La presente tesis "Las multitudes políticas de Lima y Callao de 1912 y la elección de Billinghurst" para optar el grado de Doctor en Historia, mereció larga dedicación desde que apareció como inquietud por investigar el gobierno y la administración de dicho mandatario (1912-1914), pero por la magnitud y alcances de la misma hubo que reformularla y orientarla a una propuesta de caracterización de aquél período: el populismo temprano y urbano, el primero del siglo y, tal vez el segundo en aparecer en la Historia del Perú.

Text in Afrikaans / After taking her severely incapacitated husband to Europe immediately after the cessation of hostilities to obtain specialist medical treatment, Mrs Rachel Isabella Steyn (Tibbie) in 1905 brought the partially recovered Pres Steyn back to South Africa. She joined forces with her husband to revive the defeated Afrikaner socially, spiritually and materially. Tibbie assisted her husband with establishing the Oranje School for Girls in 1906, and in 1907 the Oranje Association for Women (OVV) was formed with Tibbie as chairperson. Although she was English speaking by birth, she openly identified herself with efforts to promote Afrikaans as a cultural language. Alongside her husband she worked for the building of the National Women's Monument to commemorate those who had died during the war. During all these activities she conscientiously cared for the health and spiritual needs of Pres Steyn. After Pres Steyn's death in 1916 she emerged more forcefully in public life. After the First World War in co-operation with Emily Hobhouse she collected money for the needy in Central Europe. She was constantly occupied with alleviating the needs of people, e.g. by collecting small donations from her people who had been impoverished by the war. In this manner a home could be acquired for Emily Hobhouse and Mrs De Wet, widow of the famous war general, could be assisted in her need. In 1926 Tibbie also arranged the burial of Emily Hobhouse at the Women's Monument. As a leader among her people Tibbie experienced the tensions of the Rebellion and two world wars without becoming involved publicly. Despite sharp political differences between the two language groups and amongst members of her own fam~ly, she successfully maintained her role as binding force. She preferred acting behind the scenes. She was the patroness of many organisations, and while she was often involved in ceremonial situations she always performed her duties with grace. Among both English and Afrikaans speaking peoples she was held in high esteem and among Afrikaners she spontaneously became accepted as Volksmoeder. When she was 83 years of age the Government asked her to act as South Africa's official representative at the abdication of Queen Wilhelmina of the Netherlands. She was accorded a state funeral at the Women's Monument when she died on 3 January 1955. / Nadat sy haar ernstig ongestelde man na die einde van die Anglo-Boereoorlog vir gespesialiseerde mediese behandeling na Europa geneem het, het mev. Rachel Isabella Steyn (Tibbie) die gedeeltelik herstelde pres. M. T. Steyn in 1905 na Suid-Afrika terug gebring. Sy het haar saam met pres. Steyn beywer om die verslane Afrikanervolk op maatskaplike, geestelike en stoflike gebied weer op te hef. Tibbie het pres. Steyn bygestaan met die oprigting van die Meisieskool Oranje in 1906. In 1907 het die stigting van die Oranje-Vrouevereniging (OVV) onder haar voorsitsterskap geskied. Hoewel sy van afkoms Engelssprekend was, was sy een van die eerstes wat Afrikaans tot skryftaal verhef het. Aan die sy van haar eggenoot het sy gewerk vir die oprigting van die Nasionale Vrouemonument om die gestorwe vroue en kinders van die oorlog te gedenk. Te midde van dit alles het sy nougeset gewaak oor pres. Steyn se gesondheid en sy geestelike welsyn. Na pres. Steyn se dood in 1916 tree sy sterker na vore in die openbare lewe. In samewerking met Emily Hobhouse samel sy na die Eerste Wereldoorlog geld in vir noodlydendes van Sentraal-Europa. Sy het haar voortdurend beywer vir die verligting van die lot van haar mense, o.a. met die insameling van halfkrone by 'n oorlogsverarmde volk. So is o.a. 