Oncobiguanides: Paracelsus" law and nonconventional routes for administering diabetobiguanides for cancer treatment

The dose makes the poison, the common motto of toxicology first expressed by Paracelsus more than 400 years ago, may effectively serve to guide potential applications for metformin and related biguanides in oncology. While Paracelsus' law for the dose-response effect has been commonly exploited for the use of some anti-cancer drugs at lower doses in non-neoplastic diseases (e.g., methotrexate), the opposite scenario also holds true; in other words, higher doses of non-oncology drugs, such as anti-diabetic biguanides, might exert direct anti-neoplastic effects. Here, we propose that, as for any drug, there is a dose range for biguanides that is without any effect, one corresponding to"diabetobiguanides" with a pharmacological effect (e.g., insulin sensitization in type 2 diabetes, prevention of insulin-dependent carcinogenesis, indirect inhibition of insulin and growth factor-dependent cancer growth) but with minimal toxicity and another corresponding to 'oncobiguanides' with pharmacological (i.e., direct and strong anticancer activity against cancer cells) as well as toxic effects. Considering that biguanides demonstrate a better safety profile than most oncology drugs in current use, we should contemplate the possibility of administering biguanides through non-conventional routes (e.g., inhaled for carcinomas of the lung, topical for skin cancers, intravenous as an adjunctive therapy, rectal suppositories for rectal cancer) to unambiguously investigate the therapeutic value of high-dose transient biguanide exposure in cancer. Perhaps then, the oncobiguanides, as we call them here, could be viewed as a mechanistically different type of anti-cancer drugs employed at doses notably higher than those used chronically when functioning as diabetobiguanides

Os três princípios e as doenças: a visão de dois filósofos químicos

Paracelsus (1493 - 1541) developed a theory about three principles (sulphur, mercury, and salt) that would constitute matter, and whose mutual interactions within man's body could cause diseases. This paper discusses the influence of this theory on the work of two chemical philosophers. Oswald Crollius (1560 - 1609) considered that the conceptions of matter and disease were strongly related because of the macro - microcosm analogy, and classified diseases in sulphurean, mercurial and saline. On the other hand, J. B. Van Helmont (1579 - 1644) stated that sulphur, mercury, and salt were not true principles, and that every disease would have a specific origin. Instead of the principles, Van Helmont put the Archeus at the center of both his medical and matter theories.

Recueil d'épitaphes, précédé d'un journal des principaux événements arrivés à Paris de 1557 à 1590.

