Natural Ergot Alkaloids in Ocular Pharmacotherapy: Known Molecules for Novel Nanoparticle-Based Delivery Systems.

Several pharmacological properties are attributed to ergot alkaloids as a result of their antibacterial, antiproliferative, and antioxidant effects. Although known for their biomedical applications (e.g., for the treatment of glaucoma), most ergot alkaloids exhibit high toxicological risk and may even be lethal to humans and animals. Their pharmacological profile results from the structural similarity between lysergic acid-derived compounds and noradrenalin, dopamine, and serotonin neurotransmitters. To reduce their toxicological risk, while increasing their bioavailability, improved delivery systems were proposed. This review discusses the safety aspects of using ergot alkaloids in ocular pharmacology and proposes the development of lipid and polymeric nanoparticles for the topical administration of these drugs to enhance their therapeutic efficacy for the treatment of glaucoma.

Brote de "pie de festuca" en un rodeo de cría de Salta, Argentina / Outbreak of fescue foot in a livestock in Salta, Argentina

Festuca arundinacea es una gramínea perenne de uso forrajero muy difundida mundialmente. Aquí se describe un brote de “pie de festuca” en el Noroeste Argentino que afectó a un rodeo de cría con una incidencia del 5%. Los signos clínicos fueron claudicación, edema en los miembros, gangrena en las extremidades y exungulación. La pastura donde los animales permanecían correspondía a un lote naturalizado de festuca siendo el nivel de infestación con Neotyphodium coenophialum del 71%. El cuadro de pie de festuca es muy conocido pero poco informado en Argentina. En el brote el diagnostico se confirmó por los antecedentes clínicos y epidemiológicos sumado al elevado grado de infestación del hongo en la pastura. La toxicidad de la festuca es un problema mundialmente distribuido y en Argentina ha sido más estudiado en la región centro del país. Los antecedentes de toxicidad de esta especie son escasos y aislados en el Noroeste Argentino.

Festuca arundinacea is a perennial grass which use as forage is widespread worldwide. This report describes a “fescue foot” outbreak in the Northwest of Argentina. Beef cattle herd were affected and the incidence was 5%. The clinical signs were claudication, edema in the limbs, gangrene in the extremities and exungulation. The grazing areas where the animals remained corresponded to a natural batch of fescue. Neotyphodium coenophialum infestation level was 71%. The clinical presentation of fescue root is well described but barely reported in Argentina. In the outbreak presented here diagnosis was confirmed by the clinical and epidemiological antecedents as well as the high level of infestation of the pasture. The toxicity of fescue is a worldwide distributed problem. In Argentina, the disease is well known in the central region of the country. Scarce information is available regarding the toxicity of this species for northwestern Argentina.

Ergot Alkaloids at Doses Close to EU Regulatory Limits Induce Alterations of the Liver and Intestine.

An increase in the occurrence of ergot alkaloids (EAs) contamination has been observed in North America and Europe in recent years. These toxins are well known for their effects on the circulatory and nervous systems. The aim of this study was to investigate the effect of EAs on the liver and on the intestine using the pig both as a target species and as a non-rodent model for human. Three groups of 24 weaned piglets were exposed for 28 days to control feed or feed contaminated with 1.2 or 2.5 g of sclerotia/kg, i.e., at doses close to EU regulatory limits. Contaminated diets significantly reduced feed intake and consequently growth performance. In the liver, alteration of the tissue, including development of inflammatory infiltrates, vacuolization, apoptosis and necrosis of hepatocytes as well as presence of enlarged hepatocytes (megalocytes) were observed. In the jejunum, EAs reduced villi height and increased damage to the epithelium, reduced the number of mucus-producing cells and upregulated mRNA coding for different tight junction proteins such as claudins 3 and 4. In conclusion, in term of animal health, our data indicate that feed contaminated at the regulatory limits induces lesions in liver and intestine suggesting that this limit should be lowered for pigs. In term of human health, we establish a lowest observed adverse effect level (LOAEL) of 100 μg/kg body weight (bw) per day, lower than the benchmark dose limit (BMDL) retained by European Food Safety Authority (EFSA) to set the tolerable daily intake, suggesting also that regulatory limit should be revised.

Simultaneous separation of ergot alkaloids by capillary electrophoresis after cloud point extraction from cereal samples.

