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The remedies proposed for the prevention and treatment of the plague by the Medical Faculty of Paris and by Joannes de Vesalia are mainly derived from plants and animals apart from some minerals used in medieval medicine. Alchemical preparations, absent in the Compendium, are rarely mentioned by Joannes de Vesalia. About 90% of the simples preconized by the Faculty of Paris are still used as remedies in the tractates of Joannes de Vesalia and Montanus. The development of chemistry in the 16th and 17th centuries is responsible for the introduction of 'chemical' medicines in therapy. Montanus accepts these remedies with some reserve but favours also amulets and magic drugs. The plethora of medicines proposed demonstrates the inefficacy of therapeutics.

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A review of the recent progress in the study of the mode of action of the sennosides, the active constituents of the senna drug, is presented. An interaction between rhein anthrone, the active metabolite of the sennosides, and the immune cells of the colon is suggested as a base for laxative activity.

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The 12th of July 1635, Jan van Beverwyck wrote a letter from Dordrecht to his esteemed friend Luis Nunez, in Antwerp. He asked him for indications about the cure of kidney stones of which he was suffering. He had just passed two calculi very painfully. Nunez answered on July 31. His letter summarized his own experience with this disease. In such cases, temperate diuretics and emollients are well indicated: ingestion of light decoctions of Malva and Viola, Caerefolium and Parieteria as well as Marshmallow syrup. No purge and no 'chemicals'. However, the best remedy was drinking Spa water. Usually the best way to absorb it is to come to the springs, in the Ardennes, part of the independent Principality of Liège. However, considering the horrors of the war (the Thirty Years War) endangering the country, van Beverwyck would be wise to drink imported water during 40 or 50 days, while staying home quietly, in Dordrecht. The letter points out the importance of provoked diuresis in the treatment of kidney stones. On the other hand the letter is an illustration of the continuing contacts between the United Provinces and the Spanish territories and of the commercial traffic between Antwerp, Dordrecht and Spa. The exported water was bottled from many 'pouhons'. It was acid, ferruginous, sulfurous and saturated with carbon dioxide; no pathogen germs, at least at the spring. Nunez quoted the large number of his patients cured with Spa water in Antwerp. This is an illustration of its commercial expansion even during this critical period.

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A review of the recent progress in the study of the mode of action of the sennosides, the active constituents of the senna drug, is presented. An interaction between rhein anthrone, the active metabolite of the sennosides, and the immune cells of the colon is suggested as a base for laxative activity.

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This study used a large, obsessive- compulsive disorder (OCD) population (N = 157) without comorbidity, and compared them to the general population of the States of New York on the following demographic variables: sex ratio, age of onset, age first seen, marital status, occupation, birth trauma, substance abuse, religion, past psychiatric treatment, and parents' psychiatric history. A 1: 1 sex ratio with a significant gender difference was found for age of onset (females = 20.8; males = 16.3 years), and for age first seen (females = 26.4; males 20.3 years). Other significant findings were the following: More single male OCD patients, fewer widowed female patients, more white-collar workers, less drug abusers, more alcohol abstainers, and less non-problem drinkers as compared to the general population. Significantly also, more atheist/agnostic OCD patients were found as compared to other patients. For the first time, the findings can be evaluated against a comparative group.

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This study used a large, obsessive- compulsive disorder (OCD) population (N = 157) without comorbidity, and compared them to the general population of the States of New York on the following demographic variables: sex ratio, age of onset, age first seen, marital status, occupation, birth trauma, substance abuse, religion, past psychiatric treatment, and parents psychiatric history. A 1: 1 sex ratio with a significant gender difference was found for age of onset (females = 20.8; males = 16.3 years), and for age first seen (females = 26.4; males 20.3 years). Other significant findings were the following: More single male OCD patients, fewer widowed female patients, more white-collar workers, less drug abusers, more alcohol abstainers, and less non-problem drinkers as compared to the general population. Significantly also, more atheist/agnostic OCD patients were found as compared to other patients. For the first time, the findings can be evaluated against a comparative group.

