Horse Chestnut Saponins-Escins, Isoescins, Transescins, and Desacylescins.

Escins constitute an abundant family of saponins (saponosides) and are the most active components in Aesculum hippocastanum (horse chestnut-HC) seeds. They are of great pharmaceutical interest as a short-term treatment for venous insufficiency. Numerous escin congeners (slightly different compositions), as well as numerous regio-and stereo-isomers, are extractable from HC seeds, making quality control trials mandatory, especially since the structure-activity relationship (SAR) of the escin molecules remains poorly described. In the present study, mass spectrometry, microwave activation, and hemolytic activity assays were used to characterize escin extracts (including a complete quantitative description of the escin congeners and isomers), modify the natural saponins (hydrolysis and transesterification) and measure their cytotoxicity (natural vs. modified escins). The aglycone ester groups characterizing the escin isomers were targeted. A complete quantitative analysis, isomer per isomer, of the weight content in the saponin extracts as well as in the seed dry powder is reported for the first time. An impressive 13% in weight of escins in the dry seeds was measured, confirming that the HC escins must be absolutely considered for high-added value applications, provided that their SAR is established. One of the objectives of this study was to contribute to this development by demonstrating that the aglycone ester functions are mandatory for the toxicity of the escin derivative, and that the cytotoxicity also depends on the relative position of the ester functions on the aglycone.

Hemolysis interference on clinical chemistry tests analyzed on DxC 700 AU (Beckman Coulter®) and kaliemia rendering algorithm / Interférence de l'hémolyse sur les examens de biochimie clinique analysés sur DxC 700 AU (Beckman Coulter®) et algorithme de rendu de la kaliémie

The influence of hemolysis was evaluated for 26 clinical chemistry parameters on DxC 700AU (Beckman Coulter®). Ten sample pools were prepared and separated into six aliquots. These aliquots were overloaded with hemolysis in increasing amounts to reach levels equivalent to the maximum hemolysis thresholds H1 (+), H2 (++), H3 (+++) and H4 (++++). Each aliquot is compared to its reference aliquot (not hemolyzed) and a ratio is calculated for each parameter. We proposed that there was a significant difference if, for a given analyte and threshold, more than 20% of the ratios are above the total acceptable limit variability. A significant difference was found for TGP, TGO, cholesterol, creatine kinase (CPK), lactate deshydrogenase (LDH), phosphorus and potassium at H1 (+), chlorine, iron, γ-glutamyltransferase (GGT), and magnesium at H2 (++), amylase and alkaline phosphatase (PAL) at H3 (++++), and prealbumin at H4 (++++). No interference was found until H4 included for uric acid, calcium, creatinine, lipase, glucose, HDL-cholesterol, triglycerides, urea, sodium and immunoglobulins A, G and M. The overestimation of kalemia was calculated as a function of hemolysis, ranging from 0.28 mM +/­0.047 (upper H1 threshold) to 1.37 mM +/­0.126 (upper H4 threshold). Its estimation makes it possible to propose a result rendering algorithm of kalemia according to the hemolysis index. Evaluation of the automates hemolysis indexes is highly recommended for each laboratory. It can allow for some critical parameters the establishment of a decision tree facilitating the result rendering, after clinicobiological consultation.

