A diferenciação sexual cerebral é um fenômeno importante que ocorre no período perinatal essencial para definir alguns padrões comportamentais na orientação sexual na fase adulta. Este evento ocorre após uma descarga abrupta da testosterona testicular no recém-nascido que é convertido em estrógeno E2 pela aromatase no hipotálamo do neonato e, juntamente com aquela de origem materna promove as alterações no cérebro que determinam a orientação sexual masculina do neonato. Em fêmeas, o E organiza o cérebro feminino e a orientação sexual. Assim, investigou-se o efeito do Citrato de Clomifeno, um inibidor da aromatase em ratos machos e fêmeas tratados perinatalmente. Os resultados mostraram alterações comportamentais e bioquímicas compatíveis com a desmasculinização, alteração do comportamento sexual de ambos os sexos, comportamento homossexual, ciclo estral, alteração dos níveis de testosterona, estrógeno, FSH e LH e do peso dos órgãos na fase adulta. Os resultados são explicados pelo bloqueio da aromatase, no período da diferenciação sexual cerebral. / Sexual differentiation of the brain is an important phenomenon that occurs perinatally essential to define some behavioral patterns of sexual orientation in adulthood. This event occurs after an abrupt discharge of testicular testosterone in newborns that E2 is converted into estrogen by aromatase in the hypothalamus of the newborn and, along with that of maternal origin promotes changes in the brain that determine sexual orientation male neonate. In females, the E organizes the female brain and sexual orientation. Thus, we investigated the effect of clomiphene citrate, aromatase inhibitor in male and female rats treated perinatally. The results showed behavioral and biochemical changes consistent with demasculinization, altered sexual behavior of both sexes, homosexual behavior, estrous cycle, changing levels of testosterone, estrogen, FSH and LH and organ weight in adulthood. The results are explained by blocking the aromatase during the period of sexual differentiation of the brain.

Orientador: Renée Laufer Amorim / Resumo: O glaucoma é a principal causa global de cegueira irreversível e o número de pessoas com glaucoma em todo o mundo aumentará para 111,8 milhões em 2040, mesmo com os tratamentos vigentes. Deste modo, enseja uma necessidade de desenvolver terapias neuroprotetoras que possam ser usadas para reduzir os efeitos perniciosos do glaucoma, como a morte de células ganglionares da retina (CGR). Avanços na compreensão da fisiopatologia do glaucoma é um fator chave na compreensão da patogênese da neuropatia glaucomatosa. Neste contexto a isquemia retiniana desempenha um papel central em várias doenças da retina. A patogênese da isquemia retiniana envolve alterações temporais da morfologia e morfometria da retina assim como mudanças na expressão gênica e protéica. O Citrato de Sildenafila (SC) mostrou efeito protetor nos modelos de isquemia/reperfusão (I/R) com efeitos neuroprotetores. Contudo, a administração oral de CS, em humanos, encontra inúmeros efeitos colaterais, tais como redução da pressão arterial, dores de cabeça, rubor e congestão nasal são concomitantes, assim como pacientes com moderada a grave doença cardiovascular ou aqueles submetidos a terapia a base de nitrato apresentam riscos secundários aumentados para efeitos cardiovasculares adversos. Deste modo, propomos que a administração tópica de CS pode ser uma alternativa à via oral e também ser igualmente neuroprotetor no glaucoma e podem minimizar os riscos indesejados no uso sistêmico desse fármaco, além de oferecer uma n... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Glaucoma is the leading global cause of irreversible blindness and the number of people with glaucoma worldwide will increase to 111.8 million by 2040, even with current treatments. Thus, there is a need to develop neuroprotective therapies that can be used to reduce the deleterious effects of glaucoma, such as retinal ganglion cell death (RBC). Advances in understanding the pathophysiology of glaucoma are a key factor in understanding the pathogenesis of glaucomatous neuropathy. In this context, retinal ischemia plays a central role in various diseases of the retina. The pathogenesis of retinal ischemia involves temporal changes in retinal morphology and morphometry as well as changes in gene and protein expression. Sildenafil Citrate (SC) showed protective effect in the ischemia / reperfusion (I / R) models with neuroprotective effects. However, oral administration of CS in humans finds numerous side effects such as reduced blood pressure, headaches, flushing and nasal congestion are concomitant, as well as patients with moderate to severe cardiovascular disease or those undergoing nitrate therapy have increased secondary risks for adverse cardiovascular effects. Thus, we propose that the eye drops administration of CS may be an alternative to the oral route and also be equally neuroprotective in glaucoma and may minimize the undesirable risks in the systemic use of this drug, as well as offer a new approach for the therapeutic intervention in the pathogenesis of neuropathy... (Complete abstract click electronic access below) / Doutor

