El presente trabajo de investigación se ha realizado teniendo en cuenta el Reglamento de Grados y Títulos de la Escuela de Pre Grado de la Facultad de Medicina de la Universidad Nacional Mayor de San Marcos, con la finalidad de obtener el título de Médico Cirujano. Objetivo: La investigación estuvo orientada a identificar los factores de riesgo asociados al uso de terapia de reemplazo hormonal, en mujeres posmenopáusicas que se atendieron en el Hospital Nacional Arzobispo Loayza en el período comprendido entre el 01 de Enero y el 31 de Diciembre del 2009 Muestra: La muestra seleccionada estuvo comprendida por 178 pacientes, 89 casos y 89 controles. Instrumentos: Los instrumentos empleados estuvieron conformados por una ficha de recolección de datos convenientemente elaborada para los fines de estudio, se analizó la asociación de las variables a través de la prueba del Chi cuadrado, asimismo la fuerza de asociación con OR, se consideró α: 0,05. Tipo de Estudio: Observacional. Diseño de investigación: Analítico de casos y controles, transversal y retrospectivo. Resultado: La investigación nos demuestra un mayor uso de terapia de reemplazo hormonal en la población femenina con grado de instrucción secundaria (n=40), en las pacientes sin antecedente patológicos (n=51), en las que no presentan antecedentes quirúrgicos (n=30) y en pacientes con sintomatología climatérica (n=46). Conclusiones: Se concluye en el estudio que hay una asociación estadísticamente significativa del uso de terapia de reemplazo hormonal con el grado de instrucción (p=0.009) (OR=4.6), con antecedentes patológicos (p=0.009) (OR=3.0), con antecedentes quirúrgicos (p=0.017) (OR=0.4) y con síntomas climatéricos (p=0.034) (OR=0.5). / -- The present investigation work has been carried out keeping in mind the Regulation of Grades and Holding of the School of Pre Grade of the Ability of Medicine of the National University bigger than San Marcos, with the purpose of obtaining Medical Surgeon's title. Objective: The investigation was guided to identify the factors of risk associated to the use of therapy of hormonal substitution, in women posmenopáusicas that were assisted in the Hospital National Archbishop Loayza in the period understood between January 01 and December of the 2009. Sample: The selected sample was understood by 178 patients, 89 cases and 89 controls. Instruments: Were the used instruments conformed by a record of gathering of data meetly elaborated for the study ends, was the association of the variables analyzed through the test of the square Chi, was the association force with OR, considered also?: 0,05. Type of Study: Observational. Investigation design: Analytic of cases and controls, traverse and retrospective. Result: The investigation demonstrates us a bigger use of therapy of hormonal substitution in the feminine population with grade of secondary instruction (n=40), in the patients without pathological antecedent (n=51), in those that don't present surgical antecedents (n=30) and in patient with sintomatología climacteric (n=46). Conclusions: You concludes in the study that there is an association statistically significant of the use of therapy of hormonal substitution with the instruction grade (p=0.009) (OR=4.6), with pathological antecedents (p=0.009) (OR=3.0), with surgical antecedents (p=0.017) (OR=0.4) and with symptoms climacteric’s (p=0.034) (OR=0.5). / Tesis

Oxy-Pherol-ET (OP-ET) is an artificial blood substitute composed of perfluoro~ributylamine (FC-43) emulsified with pluronic (FC-68) and hydroxyethyl starch as a plasma expander. This blood substitute is quite unique in that it has a high oxygen and carbon dioxide carrying capacity and is inert. In order for OP-ET to work, it must co-exist in circulation with blood components. This research project has been an investigation of the effect of OP-ET on the circulation regulatory agents (hormonal, etc). The aorta and vena cava were examined to assess the influence of OPET on the structural components of circulation. Since the kidney plays an important role in the overall regulation of circulation, the influence of the OP-ET on its function and structure were examined also. Stimulation of the renin-angiotensin system by hemorrhage, low sodium diet (LSD), and reduced renal perfusion pressure resulted in an increased release of renin in animals treated with OP-ET. Animals previously exchange-transfused with OP-ET were subsequently monitored daily for changes in weight, water intake, and urinary salt and water output. In OP-ET treated animals weight increase was when slow compared to control animals. The water intake of the animals exchange-transfused animals was substantially greater than control animals for the same time period. Animals prepared with indwelling catheters and exchange-transfused with OP-ET were monitored for their ability to respond to pharmacological concentrations of catecholamines and angiotensin II. Under these conditions animals showed no significant difference in blood pressure response when compared to control animals that were exchange-transfused with donor animals' RBCs and treated similarly with angiotensin and catecholamines. Previously transfused animals were monitored to determine the effect of OP-ET on the kidney. Under these conditions there was a diuretic-induced immediate increase in urinary sodium excretion and a gradual increase in urinary potassium. These were expected responses for this diuretic agent. Scanning electron microscopy (SEM) of exchange-transfused animals did not reveal observable differences within the endothelium of the aorta. The vena caval endothelium of the exchange-transfused animals showed no significant changes. There were no observable alterations in the glomerular capillaries by 7 days post-transfusion. The data warrant the conclusion that mechanisms which normally regulate the circulation still function in the presence of the blood substitutes used in this study. The use of OP-ET has great potential in emergency medicine and remote areas of the world where whole blood would be difficult to maintain.