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The influence of rhein anthrone on the peristaltic reflex was studied with a modified Trendelenburg technique in the range from 10(-8) to 4 x 10(-5) mol/l, using a normal and reversed guinea pig ileum segment. Rhein anthrone had no significant effects on longitudinal muscle tension, intraluminal pressure or volume displacement when tested on the normal segment in doses up to 10(-5) mol/l. When applied to the mucosal side (reversed segment), rhein anthrone produced a dose-dependent increase of longitudinal muscle tension, of intraluminal pressure and of volume displacement. The data show that rhein anthrone possesses in vitro activity which is dependent on contact with the mucosa. The action of rhein anthrone on the reversed segment was inhibited by BW755C (a dual inhibitor of cyclo-oxygenase and lipoxygenase), by indomethacin and by SC19220 (an antagonist of PGE2 and PGF2 alpha). It is concluded that arachidonic acid metabolites, especially PGE2 and PGF2 alpha are involved in the effects of rhein anthrone on the reversed segment.

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1 The influence of rhein anthrone on the peristaltic reflex was studied with a modified Trendelenburg technique in a range from 10(-8) M to 4 x 10(-5) M, on a normal and reversed guinea-pig ileum segment. Rhein anthrone had no significant effects on longitudinal muscle tension, intraluminal pressure or volume displacement when tested on the normal segment in doses up to 10(-5) M. When applied to the mucosal side (reversed segment), rhein anthrone produced a dose-dependent increase of longitudinal muscle tension (significant from 10(-7) M), of intraluminal pressure (significant from 3 x 10(-6) M) and of volume displacement (significant from 10(-7) M). The data show that rhein anthrone possesses in vitro activity which is dependent on contact with the mucosa. 2 The action of rhein anthrone on the reversed segment was inhibited by BW755C (a dual inhibitor of cyclo-oxygenase and lipoxygenase), by indomethacin and by SC19220 (an antagonist of prostaglandin E2 (PGE2) and PGF2 alpha). The effects remaining on longitudinal muscle tension, intraluminal pressure and volume displacement, calculated as percentage (mean +/- s.e.mean) of the initial value, were respectively: 13 +/- 8; 23 +/- 13; 112 +/- 5 for BW755C; 66 +/- 19; 51 +/- 8; 53 +/- 8 for indomethacin and 27 +/- 12; 13 +/- 7; 50 +/- 5 for SC19220. It is concluded that arachidonic acid metabolites, especially PGE2 and PGF2 alpha are involved in the effects of rhein anthrone on the reversed segment.

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The present study was undertaken to investigate the role of prostaglandins in the shortening of transit time observed after intraduodenal administration of rhein anthrone and rhein. After intraduodenal administration of rhein anthrone (0.5-10 mg/rat), a dose-dependent acceleration of small intestinal transit was observed. The effect for rhein (1-10 mg/rat) was far less pronounced. In the same test conditions, analysis of small intestinal tissue revealed a significant increase of prostaglandin E2 (PGE2), reaching its maximum value 30 min after administration of rhein anthrone. The increase in PGE2 found 30 min after administration of rhein was not significant. The effects provoked by rhein anthrone could be largely prevented by pretreatment of the animals with indomethacin (1-3 mg rat) or cortisol (10 mg/rat). It is concluded that prostaglandins play an important role in the acceleration of the transit provoked in rats by rhein anthrone.

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The effect of rhein and rhein anthrone on the transit and the transport of water and electrolytes in the large intestine was investigated in germ-free rats. After intracaecal administration, neither of the two compounds was found to accelerate the transit of a colour marker through the large intestine. Both drugs reduced the net absorption of sodium and chloride in the colon and enhanced net potassium secretion. Net water absorption was decreased by rhein and even reversed into net secretion by rhein anthrone. Our results show that the secretagogue activity of the compounds is not sufficient to induce laxation in germ-free rats. Furthermore rhein and rhein anthrone had no laxative properties under our experimental conditions.