Orientador: Renée Laufer Amorim / Resumo: O glaucoma é a principal causa global de cegueira irreversível e o número de pessoas com glaucoma em todo o mundo aumentará para 111,8 milhões em 2040, mesmo com os tratamentos vigentes. Deste modo, enseja uma necessidade de desenvolver terapias neuroprotetoras que possam ser usadas para reduzir os efeitos perniciosos do glaucoma, como a morte de células ganglionares da retina (CGR). Avanços na compreensão da fisiopatologia do glaucoma é um fator chave na compreensão da patogênese da neuropatia glaucomatosa. Neste contexto a isquemia retiniana desempenha um papel central em várias doenças da retina. A patogênese da isquemia retiniana envolve alterações temporais da morfologia e morfometria da retina assim como mudanças na expressão gênica e protéica. O Citrato de Sildenafila (SC) mostrou efeito protetor nos modelos de isquemia/reperfusão (I/R) com efeitos neuroprotetores. Contudo, a administração oral de CS, em humanos, encontra inúmeros efeitos colaterais, tais como redução da pressão arterial, dores de cabeça, rubor e congestão nasal são concomitantes, / Abstract: Glaucoma is the leading global cause of irreversible blindness and the number of people with glaucoma worldwide will increase to 111.8 million by 2040, even with current treatments. Thus, there is a need to develop neuroprotective therapies that can be used to reduce the deleterious effects of glaucoma, such as retinal ganglion cell death (RBC). Advances in understanding the pathophysiology of glaucoma are a key factor in understanding the pathogenesis of glaucomatous neuropathy. In this context, retinal ischemia plays a central role in various diseases of the retina. The pathogenesis of retinal ischemia involves temporal changes in retinal morphology and morphometry as well as changes in gene and protein expression. Sildenafil Citrate (SC) showed protective effect in the ischemia / reperfusion (I / R) models with neuroprotective effects. However, oral administration of CS in humans finds numerous side effects such as reduced blood pressure, headaches, flushing and nasal congestion are concomitant, as well as patients with moderate to severe cardiovascular disease or those undergoing nitrate therapy have increased secondary risks for adverse cardiovascular effects. Thus, we propose that the eye drops administration of CS may be an alternative to the oral route and also be equally neuroprotective in glaucoma and may minimize the undesirable risks in the systemic use of this drug, as well as offer a new approach for the therapeutic intervention in the pathogenesis of neuropathy... (Complete abstract click electronic access below) / Doutor

A diferenciação sexual cerebral é um fenômeno importante que ocorre no período perinatal essencial para definir alguns padrões comportamentais na orientação sexual na fase adulta. Este evento ocorre após uma descarga abrupta da testosterona testicular no recém-nascido que é convertido em estrógeno E2 pela aromatase no hipotálamo do neonato e, juntamente com aquela de origem materna promove as alterações no cérebro que determinam a orientação sexual masculina do neonato. Em fêmeas, o E organiza o cérebro feminino e a orientação sexual. Assim, investigou-se o efeito do Citrato de Clomifeno, um inibidor da aromatase em ratos machos e fêmeas tratados perinatalmente. Os resultados mostraram alterações comportamentais e bioquímicas compatíveis com a desmasculinização, alteração do comportamento sexual de ambos os sexos, comportamento homossexual, ciclo estral, alteração dos níveis de testosterona, estrógeno, FSH e LH e do peso dos órgãos na fase adulta. Os resultados são explicados pelo bloqueio da aromatase, no período da diferenciação sexual cerebral. / Sexual differentiation of the brain is an important phenomenon that occurs perinatally essential to define some behavioral patterns of sexual orientation in adulthood. This event occurs after an abrupt discharge of testicular testosterone in newborns that E2 is converted into estrogen by aromatase in the hypothalamus of the newborn and, along with that of maternal origin promotes changes in the brain that determine sexual orientation male neonate. In females, the E organizes the female brain and sexual orientation. Thus, we investigated the effect of clomiphene citrate, aromatase inhibitor in male and female rats treated perinatally. The results showed behavioral and biochemical changes consistent with demasculinization, altered sexual behavior of both sexes, homosexual behavior, estrous cycle, changing levels of testosterone, estrogen, FSH and LH and organ weight in adulthood. The results are explained by blocking the aromatase during the period of sexual differentiation of the brain.