No description available.

Women who use hormonal contraceptives have been shown to report more intense affective responses to partner infidelity than women with a natural cycle. Also, previous research suggests that female jealousy is sensitive to hormonal changes when naturally cycling, with a peak around ovulation, while women using hormonal contraceptives are less sensitive. This research is aimed at exploring women`s perception of couple conflicts in line with predictions derived from evolutionary theory. A factor analysis yielded four dimensions within 19 couple conflicts that were related to jealousy, emotional support, time and effort, and commitment. We tested the hypotheses that women who use hormonal contraceptives will react more strongly to jealousy-provoking scenarios and overall conflicts compared to women with a natural menstrual cycle. We also tested the hypotheses that naturally cycling women would show an increase in their emotional response to jealousy-provoking scenarios at days with high fertility risk. We expected that their emotional response to the scenarios infidelity, lack of emotional support, time and effort and lack of commitment, would increase if they perceived their partners as attractive. By using an online questionnaire, we followed women who were currently in a relationship with age ranging from 18 to 30 years weekly for 12 weeks. Results show a significant difference between women using hormonal contraceptives and naturally cycling women. Women using hormonal contraceptives responded to be more upset by scenarios indicating infidelity, than did naturally cycling women (p < .05), but not on the overall conflicts. However, some unexpected differences on the single scenarios where discovered. For the analysis concerning the fertility-effect, no significant main effect was found. However, our hypotheses were not supported (p > .001), Our results did, however, reveal a non-significant trending in the predicted direction indicating that the partner`s attractiveness interact with fertility status and affect how women respond to situations regarding Jealousy and couple conflicts.

Migrän är en återkommande form av huvudvärk som förmodas bero på hormonella, genetiska och miljörelaterade faktorer. Migrän finns i olika former men detta arbete fokuserar främst på migrän med aura och migrän utan aura. Det utmärkande för migrän med aura är neurologiska störningar som oftast uppstår innan attacken och kan yttra sig i form av tillexempel synstörningar. Det är en komplex sjukdom och uppkomsten är inte helt klarlagd. Smärtan som uppstår i samband med en migränattack förmodas bero på aktivering av det trigeminovaskulära systemet. Migrän anses som den 8:e mest betungande sjukdomen i världen och livskvalitén påverkas ofta negativt hos de individer som lider av migrän. Under en migränattack är det många individer som inte klarar av skol- eller jobbdagen, blir ofta sängliggande och sociala aktiviteter påverkas negativt. Behandlingsformer av migrän delas ofta upp i förebyggande eller anfallskuperande metoder och syftet med behandlingen är att hindra migränattackerna eller häva en pågående attack. Det förekommer både standardbehandling i form av tillexempel NSAID och triptaner. Dessutom finns det hormonell behandling som profylax i mensrelaterad migrän i form av olika hormoner. En stark riskfaktor för att drabbas av migrän är att ha släktingar som är lidande och ärftligheten kan vara så hög som 50%. Kvinnor drabbas oftare än män och bakgrunden till detta kan vara hormonella förändringar i kvinnokroppen, ofta sjunkande halter av östrogen. Denna litteraturstudie granskar sex artiklar, fyra om genetiska variationer vid migrän och två som berör hormonell behandling och migrän. Granskade artiklar visar att det finns en genetisk koppling till migrän, men det behövs fler studier för att få klarare och tydligare resultat. Några gener är länkade till både migrän med och utan aura, medan några är starkare i den ena formen av migrän. Resultat huruvida hormonell behandling kan ha en positiv effekt vid migrän är något klarare. / Migraines are a recurrent form of headache believed to be caused by hormonal, genetic and environmental factors. Migraines exist in different forms, but in this work, focuse is mainly on migraines with aura and migraines without aura. The characteristics of migraines with aura are neurological disorders that usually occur before the attack and can be expressed in the form of visual disturbances. It is a complex disease and the cause is not entirely clear. The pain that occurs in connection to a migraine attack is believed to be due to activation of the trigeminovascular system. Migraines are considered the 8th most burdensome disease