L'influence de l'hémolyse a été évaluée pour 26 paramètres biochimiques sur l'analyseur DxC 700 AU (Beckman Coulter®). Dix pools d'échantillons ont été préparés et séparés en six aliquots surchargés en hémolysat selon une quantité croissante d'hémoglobine pour atteindre des niveaux équivalents aux seuils maximums d'hémolyse de l'automate H1(+), H2(++), H3(+++) et H4 (++++). Chaque aliquot est comparé à son aliquot de référence (sans hémolysat) et un ratio est calculé pour chaque paramètre. Nous proposons une différence significative si, pour un analyte et un seuil donné, plus de 20 % des ratios sont supérieurs à la variabilité limite totale acceptable (VLTA). Une différence significative est retrouvée pour ALAT, ASAT, cholestérol, créatine kinase (CPK), lactate deshydrogenase (LDH), phosphore et potassium dès H1, chlore, fer, γ--glutamyltransferase (GGT), et magnésium pour H2, amylase et phosphatase alcaline (PAL) pour H3, et préalbumine pour H4. Aucune interférence n'a été retrouvée jusqu'à H4 inclus pour acide urique, calcium, créatinine, lipase, glucose, HDL-cholestérol, triglycérides, urée, sodium et immunoglobulines A, G et M. La surestimation de la kaliémie a été calculée en fonction de l'hémolyse : elle varie de 0,28 mM ± 0,047 (seuil supérieur de H1) à 1,37 mM ± 0,126 (seuil supérieur de H4). Son estimation permet proposer un algorithme de rendu de résultat de la kaliémie selon l'index d'hémolyse. L'évaluation des index d'hémolyses de l'automate est, pour chaque laboratoire, fortement recommandée. Elle peut permettre, pour certains paramètres critiques, la mise en place d'un arbre décisionnel facilitant le rendu de résultat, après concertation clinicobiologique.

[Plague in Marseille: comparison with other plague epidemics in Western Europe]. / La grande peste de Marseille: confrontation avec les autres epidémies de peste en Europe occidentale.

Plague in Marseilles in 1720 is compared with other epidemics in other European cities.

[Jean Reverzy, physician and author in Lyon (1914-1959)]. / Jean Reverzy, médecin et ecrivain lyonnais (1914-1959).

Jean Reverzy (1914-1959) was a general practitioner in Lyons who got a sudden literary fame with his first novel Le Passage. From 1954 to his death he published Place des angoisses (1956), Le Corridor (1958) and Le Silence de Cambridge (1960). In his books a mirror image is always given of Lyons, a city of mist and mystery, but truly memorable remains in the works of Jean Reverzy his unique and very personal experience of medicine, hospitals and patients. A collection of photographs, portraits and auto-portraits has been presented in homage to Jean Reverzy, a physician-writer.

[Portraits of physicians: the past found]. / Portraits de médecins: le passé retrouvé.

Until the 16th Century, physicians had always been portrayed, on paintings, frescoes and statues, as anonymous practitioners. Since that time, a vast amount of portraits has come down to us. In the Library of the Academy of Medicine alone, are registered more than 7000 documents (portraits, photographs, heliographies and caricatures).

[Cancer in antiquity. Lessons of Celsus]. / Le cancer dans i'antiquité. Les enseignements de Celse.

There is mention of "cancer" in many medical texts from Antiquity. An analysis is presented here of a passage from Aulus Cornelius Celsus, De medicina (V 28.2), dealing with cancer and its treatment. A confrontation has been attempted with Ancient texts on this subject and, also, some of the present advances in a new medical speciality: onco-archeology. As depicted by the Ancients, "cancer", very likely, was not different from what we know. All available data suggest that cancer, from the origins of humanity, was present all over the world but there is still no clear answer to the question of an eventual change in cancer frequency over the past 2000 years. A new field of research remains wide open to give answers to this crucial interrogation.

[The three lives of the Count de Bonneval, alias Osman Pasha (1675-1747)]. / Les trois vies du comte de Bonneval alias Osman Pacha (1675-1747).

Count Claude-Alexandre de Bonneval (1675-1747), had a unusual existence: he had three consecutive lives: as an Officer in the Royal Guard of Louis XIV, as Major-General with Prince Emmanuel of Savoy and, finally, as Ottoman Pasha in Constantinople. He was a man of multiple facets: soldier and political adviser, swordsman and world traveller, friend of Casanova, Fenelon, Montesquieu and Leibniz. He was also an inveterate transgressor of every rule and, in the end, a renegade apostate. Many explanations have been offered for his astounding life: plain aristocratic frivolity, emotional instability, and possibly, in reference to a permanent quest for new adventures, countries or religions, a touch of transformism. Obviously, Bonneval concealed, behind a flamboyant personality, some sort of psychiatric fragility which might suggest, in retrospect, a "paranoid syndrome" but, certainly, no trace of what is common in psychopathic patients, a weariness of life. Bonneval loved each one of his three lives and the feeling was mutual.