Contient : 1 Journal autographe de JEHAN DE LA FOSSE, où sont notés mois par mois les principaux événements des années 1557 à 1590, arrivés en France et particulièrement à Paris, où vivait l'auteur, curé de St-Leu et de St-Barthélemy ; 2 Recueil d'épitaphes ; « Cavendish,... general Norris,... docter Story,... mylord Treasurer,... Frier Andrew,... Ellis,... earle of Essex, beheaded in the tower », Joannes Rekingale, episcopus Cicestriensis, Gulielmus de Blitz, archidiaconus Nodovicensis ; Thomas Linaerus, regis Henrici VIII medicus, Antonius Riccius Faventiae, « Mr Hofkins », Lucretia Borgia, Honorius P. M., Johannes Riberius ; Galfridus Chaucer, Corythus, filius Oenones et Paridis, Ninus, Assyriae monarcha, Pyramis, lateritia Asychis, Aegypti regis ; Bartholomaeus Platina, Petrus Pomponatius, Pompeius Magnus, Capys, Ennius, Hannibal ; Marcus Antonius Turrianus, Marcus Antonius Coccius, Marcus Antonius Casanova, Sardanapalus, Rufus, Julius Caesar, Augustus Caesar ; Petrus Ciaconius, Nicolaus Macchiavellus, Gulielmus Rondeletus, medicus, Anicia, foemina romana, Callicratea ; Johannes Coletus, Rembertus Dodonaeus, medicus Maximiliani II et Rodolphi imperatorum, Alcaeus poeta, Scipio Africanus ; Paracelsus, Gerardus Noviomagus et Andreas Hyperius, Didacus de Valdes, Albericus de Vere et Gulielmus, primus comes Oxoniensis, Robertus Buc ; Hieronymus Cagnolus Vercellensis, Johannes Stofflerus, mathematicus Tubingae, Remigius Bellaqueus, Pallas, Evandri filius, Zarmanochegas indus, de Bargosa ; Johannes Rivius Attbend, Petrus Bembus, Lucius P. M. Veronae, Gulielmus Norselez, decanus quondam ecclesiae S. Pauli Londini, Mathias Corvinus, rex Pannoniae ; Philippus Callimachus Cracoviae, in aede S. Trinitatis, Ludovicus Bologninus, Bononiae, Rachel, uxor Jacobi Bethleem, Aratus, Plato, Aeschylus ; Joannes Zonaras, Homerus, Menander, Epictetus ; Berengarius, archidiaconus Andegavensis, Andreas Fanzonius, Cyrus, Persarum monarcha, Midas ; Hugo S. Victoris Parisiensis, S. Bernardus, abbas claraevallensis, Petrus de Toledo, Psittacus, Musaeus poeta, Linus, thebanus poeta, Orpheus ; Petrus Lombardus, Petrus Comestor, Pallas, libertus Romae, Megista, Spartanus vates ; Aegidius de Roma, archiepiscopus Bituricensis, Johannes Gerson, Aristocrates, perfidus in Lycaei Jovis luco, Setho, sacerdos Vulcani et Aegypti rex, Rosamunda Cliffordensis, Petrus Aretinus ; Nicolaus de Lyra, Jacobus Pisaurus, Paphi episcopus, Cedwalla, rex Sussexiae ; Alphonsus Tostadus, hispanus, Abulensis episcopus, Albertus Pius de Sabaudia, princeps Carporum, Similis, praefectus praetorianorum, Jupiter, Osyris, Isis ; Aeneas Sylvius, Christophorus Colombus, Hermes, Apollo, Timon, Darius ; Robertus Gaguinus, Johannes de Sacro Busto, Darius, Hystaspis filius, Simandius, Aegypti rex, Idomeneus et Myrio, filii Deucalionis, Semiramis ; Alexander Piccolomineus, Justina, pulchra foemina, quam maritus zelotypus nefarie decollavit, Claudia, nobilis foemina Romae, Carolus Magnus, Carolus V, imperator ; Actius Plautus, Johannes Boccacius, Franciscus Ximenes, cardinalis Hispaniae, Federicus imperator, Sylla, Ricardus I, rex Anglorum ; Johannes Stadius, math. belga, C. Manlia camertina, Johannes de Mandeville, Patricius, Brigida et Columda in Hibernia, la reine d'Angleterre, femme de Jacques Ier ; Johannes Glandorp, Jodocus, medicus Romae, Urandus, sive Durandus, Johannes Jacobus Trivultius, Ludovicus VIII, rex Francorum ; Antonius quidam italus, Fin dal Finale, Battistina Senensis, puella elegantissima ; Chalonerus Dubliniae, Askew Lincolniensis, Christophorus Hatton, Robertus, comes Leicestriae ; Johannes Chidley, Walterus Ralegh, Arturus Gorges, Johannes Parkar, Maria Stafford, Charitas et Carolus Ho., Thomas Wals, Sylvanus Scorus, Johannes Horo et Edwardus Nymark, Edwardus Stanhop, Franciscus Wal ; Philippus Sydney, Franciscus Walsinghan, N. Marsonius, jurisconsultus, Christophorus H, Gulielmus, comes Penbrok, Angliae marescallus, Antonius Deny, frater Lubinus ; Fratislaus, dux Bohemiae, countess of Penbrok, Edward Spenser, Henry Abyngdon, Thomas Nash, N. Dobson ; Dr Hugh a price, Johannes Vitulus, Dr Bently, Hor. Pallavicin, Margaret Ratcliff ; Howlet, Elian, Henry Barron ; James Stuart, Thomas Sackville, Penelope d'Evreux, uxor domini Bar. Rich, pellicis comitis Devonshire, Robert Cecil, Ricardus Bancroft, archiepiscopus Cantuariensis ; Godefridus de Bulion, Balduinus, rex Jerusalem, Allicia, pulchra foemina anglica et forte meretrix, Theobaldus, comes Campaniae, qui vixit tempore regis Angliae Stephani ; Fernandus de Castro, hispanus in Anglia exulans et moriens ob fidem in Dominum Petrum, regem Castellae, Johannes Taylor de Colman street, usurarius, Petrus Miago Vallisoleti, in templo Sancti Stephani, Franciscus Duarte de Mendico, a proveedor de los exercitos y armadas del emperador Carlo V, Henricus, Walliae princeps ; Milo, comes de Anglera, pater Rolandi, a Mauris juxta ripam Ceae occisus, Hecuba, S. Edmundus, rex et martyr, Pindarus, poeta lyricus, Stesichorus, Anacreon, poeta vinosus, Leonidas, dux Lacedemoniorum ad Thermopylas occisus contra Persas, Timotheus, citharedus milesius ; Timocreon Rhodius, Laïs, meretrix Corinthia, sepulta in Thessalia, juxta Peneum fluvium, Acron, antiquissimus medicus Agrigentinus