in the world and the quality of life is often negatively affected in individuals suffering from migraines. During a migraine attack, many individuals fail to attend to school or to work, get often bedridden and social activities are adversely affected. Means of treatment of migraines are often divided into preventive or emergency methods and the purpose of both methods is to prevent migraine attacks. There are both standard treatments in the form of for example triptans and NSAIDs and there are hormonal treatments in the form of different hormones, such as estrogens. A strong risk factor for migraines is to have relatives who are suffering, the heredity may be as high as 50%. Women suffer more often than men and the background to this can be hormonal changes in the female body, often decreasing levels of estrogen. This literature review examines six articles, four on the link between genetics and migraine and two on hormonal treatment and migraine. Examined articles show that there is a genetic link to migraines, but more research is needed to get clearer results. Some genes are linked to both migraines with and without aura, while some are stronger in one form of migraine. There are some clearer indications that hormonal treatment may have a positive effect on migraines.

El climaterio es considerado una etapa importante en la vida de las mujeres, donde suceden diversos de cambios fisiológicos, actualmente existe el interés por evaluar los diversos síntomas empleando diversos instrumentos en todo el mundo. Por ello se realizó un estudio cuantitativo de nivel aplicativo, descriptivo, analítico y prospectivo de corte transversal a 396 pacientes cuyas edades era ≥40 años, cuyo objetivo fue analizar las principales modificaciones que afectan la calidad de vida en la mujer durante el climaterio; realizado en consultorios del Servicio de Ginecología y Obstetricia de la Clínica Centenario Peruano Japonesa. Se incluyeron a todas las pacientes ≥40 años, y excluyeron a pacientes con embarazo confirmado, analfabeta, trastornos serios de visión. Se utilizó el instrumento de Escala de Puntuación en Menopausia, compuesto de 11 preguntas agrupadas por el dominio somático, psicológico y urogenital; desarrollado por Heinemann y col. Se define como compromiso severo de la calidad de vida al puntaje total superior a 16 puntos, superior a 8 puntos para el domino somático, 6 puntos para el dominio psicológico y 3 puntos para el dominio urogenital. Los resultados muestran que 126 pacientes (31.8%) tiene un deterioro severo de su calidad de vida, siendo el domino urogenital el más afectado con una puntuación media de 3.3± 2.9, en un total de 154 pacientes (38.9%). La edad y la presencia de alguna enfermedad influyen en el deterioro de la calidad de vida. Se recomienda realizar estudios para evaluar beneficios de la terapia de reemplazo hormonal en mujeres durante el climaterio. Palabras claves: Calidad de vida, Climaterio, Escala de Puntuación en Menopausia. / --- The Climacteric is considered an important stage in the lives of women, where many physiological changes occur. There is currently interest in evaluating the various symptoms using several instruments around the world. Therefore, application-level quantitative, descriptive, analytical prospective crosssectional of 396 patients whose ages were more than 40 years, aimed at analyzing the main changes that affects the quality of life of women during menopause, performed in consultation offices of Gynaecology and Obstetrics in the Clínica Centenario Peruano Japonesa. We included all patients of ages more than 40 years old and excluded patients with confirmed pregnancy, illiteracy and serious eyesight disorders. The method used in this study was the Menopausal Rating Scale, consisting of 11 questions sorted by somatic, psychological and urogenital areas, developed by Heinemann et al. It is defined as a severe compromise of the quality of life to a score over 16 points, 8 points for the somatic area, 6 points for the psychological domain and 3 points for the urogenital domain. The results show that 126 patients (31.8%) have a sever impairment of their quality of life, being the urogenital domain the most affected with an average score of 3.3 +/- 2.9, from a total of 154 patients (38.9%). The age and the presence of any disease affect the deterioration of the quality of life. Studies are recommended to assess the benefits of hormone replacement therapy in women during climacteric. Key words: Quality of life, Climacteric, Menopause Rating Scale

Orientador: Sérgio Ricardo Batlouni / Resumo: Considerando as inconsistentes informações acerca dos protocolos de indução hormonal do Astyanax altiparanae em cativeiro, o principal objetivo deste estudo foi comparar o desempenho reprodutivo utilizando ou não extrato bruto de hipófise de carpa (EBHC). Avaliamos também o efeito de diferentes doses de EBHC sobre o desempenho reprodutivo em dois distintos lotes de peixes. Em todos os experimentos, avaliamos se um eventual ganho no desempenho reprodutivo estaria associado com alterações na morfologia dos ovários e/ou com concentrações séricas de prostaglandina F2α (PGF2α). Nos experimentos 1 (lote capturado na natureza) e 2 (lote nascido em cativeiro), aplicamos 3, 6 e 9 mg.kg-1 de EBHC (T1, T2 e T3 respectivamente), e um grupo controle (C). No experimento 3 (mesmo lote do experimento 2), comparamos o desempenho reprodutivo com dose única e fracionada (10% e 90% da dose total, com intervalo de 12 horas entre as doses) de EBHC, sendo 6 mg.kg-1 em dose única (H1) ou fracionada (H2) e seus respectivos controles (C1 e C2). Nos experimentos 1 e 2 o desempenho reprodutivo foi similar entre os grupos, porém os grupos T2 e T3 apresentaram elevações de PGF2α no momento da ovulação, além de variações significativas nas frequências de estruturas ovarianas, que indicam aumento da ovulação e /ou a maturação final. No experimento 3, a dose fracionada de 6 mg.kg-1 de EBHC causou um aumento na proporção de réplicas com desova e consequentemente, no volume total de desova e no número total de... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Considering the inconsistent information about the hormonal induction protocols of Astyanax altiparanae in captivity, the main objective of this study was to compare the reproductive performance with or without crude carp pituitary extract (EBHC). We also evaluated the effect of different doses of EBHC on the reproductive performance of two distinct broodstocks. In all experiments, we evaluated whether a possible gain in reproductive performance would be associated with changes in ovarian morphology and / or with serum prostaglandin F2α (PGF2α) concentrations. In the experiments 1 (wild caught) and 2 (born in captivity), we applied 3, 6 and 9 mg.kg-1 EBHC (T1, T2 and T3 respectively), and one control group (C). In the experiment 3 (same broodstock as in experiment 2), we compared reproductive performance with single and fractional doses (10% e 90% of the total, with 12 hours of interval between doses) of EBHC, being: 6 mg.kg-1 in single dose (H1) or fractional (H2) and their respective controls (C1 and C2). In the experiments 1 and 2 the reproductive performance was similar between groups, but groups T2 and T3 presented elevations of PGF2α at the time of ovulation, besides significant variations in the frequencies of ovarian structures, which indicates increase in ovulation and / or final maturation. In the experiment 3, the fractional dose of 6 mg.kg-1 EBHC caused an increase in the proportion of replicates with spawn events and consequently, in the total volume of eggs and ... (Complete abstract click electronic access below) / Doutor

Orientador: Eduardo Antônio Sanches / Resumo: O Brasil apresenta um grande potencial para produção de peixes em ambientes marinhos/estuarinos, entretanto, isso ainda não é realidade por vários fatores, dentre eles a tecnologia de produção ainda limitada de algumas espécies nativas promissoras, como é o caso do robalo-flecha Centropomus undecimalis. Assim, o objetivo deste estudo foi avaliar o desempenho zootécnico e desenvolvimento gonadal de juvenis de C. undecimalis após alimentação com ração (45% PB) contendo 17β-estradiol (E2) e 17α-metiltestosterona (MT). Para tanto, 450 peixes (um ano de idade) foram submetidos a um delineamento experimental inteiramente casualizado contendo três tratamentos em triplicata. Os tratamentos foram: 1ª) ração sem adição de hormônio (grupo controle); 2ª) ração com 100 mg de E2 por kg; 3ª) ração com 60 mg de MT por kg,, fornecidas durante 55 dias. Após o término da alimentação com hormônio os peixes foram alimentados com a mesma ração, sem adição de hormônio, durante 313 dias, totalizando 368 dias. Não se verificou efeito (P>0,05) dos tratamentos sobre os parâmetros zootécnicos avaliados. Não foram encontradas estruturas morfológicas da completa diferenciação sexual ou não se observou células especificas de ovários ou testículos ao final dos 368 dias. Conclui-se que as alimentações contendo 17βestradiol e 17α-metiltestosterona não influenciaram o desempenho zootécnico de juvenis de C. undecimalis após um ano de alimentação. / Abstract: The Brazil has great potential for fish production in marine/estuarine environments, however, this is not yet reality due to several factors, including the still limited production technology of some promising native species, such as the common snook, Centropomus undecimalis. Thus, the objective of this study was to evaluate the zootechnical performance and gonadal development of juveniles of C. undecimalis after feeding with feed (45% CP) containing 17β-estradiol (E2) and 17α-methyltestosterone (MT). To that end, 450 fish (one year old) were submitted to a completely randomized experimental design containing three treatments in triplicate. The treatments were: 1st) ration without addition of hormone (control group); 2nd) ration with 100 mg of E2 per kg; 3rd) ration with 60 mg MT per kg, provided for 55 days. After the end of the feeding with hormone the fish were fed the same feed, without addition of hormone, during 313 days, totaling 368 days. There was no effect (P>0.05) of the treatments on the zootechnical parameters evaluated. No morphological structures were found of complete sexual differentiation or no specific ovary or testis cells were observed at the end of 368 days. It was concluded that feeds containing 17β-estradiol and 17αmethyltestosterone did not influence the performance of juveniles of C. undecimalis after one year of feeding. KEY-WORDS: feminization, masculinization, hormonal administration, marine fish farming. / Mestre

Migraine is a frequent debilitating neurological disorder that is considered to be genetically complex with a multifactorial mode of inheritance. It has a high prevalence with approximately 18% of women and 6% of men suffering from the disorder. Migraine is characterized by severe head pain with associated nausea, emesis, photophobia, phonophobia, and neurological disturbances. The International Headache Society (IHS) has classified various types of migraine according to their clinical features. The two main subtypes of migraine are migraine without aura (MO), occurring in ~70-75% of migraineurs, and migraine with aura (MA) which occurs in ~25% of migraineurs. Some people experience both types of attack in their lives. While the precise pathogenesis of migraine is unknown, it is widely accepted that short-term alterations in neuronal activity occur in relation to the attack, along with temporary changes in the cerebral vasculature. Trigeminal nerve activation is also considered pivotal to progression of a migraine attack. Neurotransmitters, especially serotonin (5-hydroxytryptamine, 5-HT), platelet activation and sympathetic hyperactivity all appear to play a part, whether as part of the primary triggering event, or as a response mechanism. Migraine imparts a significant burden on society, both socially and financially. The World Health Organization has identified migraine among the world's top 20 leading causes of disability, with an impact that extends far beyond individual suffering. There is significant evidence from family and twin studies to indicate a strong genetic component to migraine. The current understanding of migraine is that it is a polygenic multifactorial disorder. It has been postulated that genetic factors set the individual migraine threshold, with environmental influences playing a modulating role. It is likely that many genes may provide an important although moderate contribution to an individual’s migraine susceptibility. The identification of migraine susceptibility genes has been the focus of substantial research to date and could eventually lead to improved treatments and greater understanding of the disorder. Several loci have shown promise, although these need to be followed up by both replication and functional studies to determine a definitive causative role. This research investigated the role of both hormonal and vascular related genes as candidate genes that may play a role in migraine susceptibility due to the well-known role of hormones and vascular changes in some migraineurs. The estrogen receptor (ESR) and progesterone receptor (PGR) genes are potential migraine candidates due to the recognized hormonal influence on migraine susceptibility. Migraines in women frequently occur during the childbearing years and are often influenced by significant hormonal milestones. The fluctuating hormone levels of the menstrual cycle have been implicated in migraine but a definitive role is yet to be established. It has been suggested that factors additional to circulating hormone levels may be at play. This research considered that variation in the ESR 1 and PGR genes may confer an increased migraine risk. To investigate the potential role of these genes in migraine, association studies investigating variants in ESR 1 and PGR were undertaken in two independent casecontrol cohorts. This was followed up by mutation screening and gene expression analysis in an effort to elucidate a functional role for these genes in the pathogenesis of migraine. Vascular genes also