'n huis vir Emily Hobhouse bekom, en is die nood van genl. De Wet se weduwee verlig. Tibbie het ook in 1926 die leiding geneem met die begrafnis van Emily Hobhouse by die Vrouemonument. As leiersfiguur het sy die spanning van die Rebellie en die twee wereldoorloe sonder enige omstredenheid deurleef. Te midde van skerp politieke verskille tussen die taalgroepe en onder haar eie familie tree sy met sukses as saambindende krag op. Hoewel sy geweldige invloed gehad het, het sy by voorkeur agter die skerms opgetree. Sy was beskermvrou van verskeie organisasies en waar sy dikwels by seremoniele geleenthede betrek was, het sy haar pligte met groot grasie vervul. Onder sowel Engelse as Afrikaners is sy sonder voorbehoud geeer, en by die Afrikaners het sy spontaan die eretitel van Volksmoeder verwerf. Op drie-en-tagtigjarige ouderdom is sy in 1948 deur die Regering afgevaardig as Suid-Afrika se gesant tydens die plegtighede verbonde aan die abdikasie van koningin Wilhelmina van Nederland. Sy is 'n staatsbegrafnis by die Vrouemonument gegee toe sy op 3 Januarie 1955 oorlede is. / History / D. Litt. et Phil. (Geskiedenis)

Hormone-dependent cancers (HDCs), such as those of the prostate, ovary, breast and endometrium, share characteristics that indicate similar underlying mechanisms of carcinogenesis. Through steroid hormone signalling on "down-stream" target genes, the growth, development and progression of HDCs are regulated. One such family of target genes, highly expressed in HDCs and regulated by steroid hormones, are the tissue kallikreins (KLKs). The KLKs are a multigene family of serine proteases involved in physiological processes such as blood pressure regulation, inflammation, and tumour development and progression via the hydrolysis of specific substrates. Although the KLK gene family is clearly implicated in tumourigenesis, the precise roles played by these genes are largely unknown. Additionally, except for the androgen-responsive genes, KLK2 and KLK3, the mechanisms underlying their hormonal regulation in HDCs are yet to be identified. The initial focus of this thesis was to examine the regulation of the kallikreins, KLK1 and KLK4, by estradiol and progesterone in endometrial and breast cancer cell lines. From these studies, progesterone clearly regulated KLK4 expression in T47D cells and therefore, the focus of the remaining studies was to further examine this regulation at the transcriptional level. An overview of the results obtained is detailed below. Human K1 and hK4 protein levels were increased by 10 nmol/L estradiol benzoate, progesterone, or a combination of the two, over 48 hours in the endometrial cancer cell line, KLE. However, these same treatments resulted in no change in KLK1 gene or hK1 protein levels in the endometrial cancer cell lines, HEC1A or HEC1B (only hK1 analysed). Progesterone treatment (0-100 nmol/L) over 24 hours resulted in a clear increase in KLK4 mRNA at the 10 nmol/L dose in the breast cancer cell line, T47D. Additionally, treatment of T47D cells with 10 nmol/L progesterone over 0-48 hr, resulted in the rapid expression of the hK4 protein at 2 hr which was sustained for 24 hr. Further analysis of this latter progesterone regulation with the antiprogesterone, RU486, over 24 hours, resulted in an observable decrease in hK4 levels at 1 µmol/L RU486. Although the estrogen and progesterone regulation of the hK1 protein was not further analysed, the data obtained for hK4 regulation in T47D cell lines, supported the premise that this gene was progesterone-responsive. The rapid expression of hK4 protein by progesterone at two hours suggests that KLK4 transcription is directly coupled to progesterone regulation, perhaps through progesterone receptor (PR) binding to progesterone-responsive regions within the KLK4 promoter or far "up-stream" regions. Thus, the following further studies were performed. To test this hypothesis, the transcription initiation site (TIS) and 5' flanking regions of the KLK4 gene in T47D cells were interrogated. Primer extension and 5' RACE identified the TIS 78 bp 5' of the