Development of an Interleukin-1β Vaccine in Patients with Type 2 Diabetes

Interleukin-1β (IL-1β) is a key cytokine involved in inflammatory illnesses including rare hereditary diseases and common chronic inflammatory conditions as gout, rheumatoid arthritis, and type 2 diabetes mellitus, suggesting reduction of IL-1β activity as new treatment strategy. The objective of our study was to assess safety, antibody response, and preliminary efficacy of a novel vaccine against IL-1β. The vaccine hIL1bQb consisting of full-length, recombinant IL-1β coupled to virus-like particles was tested in a preclinical and clinical, randomized, placebo-controlled, double-blind study in patients with type 2 diabetes. The preclinical simian study showed prompt induction of IL-1β-specific antibodies upon vaccination, while neutralizing antibodies appeared with delay. In the clinical study with 48 type 2 diabetic patients, neutralizing IL-1β-specific antibody responses were detectable after six injections with doses of 900 µg. The development of neutralizing antibodies was associated with higher number of study drug injections, lower baseline body mass index, improvement of glycemia, and C-reactive protein (CRP). The vaccine hIL1bQb was safe and well-tolerated with no differences regarding adverse events between patients receiving hIL1bQb compared to placebo. This is the first description of a vaccine against IL-1β and represents a new treatment option for IL-1β-dependent diseases such as type 2 diabetes mellitus (ClinicalTrials.gov NCT00924105).Molecular Therapy (2016); doi:10.1038/mt.2015.227.

Jean-Martin Charcot - Neurologist by Avocation, Nephrologist by Yearning

In an age of medical advances and specialization, Jean-Martin Charcot (1825-1893) helped found the discipline of neurology and in 1882 was appointed the first professor of Diseases of the Nervous System in France. As an investigator with broad interests and vast knowledge Charcot contributed to several other disciplines. An early mentor and dominant figure in Charcot's formative years was Pierre Rayer (1793-1867), famous for his seminal contributions to the study of the kidney, who gifted Charcot with his passion for clinical pathological correlations and likely a yearning for the study of kidney diseases. Famous for the clarity and incisiveness of his formal teaching presentations, Charcot lectured on the kidney at the Faculty of Medicine in Paris in 1877. Translated into English and published as a book titled Lectures on Bright's Disease, they became widely accessible and quoted in the literature through the present. In addition, at a time that he was already concentrating on the study of neurological disorders, Charcot maintained his life-long interest in the kidney and published original studies on the pathological changes of the kidney in gout and experimental lead poisoning, as well as supporting a study of hysterical ischuria by his students.

Transport, Compartmentation, and Metabolism of Homoserine in Higher Plant Cells : Carbon-13- and Phosphorus-31-Nuclear Magnetic Resonance Studies

The transport, compartmentation, and metabolism of homoserine was characterized in two strains of meristematic higher plant cells, the dicotyledonous sycamore (Acer pseudoplatanus) and the monocotyledonous weed Echinochloa colonum. Homoserine is an intermediate in the synthesis of the aspartate-derived amino acids methionine, threonine (Thr), and isoleucine. Using 13C-nuclear magnetic resonance, we showed that homoserine actively entered the cells via a high-affinity proton-symport carrier (Km approximately 50–60 μm) at the maximum rate of 8 ± 0.5 μmol h−1 g−1 cell wet weight, and in competition with serine or Thr. We could visualize the compartmentation of homoserine, and observed that it accumulated at a concentration 4 to 5 times higher in the cytoplasm than in the large vacuolar compartment. 31P-nuclear magnetic resonance permitted us to analyze the phosphorylation of homoserine. When sycamore cells were incubated with 100 μm homoserine, phosphohomoserine steadily accumulated in the cytoplasmic compartment over 24 h at the constant rate of 0.7 μmol h−1 g−1 cell wet weight, indicating that homoserine kinase was not inhibited in vivo by its product, phosphohomoserine. The rate of metabolism of phosphohomoserine was much lower (0.06 μmol h−1 g−1 cell wet weight) and essentially sustained Thr accumulation. Similarly, homoserine was actively incorporated by E. colonum cells. However, in contrast to what was seen in sycamore cells, large accumulations of Thr were observed, whereas the intracellular concentration of homoserine remained low, and phosphohomoserine did not accumulate. These differences with sycamore cells were attributed to the presence of a higher Thr synthase activity in this strain of monocot cells.

Artrites microcristalinas : experiência da consulta de osteoartrose e artrites microcristalinas do Serviço de Reumatologia do Centro Hospitalar Lisboa Norte, E.P.E.

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Oeuvres de Monsieur de Montesquieu.

Contiene: Les Considérations sur les causes de la grandeur des Romains [et] de leur décadence (P 1-284). Le Dialogue de Sylla [et] d'Eucrate (P. 285-300). Le temple de Gnide (P. 301-361). Essai sur le Goût, fragment (P. 362-407)

[Oeuvres de François Joachim de Pierre, cardinal de Bernis]

Contiene: Discours sur la poesie (p. 1-12), Epitres sur le gout et sur les moeurs (p. 13-42), Poesies diverses (p. 43-52), Reflexions sur les passions et sur les gouts (p. 53-144), Poesies diverses (145-181)

De gutta siue iuncturarum dolore quem arthritim dicunt /

Mode of access: Internet.

Oeuvres de Monsieur de Montesquieu.

Contiene : Considérations sur les cause de la grandeur des romains, et de leur décadence ; Dialogue de Sylla et D'Eucrate ; Le temple de Gnide ; Essai sur le gout, fragment.

Réponse à la dissertation sur la goutte /

Mode of access: Internet.

Oeuvres de Monsieur de Montesquieu : tome troisieme.

Mode of access: Internet.

Tratado práctico de la gota : en el qual se indican los medios de curar esta enfermedad /

Mode of access: Internet.

Demetrii Pepagomeni Liber de podagra graece et latine /

Mode of access: Internet.

The dramatic works of Edwin Atherstone ...

Pelopidas; or, The deliverance of Thebes.--Philip.--Love, poetry, philosophy and gout.

Traité de la goutte dans son etat naturel ou, L'art de connoistre les vrais principes des maladies : avec plusieurs remedes conformes au systême d'Hippocrate, de Galien, & de Vanhelmont ... /

Mode of access: Internet.

Catalogue des plantes du Limousin. Tome 1-2 ...

"Ouvrage édité par la Société botanique et d'études scientifiques du Limousin".