represent likely migraine candidates as alterations in both vascular function and cerebral blood flow are well known in migraine. Furthermore, cortical spreading depression (CSD), a depolarization wave that propagates across the brain cortex and has been speculated to cause the neurological symptoms that present in MA, has also been linked to vascular dysfunction. The methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTRR) genes both play a role in vascular functioning and were thus considered potential migraine candidates for this study. Both are involved in the pathway of homocysteine metabolism. Impaired activity of these enzymes can lead to mild hyperhomocysteinemia which is believed to lead to oxidative arterial damage. This may in turn impact on migraine susceptibility, possibly through the activation of trigeminal fibres. The MTHFR 677T allele results in an amino acid change in the catalytic domain of the enzyme leading to mild hyperhomocysteinemia. This particular variant has been implicated in migraine in four separate studies. One of these studies also suggested a role for the MTHFR 1298C allele in migraine. This allele also results in an amino acid change and reduced enzyme activity. Similarly, the MTRR 66G allele results in an amino acid change and has been associated with reduced activity of MTRR and increased plasma homocysteine concentration. To investigate the role of the ESR 1, PGR, MTHFR and MTRR genes in migraine, samples from two large independent case control cohorts were investigated. Cohort 1 was comprised of 275 migraineur samples and 275 age, sex and ethnicity matched controls while cohort 2 comprised 300 cases and 300 matched controls. All individuals were collected at the Genomics Research Centre with migraine diagnosis undertaken by HIS criteria and migraine affected individuals designated as MO or MA. Results of analysis of ESR 1 indicated a positive association with migraine in the two large independent cohorts for the exon 8 G594A polymorphism (P = 0.003; P = 8x10-6). Similarly, the PGR analysis showed a positive association with migraine for the PROGINS allele (P = 0.02; P = 0.003). Results also showed that individuals with both ESR 1 and PGR susceptibility alleles were 3.2 times more likely to suffer migraine those those with no susceptibility alleles. As the ESR 1 variant is synonymous, a mutation analysis was undertaken in a small sub-sample of individuals carrying the susceptibility allele, but no mutations were detected in these particular samples. Detailed mutation analysis of ESR 1 in a larger study group may be warranted. An ESR 1 and PGR expression analysis by RT-PCR was undertaken to examine if there were any notable expression level changes in migraineurs versus controls and additionally whether the susceptibility genotypes influenced gene expression. Altered expression levels may point to a functional change in the gene. Although results did not show any significant difference in expression levels in the case/control group, nor any influence in gene expression conferred by the specific susceptibility genotypes, ESR 1 expression did appear to be down-regulated in the migraine group and more specifically in the migraine susceptibility genotype subgroup. A larger study group may therefore be warranted to detect any potential genuine changes in gene expression. Overall, these results suggested that these hormonal genes appear to play a role in migraine susceptibility, although further studies are needed to define this. Results of the MTHFR 677 analysis showed that the TT genotype was significantly associated with the MA subgroup in a joint analysis of the two independent cohorts (P = 0.004). Results of analysis of MTHFR 1298, which is tightly linked to the 677 locus, showed a significant association in female migraineurs (P = 0.009). Similarly, results of the MTRR analysis also showed a significant difference between the female case and control groups with the G allele over-represented in female migraineurs (P = 0.022) These results may indicate that a significant gender effect appears in this locus as well as the MTHFR 1298 locus although results may also be due to a larger number of female migraineurs conferring increased statistical power to the gender subgroup. Interaction analysis of the MTHFR 1298 locus and the MTRR locus showed that females who carried both variants under a recessive model were 5 times more likely to suffer migraine those those with no susceptibility genotypes. Overall these results indicated that these vascular genes appear to play a role in migraine susceptibility. The final study focused on 6 genetic variants that had shown a positive association with migraine and/or MA in the same