Rockfish are commercially and recreationally important, yet due to the in habitat depths at which rockfish inhabit, little is known about their ecology. As a consequence, management of rockfish population as a fishery resource is a work in progress. In particular, changes in physiological condition aver the course of the year is poorly described. This study examined 19 different species of Sebastes from the Southern California Bight over four seasons (late summer, fall, winter, and spring) using metabolic enzyme assays. Enzymes used were lactate dehydrogenase (LDH), malate dehydrogenase (MDH), pyruvate kinase (PK), and citrate synthase (CS). Some muscle composition data (percent water, percent protein, percent lipid, and protein as a percentage of wet mass) were also used to help interpret the enzyme data. Enzyme activity was lowest in the summer when expressed as activity per gram wet weight but when it was expressed per gram protein the trend was reversed. We found that the rockfish tend to have the highest protein as a percentage of wet mass (P%WM) in the spring right before the upwelling period begins and have the lowest P%WM in late summer after the peak of upwelling. Their metabolic poise (represented as CS/LDH) grouped according to locomotory habit (benthic or bentho-pelagic). A mass and oxygen consumption plot also showed that the species group according to locomotory habit. With those known to be benthic grouped together and those species that are known to more actively swimming had higher values. This knowledge could be used to infer whether a rockfish that hasn't been well studied is benthic or bentho-pelagic.

This work deals with the search for new molybdate-type catalyst formulations for the activation of light alkanes and their conversion to alkenes. In the first part, we showed that is possible to stabilize the beta-phase of NiMoO4 (as pure phase) by incorporating a certain amount of Co in its lattice. The sol-gel method was also applied to the synthesis of solid solutions of NiMoO4 and CoMoO4. The main difference between the bulk and silica-dispersed Ni-Co-Mo catalysts prepared by citrate or sol-gel methods as well as impregnation, is related to the fact that it is possible to stabilize the beta-Ni1-xCoxMoO4 phase throughout the whole composition range in the dispersed catalysts. Moreover, the catalytic data emphasize the advantage of using mixed Ni-Co molybdates in comparison with simple Ni or Co molybdates and also the fact that a higher activity is reached when these active phases are dispersed in a silica matrix. In the second part, we reported on the synthesis, characterization and catalytic activity of solid solutions of Ni and Co molybdates dispersed on different supports such as Al2O3, MgO, TiO2, ZrO2 and Al2O3-MgO. These experiments demonstrate that supporting or dispersing the mixed Ni1-xCoxMoO4 phase on any kind of support leads to the preferential stabilization of the beta-phase. It was also shown that catalysts characterized by intermediate acid-base properties give better catalytic performances than those with high acidity or high basicity. Bi and/or Ln- (La, Ce, Pr, Sm, Tb) modified Ni, Co and mixed Ni-Co molybdates were prepared, characterized and investigated from the point of view of their catalytic behaviour. The incorporation of a lanthanide in Ni and/or Co molybdate stabilizes the b-phase for citrate-prepared catalysts. Concerning the catalytic activity of these solids, a strong enhancement of the catalytic activity and the selectivity towards propene is observed when solid solutions of beta-NiMoO4 and beta-CoMoO4 are modified by a lanthanide, except in the case of Sm. The Tb-modified catalyst is the one displaying the highest propene productivity, but the most selective catalysts are those modified by La or Pr. Incorporation of Ce strongly improves the catalytic activity, more than propene selectivity. The presence of Bi in the formulation of the catalyst results in a lower propene selectivity.