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The influence of the intestinal microbial reduction of rhein anthraquinone on the formation of deterioration products was studied. Therefore [14C]rhein and [14C]rhein anthrone were mixed with sterilized or non-sterilized cecal mass of rats and incubated for 20 hours at 37 degrees C. Extractions with a methanol-water (50:50) mixture or 4-nitroso-N,N-dimethylaniline (0.1%) in pyridine revealed several radioactive derivatives after TLC and autoradiography, except in the case where the anthraquinone was mixed with sterilized cecal content. Gel permeation on a styrene-divinylbenzene copolymer column of an methanol/water extract of non-sterilized cecal content incubated with [14C]rhein, showed radioactive deterioration products with a molecular weight higher than rhein anthraquinone. The high molecular weight of some deterioration products was confirmed by an ultrafiltration study where the methanol/water extract was centrifuged on a Centricon-3 microconcentrator (nominal cutoff: 3000 MW). Aqueous extracts of non-sterilized cecal content incubated with rhein were extracted with chloroform to remove rhein anthraquinone, rhein anthrone and sennidins before being intracecally injected in rats. No laxative activity was found. Furthermore it was shown that the deterioration products which are probably formed through radical reactions, no longer develop a color with a solution of KOH. Therefore it is concluded that the reduction process of dihydroxy-anthraquinones in the gut microflora followed by an extraction, accounts for the loss of anthranoid equivalents in in vivo circumstances, as several times reported in the past.

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A sensitive spectrofluorimetric method is described to determine small quantities of prostaglandin E2 in complex biological systems as intestinal tissues. The method is based on a solid phase extraction combined with a coupling with a fluorescent marker and measuring the derivatization product by fluorescence densitometry. After mixing the tissue with an ice-cold perchloric acid solution, adjusting the pH, centrifugation and filtration steps, the prostaglandins are retained on a solid phase extraction C18 disposable column. They are eluted with diethylether, derivatized with 4-bromomethyl-7-methoxy-coumarin using potassium carbonate as condensating agent and finally analysed using fluorescence densitometry on silica gel TLC plates. Applying this method, amounts down to 5 ng (per gram wet tissue) could be measured in intestinal tissues, the s.e.m. for replicated total analysis being less than 15%. The foregoing method is applied for the determination of PGE2 released in the intestinal wall under the influence of laxatives.

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Bianthraquinone glycosides are formed during the preparation and conservation of fluid extracts of cascara. Analysis of these preparations has shown that up to 20% of total amount of anthracene glycosides can be dimerized. These dimers are devoid of laxative activity. They are absorbed in the intestine and very slowly excreted.

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The present study was undertaken to investigate the involvement of prostaglandins in the secretagogue action, observed after intraduodenal administration of rhein anthrone and rhein in rats. After intraduodenal administration of rhein anthrone (50 mg/kg), the active metabolite of sennosides, a very marked increase of secretion was observed compared to control. The amount of secretion was calculated by dividing the total weight of the small intestine, obtained 30 minutes after administration of the drug, by the total length. The effect seen with rhein (50 mg/kg) is far less pronounced than that with rhein anthrone and is not significant when compared with control. Pretreating the animals with indomethacin (15 mg/kg, p.o., 1 hour in advance) or with ibuprofen (15 mg/kg, p.o., 1 hour in advance) largely prevents the secretagogue effect of rhein anthrone, suggesting that prostaglandins play an important role in the observed pharmacological action. This idea is reinforced by the observation that pretreatment with hydrocortisone (50 mg/kg, p.o., 6 hours in advance) is also able to counteract the effect of rhein anthrone. After administration of rhein anthrone, an almost tenfold increase of the tissue content of prostaglandin E2 was observed. Here again, the results with rhein were far less pronounced. It is concluded that prostaglandins play an important role in the secretagogue action of rhein anthrone.

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We can distinguish four periods in the iconography of the cocaplant, namely the prehispanic period in South-America, the early period in Europe, from 1749 until 1860, the period of confusion (1860-1906) and finally the period of modern iconography. The iconography of the cocaplant before the arrival of the Spanish invaders was limited to the drawing of cocaleaves. In Europe, the first people who showed any interest for the cocaplant were the botanists. In the second half of the XVIIIth century, the botanists made especially good drawings of Erythroxylum coca. From the second half of the XIXth century, the industry became interested in coca and, consequently, a very intensive research arose, coming from several directions. This led to the discovery of new species, at that time often described by non botanists. This resulted in discussions and in serious confusion as to the nomenclature. Excellent pictures were however produced in this period. During the XXth century fundamental botanical research resulted in the final classification of the different coca species. The quality of the pictures was however not better.

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