large association population analysed in this research. The aim of this study was to provide preliminary data on the potential role of genetic profiling in migraine. Using the genotypic data to create vascular and hormonal risk profiles based on positive association and interaction of MTHFR 677 T and ACE D alleles, and MTHFR 1298 AA and MTRR GG genotypes as vascular variants; and positive association and interaction of ESR 1 594 A and PGR PROGINS as hormonal variants, this study was able to demonstrate the relevance of genetic risk profiling to migraine. Results showed a significantly higher proportion of individuals with at least one genetic risk profile in the migraine group compared to those in the control group (P = 6 x 10-6). Individuals who possessed either the vascular and/or hormonal genetic risk profile were 8.6 times more likely to suffer from migraine than those who possessed a ‘no risk’ profile. This indicated a greater effect than the individual effect of each of these variants. Furthermore individuals who possessed a vascular or both risk profiles were more likely to suffer nausea, emesis, phonophobia and photophobia, and have a mother who also suffered migraine. Overall, the genetic profiling approach provided interesting preliminary data on migraine susceptibility and indicated that such an approach may prove very useful for migraine diagnosis, particularly when all migraine genes have been identified. In conclusion this study provided the first indication that hormone receptor genes play a role in migraine susceptibility. Hormones have long been considered to play a role in the disorder but this study has provided the first molecular evidence to support this premise. In addition, this study showed that vascular related genes also play a role in migraine susceptibility. Finally, this study has clearly shown that migraine is a complex disorder involving multiple genes. Although a number of studies have implicated neurotransmitter related genes in the disorder, the present study is the first to show that both vascular and hormonal genes also play a role in migraine susceptibility. Thus there now appear to be three classes of genes that affect migraine susceptibility and although this study has implicated new variants, the preliminary genetic profiling study has shown that not all predisposing variants involved in the disorder have been defined.

Durant la grossesse, 30 g de calcium de la mère vers le foetus sont transférés à travers le placenta à raison de 140 mg/Kg/jour pendant le troisième trimestre. Cet apport calcique est primordial au bon développement du foetus notamment dans la formation de ses os et ses dents. De plus, le calcium passant au travers du placenta provient à la fois de la diète maternelle et de la résorption des os maternels afin de subvenir convenablement aux besoins foetaux. Il est donc essentiel que la consommation de calcium par la mère soit suffisante, qu'il y ait une bonne efficacité du transport transplacentaire et que le foetus présente une bonne aptitude à fixer cet ion. Il existe des protéines permettant le transport de calcium comme les canaux TRPV faisant passer le calcium de la circulation maternelle vers le cytoplasme des syncytiotrophoblastes, les CaBPs responsables du transport de calcium dans le cytoplasme, ainsi que la pompe PMCA assurant le transfert du calcium des syncytiotrophoblastes vers la circulation foetale contre le gradient de calcium, aidées potentiellement par l'échangeur Na+/Ca2+. Le but de cette étude est de caractériser la régulation de l'expression de ces protéines responsables du transfert calcique dans le placenta en fonction de la présence ou non de l'action des hormones PTH et PTHrP via le récepteur PTH1R. En effet, ces deux hormones favoriseraient l'expression des protéines à caractère calcium en se liant au récepteur PTH1R. La lignée de cellules de carcinome humain (JEG-3) est traitée ou non avec l'antagoniste aux deux récepteurs PTH (7-34). Les cellules sont traitées pendant 4 jours, et les ARNm sont extraits après 2 et 4 jours de traitement. L'expression des différentes protéines à calcium est quantifiée par PCR en temps réel. On s'attendrait à une diminution de l'expression de celles-ci en absence de signalisation via le récepteur PTH1R puisque PTHrP est un facteur connu pour maintenir le gradient calcique allant de la circulation maternelle à foetale, et que sa concentration dans la circulation augmente fortement au moment où le transport de calcium est à son maximum; et la PTH est également connu pour être un facteur hypercalcémiant. ______________________________________________________________________________ MOTS-CLÉS DE L’AUTEUR : Placenta, Calcium, Transport, PTH, PTHrP, PTH1R.