Influxos do céu na existência dos homens. Os escritos astrológicos na Península Ibérica (séculos XIII, XIV e XV)

Pós-graduação em História - FCHS

Aspectos do amor no Roman de la Rose de Guillaume de Lorris e Jean de Meun (Século XIII)

Pós-graduação em História - FCLAS

Studies on the Helminth Fauna of Alaska. XIII. Disease in the Sea Otter, with Special Reference to Helminth Parasites

During the spring of 1951, the U. S. Fish and Wildlife Service undertook the removal of sea otter, Enhydra lutris (L)., from the Aleutian Island of Amchitka, for the purpose of restocking range from which the animals have long been exterminated. The decision to undertake this activity was influenced by the nature of military operations planned for the island later the same year. The capture and removal of the otter were under the supervision of Mr. Robert D. Jones, Biologist, U. S. Fish and Wildlife Service. Heavy losses among the animals shortly after capture made the venture unsuccessful. Many deaths were concurrent among animals in the wild state. The writer was asked to investigate the causes of disease in the sea otter, and it is the purpose of this paper to report the results of these investigation, with special reference to helminth parasites.

Purification of coagulation factor VIII using chromatographic methods. Direct chromatography of plasma in anion exchange resins

Coagulation factor VIII (FVIII) concentrates are used in the treatment of patients with Hemophilia A. Human FVIII was purified directly from plasma using anion exchange chromatography followed by gel filtration. Three Q-Sepharose resins were tested, resulting in 40% recovery of FVIII activity using Q-Sepharose XL resin, about 80% using Q-Sepharose Fast Flow and 70% using the Q-Sepharose Big Beads. The vitamin K-dependent coagulation factors co-eluted with FVIII from the anion exchange columns. In the second step of purification, when Sepharose 6FF was used, 70% of FVIII activity was recovered free from vitamin K-dependent factors.

Production of human factor VIII-FL in 293T cells using the bicistronic MGMT(P140K)-retroviral vector

Hemophilia A is the most common X-linked bleeding disorder; it is caused by deficiency of coagulation factor VIII (FVIII). Replacement therapy with rFVIII produced from human cell line is a major goal for treating hemophilia patients. We prepared a full-length recombinant FVIII (FVIII-FL), using the pMFG-P140K retroviral vector. The IRES DNA fragment was cloned upstream to the P140K gene, providing a 9.34-kb bicistronic vector. FVIII-FL cDNA was then cloned upstream to IRES, resulting in a 16.6-kb construct. In parallel, an eGFP control vector was generated, resulting in a 10.1-kb construct. The 293T cells were transfected with these constructs, generating the 293T-FVIII-FL/P140K and 293T-eGFP/P140K cell lines. In 293T-FVIII-FL/P140K cells, FVIII and P140K mRNAs levels were 4,410 (+/- 931.7)- and 295,400 (+/- 75,769)-fold higher than in virgin cells. In 293T-eGFP/P140K cells, the eGFP and P140K mRNAs levels were 1,501,000 (+/- 493,700)- and 308,000 (+/- 139,300)-fold higher than in virgin cells. The amount of FVIII-FL was 0.2 IU/mL and 45 ng/mL FVIII cells or 4.4 IU/mu g protein. These data demonstrate the efficacy of the bicistronic retroviral vector expressing FVIII-FL and MGMT(P140K), showing that it could be used for producing the FVIII-FL protein in a human cell line.

SK-HEP cells and lentiviral vector for production of human recombinant factor VIII

Hemophilia A is caused by a deficiency in coagulation factor VIII. Recombinant factor VIII can be used as an alternative although it is unavailable for most patients. Here, we describe the production of a human recombinant B-domain-deleted FVIII (rBDDFVIII) by the human cell line SK-HEP-1, modified by a lentiviral vector rBDDFVIII was produced by recombinant SK-HEP cells (rSK-HEP) at 1.5-2.1 IU/10(6) in 24 h. The recombinant factor had increased in vitro stability when compared to commercial pdFVIII. The functionality of rBDDFVIII was shown by its biological activity and by tail-clip challenge in hemophilia A mice. The rSK-HEP cells grew in a scalable system and produced active rBDDFVIII, indicating that this platform production can be optimized to meet the commercial production scale needs.

Combined oral contraceptives and increasing cardiovascular risk: thromboembolism and hypertension

Background: Hormonal contraceptive pills are the most used reversible method for familiar planning in Brazil. The combined pill, with synthetic analogs of estrogen and progestin, is employed by 25% of Brazilian female population. Its use provokes an increase of blood pressure levels, takes patient to a hipercoagulability state and predisposes her to thromboembolic events. Purposes: We aimed to describe mechanisms of hypercoagulability promoted by oral combined contraceptives, to analyze the relative risk of cardiovascular events within users and to list the most common circulatory pathologies in these patients. Methods: Three virtual medical databases were surveyed (Pubmed/Medline, BVS/LILACS and Scielo). Twelve studies were selected: clinical trials, case reports and articles of indexed medical periodic originally published in Portuguese and English about synthetic hormones, oral contraception, coagulation disorders and cardiovascular morbimortality. Results: Synthetic estrogen promotes an increase of some clotting factors' levels (VII, VIII, IX, X, XII, XIII and fibrinogen), such as a reduction of their inhibitors (S protein and antithrombin). Because of this, etinilestradiol is the component most related to venous thrombosis and ischemic diseases of brain and heart. It also improves the releasing of hepatic angiotensinogen, taking to a increase of blood pressure levels. Conclusions: The prescription of oral combined contraceptives needs criteria, notably due to adverse effects of etinilestradiol. It is recommended to avoid the administration of these drugs for patients elder than 35 year-old or with risk factors. For these patients, the use of progestagen-only pills seems to be safer.