Citrate-coated gadolinium trifluoride (Cit-GdF3) and poly(acrylic acid)-coated nanoparticles (PAA-GdF3 NPs) were synthesized, the former reproduced from literature (though using more refined conditions), the latter through a new, two-step, ligand exchange method. Diamagnetic nanoparticle analogs (Cit-YF3 NPs) were prepared to investigate citrate interactions with the nanoparticle surface using NMR. Citrate was found to bind in numerous conformations, with a total of between 29 – 46 % bound at 0 ºC. Exchange studies revealed short residence lifetimes of one and twelve seconds respectively for bound and free forms of citrate (0 ºC), perhaps explaining the colloidal instability of these nanoparticles. PAA-GdF3 NPs were synthesized by first producing their Cit-GdF3 counterparts, and then exchanging citrate for PAA. The impetus behind this latter synthesis was the relative enhancement in stability and relaxivity attainable by these nanoparticles. The displacement of citrate by PAA was verified using diffusion NMR studies.

Citrate-coated gadolinium trifluoride (Cit-GdF3) and poly(acrylic acid)-coated nanoparticles (PAA-GdF3 NPs) were synthesized, the former reproduced from literature (though using more refined conditions), the latter through a new, two-step, ligand exchange method. Diamagnetic nanoparticle analogs (Cit-YF3 NPs) were prepared to investigate citrate interactions with the nanoparticle surface using NMR. Citrate was found to bind in numerous conformations, with a total of between 29 – 46 % bound at 0 ºC. Exchange studies revealed short residence lifetimes of one and twelve seconds respectively for bound and free forms of citrate (0 ºC), perhaps explaining the colloidal instability of these nanoparticles. PAA-GdF3 NPs were synthesized by first producing their Cit-GdF3 counterparts, and then exchanging citrate for PAA. The impetus behind this latter synthesis was the relative enhancement in stability and relaxivity attainable by these nanoparticles. The displacement of citrate by PAA was verified using diffusion NMR studies.

No description available.

In this study first time, we have cloned and sequenced the citrate synthase gene from a thermoacidophilic archaeon Thermoplasma (Tp.) volcanium (Optimum growth temperature of Tp.volcanium is 60oC and optimum pH is 2.0.). For cloning we have followed a PCR based approach. Amplification of citrate synthase gene from chromosomal DNA of Tp.volcanium yielded a product of 1476 bp containing an open reading frame of 1161 bp comprising the structural gene. After ligation of the PCR amplicon to pDrive vector through AU complementation, recombinant plasmids were transferred into E.coli TG-1 competent cells. Out of three recombinants, E.coli pDriveCS-31 was selected for further characterization by restriction mapping and DNA sequencing. Southern Blotting and Hybridization using the membrane blot of pDriveCS-31 plasmid and DIG-labeled PCR amplified citrate synthase gene probe, also confirmed the cloning of Tp.volcanium citrate synthase gene in E.coli. Clustal W Version 1.82 was used for alignment of aminoacid sequence of Tp.volcanium citrate synthase with that of other archaeal, bacterial and eukaryotic citrate synthases. The highest sequence similarity (87%) was found between Tp.volcanium and Tp.acidophilum enzymes. Despite low sequence homology (18%) with the pig enzyme, of the 11 residues implicated in catalytic activity of the pig citrate synthase 9 were conserved in the Tp.volcanium enzyme. Heterologous expression of this citrate synthase gene in E.coli has been achieved under the control of its promoter sequences. The recombinant enzyme (386 aa) has been purified to homogeneity by affinity chromatography on Reactive Red 120 column. The subunit molecular size was estimated as 43 kDa. The purified enzyme followed classical Michaelis-Menten kinetics. The Km values of 5.15 &amp / #956 / M and 5.60 &amp / #956 / M, and Vmax values of 1.74 &amp / #956 / moles/ml/min and 1.60 &amp / #956 / moles/ml/min were calculated from Lineweaver-Burk plots for acetyl-CoA and oxaloacetate, respectively. The recombinant enzyme was thermostable and retained about 80% of the activity at 85oC after 1 hour.