A new and sensitive analytical methodology for ergot alkaloids (EA) determination from cereal samples based on cloud point extraction (CPE) prior to CE-UV absorbance was developed. The methodology involves extraction under acid conditions and subsequent preconcentration by applying a simple, rapid and environmentally friendly low volume surfactant extraction procedure. After extraction, CE analysis was carried out by performing dilutions on preconcentrated surfactant rich phase, achieving a single peak or simultaneous alkaloids determination. A real preconcentration factor of 22 of total EA was obtained, demonstrating the efficiency of this methodology. The limits of detection were 2.6 and 2.2 µg/kg for ergotamine and ergonovine, respectively. Validation procedure revealed suitable linearity, accuracy and precision. The average extraction and clean-up recoveries were compared with the theoretical values and were better than 92%. This method was successfully applied to the determination of EA in different varieties of commercial flour samples, two grain samples and one of the leading brands cereal-based product for infant feeding. The high sensitivity achieved for EA determinations in real samples suggests CPE procedure as an interesting approach to improve CE-UV visible detection limits. Moreover, the whole process could be considered as a contribution to green chemistry because nonorganic solvents were involved, demonstrating its great potential over conventional techniques.

The obstetrical use in ancient and early modern times of Convolvulus scammonia or Scammony: another non-fungal source of ergot alkaloids?

PIP: This brief historical survey documenting the use of ergot alkaloids throughout Ancient times for obstetrical purposes (labor induction and control of uterine hemmorrhage) takes its data from works of Theophrastus (who wrote Enquiry into Plants around 300 B.C.), Pliny, Dioscorides, and others. What this history documents is another source for the ergot besides the fungus Clavicips purpurea; notations from Greek, Mexican, and English catalogers show that the family Convolvulaceae is a constant source of ergot alkaloids; this family is the home of Rivea corymbosa, the morning glory seed used by Mexican Indians for both medicinal and religious purposes. In addition, an argument made from salient quotations from historical texts indicates that Scammony may also contain ergot alkaloids, although such compounds have yet to be chemically isolated. Only 1 extant study intimates the possible existence of ergot-like activity in Scammony, a study which showed that small doses of an ether extract of Scammony resin stimulated an isolated guinea pig uterus. If Scammony does contain ergot alkaloids, it is suggested that it will be an excellent source for this material, since the plants cultivation is inexpensive and easy.^ieng

[Syndrome of amenorrhea and galactorrhea. Clinical considerations]. / Sindrome de amenorréa y galactorréa. Consideraciones clínicas.

PIP: Of 180 cases of secondary amenorrhea and 20 of primary amenorrhea, 46 patients suffered from the syndrome of amenorrhea and galactorrhea. This showed that this problem is more frequent than the literature indicates. Of the 46 cases, 13% had a pituitary tumor. Such a high percentage was found with several authors so the possibility of a tumor should always be considered. Another 24% of the cases were postpartum and 52.1% were idiopathic. The latter, suffering from primary or secondary sterility were treated with different ovulation induction medication and in 37.2% pregnancy resulted. In general, the treatment of amenorrhea and galactorrhea tries to restore normal ovulation and the menstrual cycle. Possible useful medications are clomiphene, citrate, pergonal, and levo-dopa. Also, recent studies indicate that some alkaloid derivitives of ergot are effective in treating the syndrome. It is important to realize that the syndrome may have physiopathogenic implications that substantiate careful ovulation induction medication.^ieng

[Functional therapeutics: official subject in gynecology. New findings in gynecology. 22nd Brazilian Meeting on Gynecology and Obstetrics]. / 22 Jornada Brasileira de Ginecologia e Obstetricia, tema oficial de ginecologia; Aquisicoes Recents em Ginecologia: Terapeutica Funcional.

PIP: During the past 5 years, after a much longer period of studies and research, new methods of treatment for several gynecological disorders have been employed. Among such new methods the most important are: 1) the use of gonadotropin-releasing hormones as contraceptive agents, to diagnose cases of hypogonadism, or to cure amenorrhea. Gonadotropin-releasing hormones can be administered in several ways, provoke different reactions in different women, and are subject to several contraindications; 2) transphenoidal surgery for hypersecretory hypophysary tumors, or microsurgery of the hypophysis, which allows the identification of tumors smaller than 10mm, and which is used in the treatment of galactorrhea; 3) the use of ergot alkaloids derivates, such as bromocriptine or Lergotrile, to provoke menstruation and ovulation; 4) the clinical use of danazol in the treatment of endometriosis and in induction of ovulation; and 5) the treatment of primary dysmenorrhea by the use of synthetic inhibitors or by the use of prostaglandins.^ieng