Mechanisms of ring chromosome formation, ring instability and clinical consequences

Background The breakpoints and mechanisms of ring chromosome formation were studied and mapped in 14 patients. Methods Several techniques were performed such as genome-wide array, MLPA (Multiplex Ligation-Dependent Probe Amplification) and FISH (Fluorescent in situ Hybridization). Results The ring chromosomes of patients I to XIV were determined to be, respectively: r(3)(p26.1q29), r(4)(p16.3q35.2), r(10)(p15.3q26.2), r(10)(p15.3q26.13), r(13)(p13q31.1), r(13)(p13q34), r(14)(p13q32.33), r(15)(p13q26.2), r(18)(p11.32q22.2), r(18)(p11.32q21.33), r(18)(p11.21q23), r(22)(p13q13.33), r(22)(p13q13.2), and r(22)(p13q13.2). These rings were found to have been formed by different mechanisms, such as: breaks in both chromosome arms followed by end-to-end reunion (patients IV, VIII, IX, XI, XIII and XIV); a break in one chromosome arm followed by fusion with the subtelomeric region of the other (patients I and II); a break in one chromosome arm followed by fusion with the opposite telomeric region (patients III and X); fusion of two subtelomeric regions (patient VII); and telomere-telomere fusion (patient XII). Thus, the r(14) and one r(22) can be considered complete rings, since there was no loss of relevant genetic material. Two patients (V and VI) with r(13) showed duplication along with terminal deletion of 13q, one of them proved to be inverted, a mechanism known as inv-dup-del. Ring instability was detected by ring loss and secondary aberrations in all but three patients, who presented stable ring chromosomes (II, XIII and XIV). Conclusions We concluded that the clinical phenotype of patients with ring chromosomes may be related with different factors, including gene haploinsufficiency, gene duplications and ring instability. Epigenetic factors due to the circular architecture of ring chromosomes must also be considered, since even complete ring chromosomes can result in phenotypic alterations, as observed in our patients with complete r(14) and r(22).

Espacios de nadie y de todos: Territorio y sociedad en la frontera andalusí al norte del Tajo extremeño (Siglos VIII-XI)

[ES]Entre mediados del siglo VIII y mediados del siglo XII, el espacio comprendido entre el Sistema Central y el río Tajo en su parte extremeña ejerció como confín territorial de al- Andalus. A lo largo de todo este tiempo se sucedieron distintas fases en las que la frontera fluctuó según vinieran los aires cristianos del norte o islámicos del sur. Ello provocaría que estos territorios actuaran con relativa autonomía en muchos momentos de su historia andalusí y que se convirtieran en zonas donde confluían gentes de toda condición social y religiosa. En el presente trabajo tratamos de vislumbrar las dinámicas territoriales y sociales que se dieron en aquella región hasta finales del siglo XI, cuando se produjeron las conquistas cristianas de las ciudades islámicas más importantes de la frontera. [EN] The geographical area between the Spanish Central System and the part of the Tagus passing through Extremadura served as the boundary of the al-Andalus from the 8th to the 12th century. The boundary had different phases that fluctuated according to the influence exercised by the northern Christians or southern Muslims. This allowed these territories to have relative autonomy during its Andalusian history and turned them into zones where people from different social and religious background converged. The aim of this paper is to analyse the territorial and social dynamics of this area until the end of the 11th century, when the Christians conquered the most important Islamic towns of the borderland.

Synthetic and mechanistic investigation of new radical processes: reaction of organic azides with group-XIII Lewis acids

Dichloroindium hydride revealed to be a valid alternative to tributyltin hydride for radical reduction of organic (alkyl, aryl, acyl, solfonyl) azides. The new approach entails mild reaction conditions and provides high yields of the corresponding amines and amides, also showing high degrees of selectivity. The system dichloroindium hydride / azides can be utilised in fivemembered ring closures of g-azidonitriles, as a new source of aminyl radicals for the attractive synthesis of interesting amidine compounds in the absence of both toxic reagents and tedious purification procedures. Allylindium dichloride seems a good substitute for dichloroindium hydride for generation of indium centred radicals under photolytic conditions, since it allows allylation of electrophilic azides (e.g. phenylsulfonyl azide) and halogen or ester δ-substituted azides, the latter through a 1,5-H transfer rearrangement mechanism. Evidences of the radical nature of the reactions mechanism were provided by ESR spectroscopy, furthermore the same technique, allowed to discover that the reaction of azides with indium trichloride and other group XIII Lewis acids, in particular gallium trichloride, gives rise to strongly coloured, persistent paramagnetic species, whose structure is consistent with the radical cation of the head-to-tail dimer of the aniline corresponding to the starting azide.