Disciplina 4.7: monitoramento e avalia????o de pol??ticas p??blicas

Monitoramento e avalia????o de pol??ticas p??blicas: conceitua????o e tipos. O M&A em experi??ncias internacionais selecionadas. Formula????o, monitoramento e avalia????o de pol??ticas p??blicas no Brasil em contexto hist??rico. Experi??ncias de M&A de agendas estrat??gicas no Brasil no per??odo recente

Concomitant rotavirus serotypes 1 and 4 infections in a diarrhoeic child from Belém, Brazil

Concomitant serotypes 1 and 4 infections were detected in a 15-month old female child with community-acquired diarrhoea which lasted 7 days and coursed with moderate dehydration. The evidence for dual rotavirus infection was offered by the following findings: a) enzyme-linked immunosorbent assay (ELISA) positive reactions to both 1 and 4 serotypes; and b) extra-migrating bands at electro-phoresis of RNA in polyacrylamide gel (PAGE). These results suggest that children living under poor sanitation conditions are heavily exposed to rotavirus infections; in addition, the co-circulation of different serotypes in the same setting sustains the current concept that a rotavirus vaccine should be rnultivalent, in order to protect children against the four epidemiologically important rotavirus G serotypes.

4-7-19, stade Pershing, [Lawrence] Shields, Américain, à l'arrivée de la course de relais de 3000 m [des Jeux interalliés, le n°835 William C. Gray, membre du relais américain, lève le poing en signe de victoire] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 54716

4-7-19, stade Pershing, arrivée du marathon [modifié des Jeux interalliés, Jean Vermeulen coupe la ligne d'arrivée, le n°971 Armando Pagliani et le n°1280 Alphonse Van Hoey sont distancés] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 54715

4-7-19, stade Pershing, marathon [modifié des Jeux interalliés, Jean Vermeulen devant Fred Faller] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 54714

4-7-19, stade Pershing, départ du marathon [modifié des Jeux interalliés, en tête n°1103 Auguste Broos et n°973 Carlo Speroni suivi par Fred Faller, puis n°846 Clyde Stout, à sa droite Jean Vermeulen, n°730 J. H. Massey, n°1189 Thomas Sinton Hewitt, n°971 Armando Pagliani, n°1280 Alphonse Van Hoey, n°972 Antenore Negri, n°1274 Jules Holsbeeke] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 54713

4-7-19, stade Pershing, saut [en] hauteur avec élan [Carl Rice, Américain, n°873, 2ème des Jeux interalliés] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 54705

4-7-19, stade Pershing, saut [en] hauteur avec élan [Jeux interalliés] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 54706

4-7-19, stade Pershing, escrime [Jeux interalliés] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 54708

4-7-19, stade Pershing, saut [en] hauteur avec élan [Robert Lyman "Dink" Templeton sautant, et Carl Rice en attente à gauche de l'aire de saut, Jeux interalliés] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 54707

Megazol and its bioisostere 4H-1,2,4-triazole: comparing the trypanocidal, cytotoxic and genotoxic activities and their in vitro and in silico interactions with the Trypanosoma brucei nitroreductase enzyme

Megazol (7) is a 5-nitroimidazole that is highly active against Trypanosoma cruzi and Trypanosoma brucei, as well as drug-resistant forms of trypanosomiasis. Compound 7 is not used clinically due to its mutagenic and genotoxic properties, but has been largely used as a lead compound. Here, we compared the activity of 7 with its 4H-1,2,4-triazole bioisostere (8) in bloodstream forms of T. brucei and T. cruzi and evaluated their activation by T. brucei type I nitroreductase (TbNTR) enzyme. We also analysed the cytotoxic and genotoxic effects of these compounds in whole human blood using Comet and fluorescein diacetate/ethidium bromide assays. Although the only difference between 7 and 8 is the substitution of sulphur (in the thiadiazole in 7) for nitrogen (in the triazole in 8), the results indicated that 8 had poorer antiparasitic activity than 7 and was not genotoxic, whereas 7 presented this effect. The determination of Vmax indicated that although 8 was metabolised more rapidly than 7, it bounds to the TbNTR with better affinity, resulting in equivalent kcat/KM values. Docking assays of 7 and 8 performed within the active site of a homology model of the TbNTR indicating that 8 had greater affinity than 7.

The relationship between monocarboxylate transporters 1 and 4 expression in skeletal muscle and endurance performance in athletes

The purpose of this study was to examine the relationship between skeletal muscle monocarboxylate transporters 1 and 4 (MCT1 and MCT4) expression, skeletal muscle oxidative capacity and endurance performance in trained cyclists. Ten well-trained cyclists (mean +/- SD; age 24.4 +/- 2.8 years, body mass 73.2 +/- 8.3 kg, VO(2max) 58 +/- 7 ml kg(-1) min(-1)) completed three endurance performance tasks [incremental exercise test to exhaustion, 2 and 10 min time trial (TT)]. In addition, a muscle biopsy sample from the vastus lateralis muscle was analysed for MCT1 and MCT4 expression levels together with the activity of citrate synthase (CS) and 3-hydroxyacyl-CoA dehydrogenase (HAD). There was a tendency for VO(2max) and peak power output obtained in the incremental exercise test to be correlated with MCT1 (r = -0.71 to -0.74; P < 0.06), but not MCT4. The average power output (P (average)) in the 2 min TT was significantly correlated with MCT4 (r = -0.74; P < 0.05) and HAD (r = -0.92; P < 0.01). The P (average) in the 10 min TT was only correlated with CS activity (r = 0.68; P < 0.05). These results indicate the relationship between MCT1 and MCT4 as well as cycle TT performance may be influenced by the length and intensity of the task.

Beta(1)-selective agonist (-)-1-(3,4-dimethoxyphenetylamino)-3-(3,4-dihydroxy)-2-propanol [(-)-RO363] differentially interacts with key amino acids responsible for beta(1)-selective binding in resting and active states.

(-)-1-(3,4-Dimethoxyphenetylamino)-3-(3,4-dihydroxy)-2-propanol [(-)-RO363] is a highly selective beta(1)-adrenergic receptor (beta(1)AR) agonist. To study the binding site of beta(1)-selective agonist, chimeric beta(1)/beta(2)ARs and Ala-substituted beta(1)ARs were constructed. Several key residues of beta(1)AR [Leu(110) and Thr(117) in transmembrane domain (TMD) 2], and Phe(359) in TMD 7] were found to be responsible for beta(1)-selective binding of (-)-RO363, as determined by competitive binding. Based on these results, we built a three-dimensional model of the binding domain for (-)-RO363. The model indicated that TMD 2 and TMD 7 of beta(1)AR form a binding pocket; the methoxyphenyl group of N-substituent of (-)-RO363 seems to locate within the cavity surrounded by Leu(110), Thr(117), and Phe(359). The amino acids Leu(110) and Phe(359) interact with the phenyl ring of (-)-RO363, whereas Thr(117) forms hydrogen bond with the methoxy group of (-)-RO363. To examine the interaction of these residues with beta(1)AR in an active state, each of the amino acids was changed to Ala in a constitutively active (CA)-beta(1)AR mutant. The degree of decrease in the affinity of CA-beta(1)AR for (-)-RO363 was essentially the same as that of wild-type beta(1)AR when mutated at Leu(110) and Thr(117). However, the affinity was decreased in Ala-substituted mutant of Phe(359) compared with that of wild-type beta(1)AR. These results indicated that Leu(110) and Thr(117) are necessary for the initial binding of (-)-RO363 with beta(1)-selectivity, and interaction of Phe(359) with the N-substituent of (-)-RO363 in an active state is stronger than in the resting state.

Vuorineuvos Uolevi Raade 4/7 1972

Kirje 4.7.1972