning box were measured for 10 min. The adrenoceptor antagonists were administered 10 min before the re-exposure to the aversive context. KEY RESULTS L-propranolol, a non-selective beta-adrenoceptor antagonist, and phentolamine, a non-selective a-adrenoceptor antagonist, reduced both freezing and autonomic responses induced by aversive context. Similar results were observed with CGP20712, a selective beta 1-adrenoceptor antagonist, and WB4101, a selective a1-antagonist, but not with ICI118,551, a selective beta 2-adrenoceptor antagonist or RX821002, a selective a2-antagonist. CONCLUSIONS AND IMPLICATIONS These findings support the idea that noradrenergic neurotransmission in the BNST via a1- and beta 1-adrenoceptors is involved in the expression of conditioned contextual fear.

Silver ion high pressure liquid chromatography provides unprecedented separation of sterols: application to the enzymatic formation of cholesta-5,8-dien-3 beta-ol.

We report that silver ion HPLC provides remarkable separations of C27 sterols differing only in the number or location of olefinic double bonds. This technique has been extended to LC-MS, analysis of purified components by GC, GC-MS, and 1H NMR, and to its use on a semipreparative scale. The application of this methodology for the demonstration of the catalysis, by rat liver microsomes, of the conversion of 7-dehydrocholesterol to cholesta-5,8-dien-3 beta-ol is also presented.