[Cannabis, hemp and hashish: always returning]. / Cannabis, chanvre et haschich: l'éternel retour.

Cannabis has a long story, the story of an endless return through ages and countries, all over the world. There is no mention of an "hedonist" use of cannabis in Ancient Greek or Roman sources but cannabism is largely attested in Orient as early as in the Middle Ages, even if many tales about Haschishins and Crusaders remain highly controversial. The "come back" of cannabism can be traced back in Europe at the end of XVIIIth century after the Egyptian campaigns of Bonaparte. Thus was launched an increasing vogue of orientalism, soonly after followed by the emergence of cannabism in Paris or London and, half a century later, the United States. After a brief armistice, cannabis rises up again with force at the end of XXth century, all over the world. In our times cannabis remains in the centre of all discussions about hallucinogen substances and many ethical, moral or medical questions are still unanswered. Our final comments will go to the everlasting "come back" of cannabism: search of exotism, attempt to escape from reality or as suggested by recent physiologic studies, close inter-relations between sensorial paths and the upper brainstem centers.

[The autumn crocus: two millenniums of actuality]. / Le colchique: deux millénaires d'actualité.

Colchicum holds a singular place in the History of Medicine. Many names were given through the ages: "ephemera", "finger of Hermes", "pater noster", "tue-chiens". Modern phytonyms clearly refer to the land of Colchis, a mythical place close to Armenia. Several centuries were needed to understand that, despite a frightening reputation, colchic was an elective treatment for the gout. In its long story, appears famous personages as Theophraste, Paulus Aeginata, Gilbertus Anglicus, the baron Storck and Benjamin Franklin. In modern times, colchicum has received besides gout, a wide array of new indications, among others: Behcet disease, collagen diseases and malignancies. A scarcely known chapter of genetics is the findings in 1889, by B. Pernice, an obscure physician from Palermo, of the major mitoic changes observed on gastric and intestinal mucosa of two dogs which had received large doses of colchicum. In spite of their scientific value, the works of Pernice remained largely ignored until 1949. Recent advances in colchiocotheraphy have shown fascinating new fields for research: thus in the familial Mediterranean fever, close to periodic disease, genetic disorder elective for subjects originated from all over Mediterranean and around Black Sea... the mythical country of Colchis. No other medicinal plant than colchic, except poppy, can give such records of perennial use in such a wide range of disorders.

[Mythology and the medicinal plants of antiquity]. / Mythologie et plantes médicinales de l'Antiquité.

In any civilization, nature is closely bound to the world of divinities. This is clearly seen in the Mediterranean world of Antiquity in every reference to the medicinal plants. Our aim, in this study, was to demonstrate the link between mythology and medicine. Through several centuries of medicinal practice, appears a therapeutic knowledge close to become a science. In spite of many gaps, errors and illusions thus emerges a first attempt to master the art of healing. Is it possible to speculate on a new type of drug research guided from ancient texts? Ethnopharmacology investigating medicinal traditions of the world has already obtained in this field some spectacular findings. At the moment, it would be difficult to predict the future of archeopharmacology but as Paul Valery said: "Present is nothing else than a future nutriment for the past".

[Surgery of the spleen in antiquity]. / La chirurgie splénique de l'Antiquité.

Splenic surgery, a common practice in Antiquity? Such a question will appear somewhat provocative despite an ample mention of such facts in Roman and Greek classic literature. This paper intends to explore the large border standing between myths where the spleen keeps a major place and reality which is, on this subject, far from easy to decipher. In final analysis, it seems likely that there had always existed, from the very early ages, some form of splenic cauterisation. The type of procedures reported in the texts cannot be interpreted as variant of the ritual scarifications widely practised until recently in many countries. On the other hand, the idea that physicians, at the time of Antiquity, could perform splenectomy does not seem, in spite of Ancient authors assumptions, to be considered. In fact, there is no direct testimony available on this subject in Latin or Greek medical literature. We suggest that the so-called "splenectomies" of Antiquity could have been surgical "make-believes" closely similar to the quack practices which can be yet observed in some remote countries.