putative ATG site for translation as identified by Korkmaz et al. (2001). This KLK4 gene transcript consists of only four exons, and thus excludes the pre/pro signal peptide. Although a TATA-box is not present within -25 to -30 bp 5' of the identified TIS, a number of consensus binding motifs for Sp1 and estrogen receptor half-sites were identified. It is possible that the Sp1 sites are involved in the basal levels of transcription for this gene. Additionally, a putative progesterone response element (PRE) was identified in the far "up-stream" regions of the KLK4 gene. Basal levels of transcription were observed within the KLK4 proximal promoter region when coupled to a luciferase reporter gene and transfected into T47D cell lines. Additionally, the KLK4 proximal promoter region did not induce the luciferase reporter gene expression when progesterone was added to the system, however, estradiol was inhibitory for luciferase gene expression. This suggests that the proximal promoter region of the KLK4 gene could contain functional EREs but not PREs. In keeping with this hypothesis, some ER half-sites were identified, but PR sites were not obvious within this region. The identified PRE in the far "up-stream" region of the KLK4 gene assembled the progesterone receptor in vitro, and in vivo, as assessed by electromobility shift assays and chromatin immunoprecipitation assays (EMSAs and ChIPs), respectively. The binding of the PR to the KLK4 PRE was successfully competed out by a PR antibody and not by an androgen receptor antibody, and thus confirms the specificity of the KLK4 PRE-PR complex. Additionally, the PR was recruited and assembled onto and off the progesterone-responsive KLK4 region in a cyclic fashion. Thus, these data strongly suggest that the PR represents one of the core components of a transcription complex for the KLK4 gene, and presumably also contributes to the expression of this gene. Moreover, these data suggest a functional coordination between the PR and the KLK4 progesterone-responsive region in T47D cells, and thus, provide a model system to further study these events in vivo.

Text in Afrikaans / After taking her severely incapacitated husband to Europe immediately after the cessation of hostilities to obtain specialist medical treatment, Mrs Rachel Isabella Steyn (Tibbie) in 1905 brought the partially recovered Pres Steyn back to South Africa. She joined forces with her husband to revive the defeated Afrikaner socially, spiritually and materially. Tibbie assisted her husband with establishing the Oranje School for Girls in 1906, and in 1907 the Oranje Association for Women (OVV) was formed with Tibbie as chairperson. Although she was English speaking by birth, she openly identified herself with efforts to promote Afrikaans as a cultural language. Alongside her husband she worked for the building of the National Women's Monument to commemorate those who had died during the war. During all these activities she conscientiously cared for the health and spiritual needs of Pres Steyn. After Pres Steyn's death in 1916 she emerged more forcefully in public life. After the First World War in co-operation with Emily Hobhouse she collected money for the needy in Central Europe. She was constantly occupied with alleviating the needs of people, e.g. by collecting small donations from her people who had been impoverished by the war. In this manner a home could be acquired for Emily Hobhouse and Mrs De Wet, widow of the famous war general, could be assisted in her need. In 1926 Tibbie also arranged the burial of Emily Hobhouse at the Women's Monument. As a leader among her people Tibbie experienced the tensions of the Rebellion and two world wars without becoming involved publicly. Despite sharp political differences between the two language groups and amongst members of her own fam~ly, she successfully maintained her role as binding force. She preferred acting behind the scenes. She was the patroness of many organisations, and while she was often involved in ceremonial situations she always performed her duties with grace. Among both English and Afrikaans speaking