Um exemplo de negação do conceito de elemento na filosofia natural

The focus of this work is to present an example of refutation of the concept of element inside the seventeenth-century scientific revolution, mainly through Robert Boyle’s The Sceptical Chymist. On the first section of this paper the notion of element as considered by the ancient Greeks in Aristotle’s Physics and modern chemists in Paracelsus will be briefly presented. After that in the second section Boyle’s deconstruction of the idea of element will be exposed considering his argumentation of why this notion is prejudicial to the study of nature. Finally, in the third section follows the constructive stage in which a new hypothesis is presented (the corpuscular hypothesis) as the best option to replace the notion of element.

The poetic and dramatic works of Robert Browning.

Half-title; each volume has special t.-p.

Versuch einer Kritik der echtheit der Paracelsischen Schriften

Part 1 is a descriptive list of 518 titles, arranged chronologically.

The early literary career of Robert Browning; four lectures.

From the library of T. L. Hood, with his marginal notes.

Die theaterstücke /

BD. 1. Anatol. Das märchen. Liebelei. Freiwild. 1896. Das vermächtnis.--Bd. 2. Paracelsus. Die gefährtin. Der grüne kakadu. Der schleier der Beatrice. Lebendige stunden.--Bd. 3. Der einsame weg.. Zwischenspiel.. Marionetten. 1902-04. Der ruf des lebens.--Bd. 4. Komtesse Mizzi oder Der familientag. Der junge Medardus. Das weite land.--Bd. 5. Professor Bernhardi. Komödie der Worte. Fink und Fliederbusch. Die Schwestern oder Casanova in Spa.

Historische Darstellungen. Erste Versuche der historischen Gesellschaft zu Jena

Pausanias, von C. F. W. Grosch. --Numantia's Fall, von K. G. Schulze. --Der Krieg der Hunnen gegen die Westgothen und Römer in den Jahren nach Chr. G. 451 u. 52. --Lebensbeschreibung Gottfrieds von Bouillon, von Christian Schubart. --Zur Geschichte des Theophrastus Paracelsus, von Friedrich Amberg. --Philipp Jacob Spener, von F. W. C. Emil Pfranger.

[Complete works of Robert Browning,

"In preparing this first fully annotated edition of the complete works of Robert Browning, care has been taken to give with accuracy the poet's own latest revised text of 1888, 1889 ..."--Editors pref.

Select poems of Robert Browning;

Contains songs from "Paracelsus," and from "Pippa passes," selections from: "Dramatic lyrics," "Dramatic romances," "Men and women," "Dramatis personae," "Pacchiarotto, with other poems," "Dramatic idyls," "Jocoseria" and "Asolando."

The poetic and dramatic works of Robert Browning.

[I] Pauline: Paracelsus: Strafford: Sordello: Pippa passes: King Victor and King Charles.--[II] Dramatic lyrics: The return of the Druses: A blot in the 'scuteheon: Colombe's birthday: Dramatic romances: A soul's tragedy: Luria.--[III] The ring and the book.--[IV] Christmas-eve and Easter day: Men and women: In a balcony: Dramatis peronae: Balaustion's adventure: Prince Hohenstiel-Schwangau: Fifine at the fair.--[V] Red cotton night-cap country: Aristophanes' apology: The inn album: Pacchiarotto and how he worked in distemper, and other poems.--[VI] The Agamemmon of æschylus: La Saisiaz: The two poets of Croisic: Dramatic idyls: Jocoseria: Ferishtah's fancies and parleyings.--[VII] A solando.