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Evolutionary ecology of the tropane alkaloids of Datura stramonium L. (Solanaceae).

Shonle I, Bergelson J.

Department of Ecology and Evolution, University of Chicago, Illinois 60637, USA.

Although insect herbivory is frequently assumed to be responsible for the maintenance of plant secondary metabolites such as alkaloids, the assumption is controversial and experimental evidence for this assumption is sparse. We examined natural selection on the two major alkaloids present in the leaves of Datura stramonium and found that both alkaloids came under active selection. We found negative directional selection for scopolamine (natural selection acting to reduce scopolamine levels) and stabilizing selection for hyoscyamine (natural selection acting to maintain an intermediate level of hyoscyamine). We also present evidence that insect herbivores act as the agents of selection on these alkaloids. Finally, we show that there were no trade-offs in resistance to different species of insects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10937252&dopt=Abstract hyoscyamine Levbid SL



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Simultaneous determination of scopolamine, hyoscyamine and littorine in plants and different hairy root clones of Hyoscyamus muticus by micellar electrokinetic chromatography.

Mateus L, Cherkaoui S, Christen P, Oksman-Caldentey KM.

Laboratory of Pharmaceutical Analytical Chemistry, University of Geneva, Switzerland.

Hyoscyamus muticus hairy root clones were established following infection with Agrobacterium rhizogenes strains A4, LBA-9402 and 15834 and with A. tumefaciens strain C58C1pRTGus104. The accumulation of tropane alkaloids hyoscyamine, littorine and scopolamine was evaluated by micellar electrokinetic capillary electrophoresis. Littorine was reported for the first time in these clones as well as in the roots of the intact plant and confirmed by collision induced dissociation-mass spectrometry. Tropane alkaloid content in hairy roots was compared with leaves and roots of normal plants at two vegetative stages. Significant differences appeared between the alkaloid contents of the different clones. In particular, all the hairy root clones and the roots of the intact plant produced 1.5-3 and 4.5-9 times more littorine than scopolamine, respectively. The only exception was clone KB7, carrying the h6h gene, which overproduced scopolamine. The aerial parts of H. muticus plants did not contain any littorine, thus indicating different transportation or translocation mechanisms of the various tropane alkaloids.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10939356&dopt=Abstract hyoscyamine Levbid SL



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Effects of the rol C gene on hairy root: induction development and tropane alkaloid production by Atropa belladonna.

Bonhomme V, Laurain-Mattar D, Fliniaux MA.

Laboratoire de Pharmacognosie et Phytotechnologie, Faculte de Pharmacie, 1 Rue des Louvels, 80037 AMIENS, Cedex, France. Valerie.Bonhomme sa.u-picardie.fr

Two series of Atropa belladonna hairy root lines were obtained, the first one transformed via Agrobacterium tumefaciens harboring rol C and npt II genes, and the other transformed with rol ABC and npt II genes. Thirteen hairy root lines were obtained and selected on hormone-free medium. The transformation was confirmed by PCR analysis, and these root lines were first examinated for their growth rate. Then hyoscyamine and scopolamine production was measured after 3 and 4 weeks of culture to evaluate the possible role of rol C gene in tropane alkaloid formation. The rol C gene alone played a significant role in the hairy root growth rate (17-fold increase). However this effect was much lower than that induced by the rol ABC genes together (75-fold increase). In contrast, the rol C gene alone was as efficient as the rol ABC genes together (mean value of total alkaloids: 0.36% dry weight, i.e., 12-fold times more than in untransformed roots) to stimulate the biosynthesis of tropane alkaloids in A. belladonna hairy root cultures.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11000029&dopt=Abstract hyoscyamine Levbid SL



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Irritable Bowel Syndrome.

Wald A.

University of Pittsburgh Medical Center, Pittsburgh University Hospital, Mezzanine Level, C-Wing, 200 Lothrop Street, Pittsburgh, PA 15213-2582.

I believe there are four essential elements in the management of patients with irritable bowel syndrome (IBS): to establish a good physician-patient relationship; to educate patients about their condition; to emphasize the excellent prognosis and benign nature of the illness; and to employ therapeutic interventions centering on dietary modifications, pharmacotherapy, and behavioral strategies tailored to the individual. Initially, I establish the diagnosis, exclude organic causes, educate patients about the disease, establish realistic expectations and consistent limits, and involve patients in disease management. I find it critical to determine why the patient is seeking assistance (eg, cancer phobia, disability, interpersonal distress, or exacerbation of symptoms). Most patients can be treated by their primary care physician. However, specialty consultations may be needed to reinforce management strategies, perform additional diagnostic tests, or institute specialized treatment. Psychological co-morbidities do not cause symptoms but do affect how patients respond to them and influence health care-seeking behavior. I find that these issues are best explored over a series of visits when the physician-patient relationship has been established. It can be helpful to have patients fill out a self-administered test to identify psychological co-morbidities. I often use these tests as a basis for extended inquiries into this area, resulting in the initiation of appropriate therapies. I encourage patients to keep a 2-week diary of food intake and gastrointestinal symptoms. In this way, patients become actively involved in management of their disease, and I may be able to obtain information from the diary that will be valuable in making treatment decisions. I do not believe that diagnostic studies for food intolerances are cost-effective or particularly helpful; however, exclusion diets may be beneficial. I introduce fiber supplements gradually and monitor them for tolerance and palatability. Synthetic fiber is often better-tolerated than natural fiber, but must be individualized. In my experience, excessive fiber supplementation often is counterproductive, as abdominal cramps and bloating may worsen. Antidiarrheal agents are very effective when used correctly, preferably in divided doses. I use them in patients in anticipation of diarrhea and especially in those who fear symptoms when engaged in activities outside the home. I encourage patients to make decisions as to when and how much to use. However, almost always, a morning dose before breakfast is used (loperamide, 2 to 6 mg) and, perhaps again later in the day when symptoms of diarrhea are prominent. I prefer antispasmodics to be used intermittently in response to periods of increased abdominal pain, cramps, and urgency. For patients with daily symptoms, especially after meals, agents such as dicyclomine before meals are useful. For patients with infrequent but severe episodes of unpredictable pain, sublingual hyoscyamine often produces rapid relief and instills confidence. In general, I recommend that oral antispasmodics be used for a limited period of time rather than indefinitely, and generally for periods of time when symptoms are prominent. For chronic visceral pain syndromes, I recommend small doses of tricyclic antidepressants. These agents are especially effective in diarrhea-predominant patients with disturbed sleep patterns but may be unacceptable to patients with constipation. I educate patients that side effects occur early and benefits may not be apparent for 3 to 4 weeks. I consider using SSRIs in low doses in patients with constipation-predominant IBS; cisapride, 10 to 20 mg three times per day, also may be beneficial. When taken with drugs that inhibit cytochrome P450, cisapride has been associated with serious cardiac arrhythmias caused by QT prolongation, including ventricular arrhythmias and torsades de pointes. These drugs include the azole fungicides; erythromycin, clarithromycin, and troleandomycin; some antidepressants; HIV protease inhibitors; and others. In patients with IBS with mild to moderate co-morbid depression, I have found that the use of SSRIs such as paroxetine, fluoxetine, or sertraline may be beneficial. It is important to tell patients that anxiety and disturbed sleep may occur during the first 10 days and benefits may not occur for 3 to 4 weeks. I prescribe a small amount of a short-acting benzodiazepine such as alprazolam, 0.5 mg two times per day, to control these symptoms. For generalized anxiety without depression, buspirone or clonazepam may be useful. I have found that patients who also have associated panic disorder may benefit from a benzodiazepine, tricyclic antidepressant, or an SSRI. However, these patients are best managed in conjunction with a psychiatrist or psychologist. I consider the use of alternative therapies in patients who fail to respond to conventional measures and who are receptive to alternative strategies. These include general relaxation techniques such as biofeedback and hypnosis therapies.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11096567&dopt=Abstract hyoscyamine Levbid SL



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Treatment of elderly women with urge incontinence in middle tennessee: a single institution practice-based study.

Grossklaus DJ, Franke JJ.

Department of Urologic Surgery, Vanderbilt University School of Medicine, Nashville, USA.

INTRODUCTION AND OBJECTIVES: Urinary urge incontinence (UUI) is a major factor in reducing quality of life in elderly women. The treatment of UUI in the elderly population is complicated by comorbidities, polypharmacy, cost, and side effects. The purpose of this study was to examine our practice pattern in Middle Tennessee for the treatment of elderly women with UUI. METHODS: We retrospectively reviewed the medical records of all women over age 65 seen at our institution between January 1, 1998 and September 1, 1999 with an initial complaint of pure UUI. Diagnosis was based on history and physical examination by a single urologist (JJF). Initial treatment in all patients was medication as well as timed and double voids. Medication chosen was based on cost factors, co-morbidities, current medications, and outcome from previous treatment. RESULTS: Of 53 women ranging in age from 65-87 years of age (avg. 74.7) included in this study, 6/53 (11.3%) had a previous CVA, and 2/53 (3.7%) had grade I-II cystoceles. Initial pharmacologic treatment included anticholinergic medication in 47 patients (88.6%), and either imipramine or topical estrogen alone in the remaining 11.4%. Of the anticholinergics, hyoscyamine time capsules were used in 29, tolterodine in 7, standard oxybutynin in 5, oxybutynin XL in 1, and a combination with imipramine in 5. Thirty-four of the 53 total patients (64.1%) discontinued their medications because of no improvement 14 (41.1%), dry mouth 9 (26.4%), other side effects 9 (26.4%), cost 1, and other reasons in the remaining 2 patients. Only 17 patients (32%) stated they were doing well on their initial medications; 11 of those (64.7%) were taking hyoscyamine time capsules. Upon subjective failure, 22/36 patients (61.1%) had their medications changed, while 14/36 (38.8%) pursued behavioral therapy without additional medications. Urodynamic studies were done in 12 patients who failed empiric medical treatment (22.6%). CONCLUSIONS: Only 32% of elderly women treated medically for UUI were satisfied and continued therapy in this patient population. One-fourth of elderly women failed empiric medical management of UUI due to lack of efficacy, and one-third due to intolerable side effects. In this practice, hyoscyamine was continued more often than any other anticholinergic because of reasonable cost, efficacy, and side effect profile.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11117074&dopt=Abstract hyoscyamine Levbid SL