peoples she was held in high esteem and among Afrikaners she spontaneously became accepted as Volksmoeder. When she was 83 years of age the Government asked her to act as South Africa's official representative at the abdication of Queen Wilhelmina of the Netherlands. She was accorded a state funeral at the Women's Monument when she died on 3 January 1955. / Nadat sy haar ernstig ongestelde man na die einde van die Anglo-Boereoorlog vir gespesialiseerde mediese behandeling na Europa geneem het, het mev. Rachel Isabella Steyn (Tibbie) die gedeeltelik herstelde pres. M. T. Steyn in 1905 na Suid-Afrika terug gebring. Sy het haar saam met pres. Steyn beywer om die verslane Afrikanervolk op maatskaplike, geestelike en stoflike gebied weer op te hef. Tibbie het pres. Steyn bygestaan met die oprigting van die Meisieskool Oranje in 1906. In 1907 het die stigting van die Oranje-Vrouevereniging (OVV) onder haar voorsitsterskap geskied. Hoewel sy van afkoms Engelssprekend was, was sy een van die eerstes wat Afrikaans tot skryftaal verhef het. Aan die sy van haar eggenoot het sy gewerk vir die oprigting van die Nasionale Vrouemonument om die gestorwe vroue en kinders van die oorlog te gedenk. Te midde van dit alles het sy nougeset gewaak oor pres. Steyn se gesondheid en sy geestelike welsyn. Na pres. Steyn se dood in 1916 tree sy sterker na vore in die openbare lewe. In samewerking met Emily Hobhouse samel sy na die Eerste Wereldoorlog geld in vir noodlydendes van Sentraal-Europa. Sy het haar voortdurend beywer vir die verligting van die lot van haar mense, o.a. met die insameling van halfkrone by 'n oorlogsverarmde volk. So is o.a. 'n huis vir Emily Hobhouse bekom, en is die nood van genl. De Wet se weduwee verlig. Tibbie het ook in 1926 die leiding geneem met die begrafnis van Emily Hobhouse by die Vrouemonument. As leiersfiguur het sy die spanning van die Rebellie en die twee wereldoorloe sonder enige omstredenheid deurleef. Te midde van skerp politieke verskille tussen die taalgroepe en onder haar eie familie tree sy met sukses as saambindende krag op. Hoewel sy geweldige invloed gehad het, het sy by voorkeur agter die skerms opgetree. Sy was beskermvrou van verskeie organisasies en waar sy dikwels by seremoniele geleenthede betrek was, het sy haar pligte met groot grasie vervul. Onder sowel Engelse as Afrikaners is sy sonder voorbehoud geeer, en by die Afrikaners het sy spontaan die eretitel van Volksmoeder verwerf. Op drie-en-tagtigjarige ouderdom is sy in 1948 deur die Regering afgevaardig as Suid-Afrika se gesant tydens die plegtighede verbonde aan die abdikasie van koningin Wilhelmina van Nederland. Sy is 'n staatsbegrafnis by die Vrouemonument gegee toe sy op 3 Januarie 1955 oorlede is. / History / D. Litt. et Phil. (Geskiedenis)

Les maladies cardiovasculaires sont la principale cause de décès dans le monde. Actuellement, leur prévalence croît en Afrique subsaharienne où l'hypertension représente un facteur de risque cardiovasculaire majeur. Différents médicaments sont utilisés pour le traitement de l'hypertension mais dans les pays à revenu faible en général, et en R.D.Congo en particulier, le niveau socio-économique bas de la population pousse cette dernière à faire appel à la médecine traditionnelle. En R.D.Congo, les tradithérapeutes utilisent une multitude de plantes pour traiter l’hypertension. Cependant, les propriétés pharmacologiques de certaines de ces plantes sur la fonctionnalité vasculaire n’ont pas encore été étudiées de manière approfondie.<p>Afin de donner une base scientifique à l’utilisation de ces plantes dans le traitement de l'hypertension artérielle en médecine traditionnelle congolaise, nous avons réalisé dans un premier temps une enquête ethnobotanique. Celle-ci a été menée auprès de tradipraticiens de Kinshasa et du Bas-Congo, dans l'ouest de la R.D.Congo, afin d'obtenir des informations spécifiques sur les plantes qui sont utilisées pour traiter l'hypertension. Suite à cette enquête, trois plantes ont été sélectionnées :les feuilles et les écorces de racines de Combretum racemosum P. Beauv (Combretaceae), les feuilles de Combretum celastroides subsp. laxiflorum Welw (Combretaceae) et les écorces de tronc et de racines d'Hymenocardia acida Tul. (Euphorbiaceae). L'évaluation de l'effet vasorelaxant des extraits polaires issus de ces plantes sur les anneaux d’aorte isolée de rat a montré que les extraits testés ont un effet vasorelaxant endothélium-dépendant. Tous les extraits induisent cet effet via la voie du NO-GMPc alors que ceux de feuilles et d'écorces de racines de Combretum racemosum agissent également via la voie des prostanoïdes. Ces extraits ont aussi une action antioxydante. Enfin, l'administration chronique des extraits polaires de feuilles de Combretum celastroides subsp. laxiflorum et d'écorces de racines d'Hymenocardia acida aux rats spontanément hypertendus a montré que ces deux extraits possèdent une activité antihypertensive. Dans le but de déterminer les composés phytochimiques responsables de l’activité vasorelaxante observée, les extraits polaires de feuilles de Combretum celastroides subsp. laxiflorum et d'écorces de racines d'Hymenocardia acida ont été soumis à un fractionnement sur une colonne de polyamide. Toutes les fractions obtenues ont présenté une activité antioxydante, mais l'activité vasorelaxante était concentrée dans une fraction dont l'analyse par chromatographie liquide couplée à la spectrométrie de masse après thiolyse a indiqué qu'elle était enrichie en procyanidines. En conclusion, notre étude montre l'intérêt de ces plantes dans le traitement de l'hypertension en médecine traditionnelle congolaise, intérêt qui mérite d’être confirmé par des études cliniques rigoureuses./<p><p>Cardiovascular diseases represent a major cause of death in the world. Currently, their prevalence grows in sub-Saharan Africa where hypertension represents a major cardiovascular risk factor. Different drugs are used for the treatment of hypertension, but in low-income countries in general and in the D.R.Congo in particular, low socio-economic level forces the population to frequently recourse to the traditional health systems. In D.R.Congo, the traditional healers use a variety of plants to treat hypertension, but the pharmacological properties of some of these plants on vascular function have not been investigated.<p>To provide a scientific basis for the use of these plants in the treatment of hypertension in Congolese traditional medicine, we first carried out an ethnobotanical survey among traditional healers in some districts of Kinshasa and Bas-Congo, in the west of D.R. Congo, to obtain specific information about the plants that are used as antihypertensive remedies. As a result of this investigation, three plants were selected :leaves and root bark of Combretum racemosum P. Beauv (Combretaceae), leaves of Combretum celastroides subsp. laxiflorum Welw (Combretaceae), and trunk bark and root bark of Hymenocardia acida Tul. (Euphorbiaceae). The evaluation of the vasorelaxant effect of the polar extracts from these plants on isolated rat aorta showed that all extracts have an endothelium-dependent vasorelaxant effect. All extracts induce the vasorelaxant effect through the NO-cGMP pathway while those of Combretum racemosum leaves and root bark also act via the prostanoids pathway. These extracts also showed an antioxidant activity. Chronic administration of polar extracts of Combretum celastroides subsp. laxiflorum leaves and Hymenocardia acida root bark to spontaneously hypertensive rats showed that both extracts have an antihypertensive activity. Both extracts were fractionated on a column of polyamide in order to determine the nature of the compounds responsible for the vasorelaxant activity. All fractions obtained had an antioxidant activity but the vasorelaxant activity was concentrated in one fraction. Analysis of this fraction by liquid chromatography-mass spectrometry after thiolysis indicated that it was enriched in procyanidins. In conclusion, our study shows the interest of these plants in the treatment of hypertension in Congolese traditional medicine, interest which should be confirmed by rigorous clinical studies.<p> <p> / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished