Digitalin

Steroidal glycosides with antiproliferative activities from Digitalis trojana.[Pubmed:23722601]

Phytother Res. 2014 Apr;28(4):534-8.

The phytochemical investigation of Digitalis trojana led to the isolation of two cardiac glycosides (1, 2), one pregnane glycoside (3), three furostanol type saponins (4-6), along with three cleroindicins (7-9), four phenylethanoid glycosides (10-13), two flavonoids (14, 15) and two phenolic acid derivatives (16, 17). The structure elucidation of the isolates was carried out by NMR experiments as well as ESI-MS. The cytotoxic activity of compounds 1-13 against a small panel of cancer cell lines, namely MCF-7, T98G, HT-29, PC-3, A375 and SH-SY5Y, was investigated. Compounds 1-6 showed antiproliferative activity against human breast MCF-7 and colon HT-29 cancer cell lines with IC50 values ranging from 8.3 to 50 muM. In order to understand the mechanism involved in the cell death, the active compounds were tested as pro-apoptotic agents using propidium iodide staining by flow cytometry method. No significant increase was observed in the apoptosis of the MCF-7 and HT-29 cancer cells. Moreover, the effects of the active compounds on cell proliferation were assessed on the same cancer cell lines by cell cycle analysis of DNA content using flow cytometry. No significative changes were observed in the cell cycle of MCF-7, while significant changes in G2 /M cell cycle phase of HT-29 cells were observed after treatment with Digitalin (1), cariensoside (3) and 22-O-methylparvispinoside B (6) at 10 muM.

Treprostinil: new drug. Pulmonary artery hypertension: just another (disappointing) prostacycline analogue.[Pubmed:17128524]

Prescrire Int. 2006 Oct;15(85):177-9.

(1) Standard treatment for pulmonary artery hypertension usually combines a calcium channel blocker with an anticoagulant, supplemental oxygen, a Digitalin and a diuretic, with only limited efficacy. When added to this standard treatment, long-term continuous intravenous epoprostenol (prostacycline) infusion improves survival time and quality of life in patients with severe primary pulmonary artery hypertension, but at a cost of many adverse effects, some of which can be serious. Bosentan, an endothelin receptor antagonist, is an oral alternative. (2) Following the approval of inhaled iloprost, another prostacycline analogue, treprostinil, has been approved for use as a continuous subcutaneous infusion. (3) Its clinical evaluation is based on 2 randomised double-blind placebo-controlled trials with disappointing clinical results: the 6-minute walking distance increased by only 10 meters after 12 weeks of treatment. This modest degree of improvement in an intermediate outcome is unlikely to translate into a tangible improvement in quality of life. (4) The only available comparison with epoprostenol is a clinical pharmacology study in about 20 patients, with no tangible clinical benefit. (5) The adverse effect profile of treprostinil is the same as that of epoprostenol, and is mainly due to its vasodilatory properties (diarrhoea, ankle swelling). In addition, pain and other local reactions are very frequent at the point of infusion. (6) Treprostinil must be administered as a continuous subcutaneous infusion; this is not convenient, but it is easier to set up than central intravenous epoprostenol infusion.

Acenocoumarol and vasculitis: a case report.[Pubmed:16981216]

Pharmacoepidemiol Drug Saf. 2007 Jan;16(1):113-4.

A 62-year-old woman was referred to the dermatology department for a history of fever, asthenia and cutaneous rash, which appeared after a 3-day course of Digitalin and acenocoumarol for atrial fibrillation. The physical examination revealed multiple round confluent purpuric lesions over her entire legs with no blistering. Laboratory exams were all negative. Biopsy of the involved skin was compatible with leucocytoclastic vasculitis. The acenocoumarol treatment was withheld and the skin lesions resolved spontaneously over the next 10 days. The cause of this purpura was seemingly acenocoumarol because of the close temporal relationship between exposure to the drug and the onset of the symptoms, and the spontaneous resolution of the lesions after acenocoumarol was discontinued. This observation illustrates a rare association between vasculitis and acenocoumarol. Clinicians should be aware of this potential adverse effect and recommend interrupting the drug intake when temporal relation is evocative.

[Cardiac manifestations of Takayasu's arteritis: apropos of 5 cases].[Pubmed:10422139]

Rev Med Interne. 1999 Jun;20(6):476-82.

PURPOSE: Cardiac manifestations of Takayasu's arteritis are rarely reported in the literature. However, these symptoms are not rare and when they do occur, they determine the disease prognosis. Due to its frequency, its severe nature, and even sometimes diagnosis failure, high blood pressure is the major cause of cardiac manifestations. More specific cardiac manifestations of either coronary, valvular, or more rarely, myocardial origin may also occur. METHODS: Analysis of five cases of Takayasu's arteritis and a literature review allowed evaluation of both the frequency and characteristics of this disease. RESULTS: Four female and one male patients presenting with symptoms of Takayasu's arteritis, according to Fiessinger's score, were evaluated. Diagnosis of cardiac disease was based on clinical, echocardiographic and angiographic criteria. Four patients had related high blood pressure. Valvular manifestations were present in all the patients. They included mitral insufficiency (1 case); aortic insufficiency (2 cases), and both mitral and aortic insufficiency (2 cases). Two patients showed clinical manifestations of a myocardiac disease, and another showed coronary signs. Treatment did not involve surgery, including only antihypertensive drugs, nitrites, and diuretics associated with Digitalin in case of cardiac failure. The disease outcome, including a 5-18 year follow-up, involved symptom decrease in all the patients. CONCLUSION: Despite the rarity of cardiac manifestations in patients suffering from Takayasu's arteritis, symptoms of this disease should always be investigated, as these manifestations alter the prognosis. Aortic insufficiency is the most frequently encountered cardiac manifestation.

[Natriuretic factors].[Pubmed:1604157]

Rev Prat. 1992 Feb 15;42(4):407-11.

Atrial natriuretic factor is the main natriuretic hormone. It is a peptide secreted by the atria in response to an increase of the central blood volume. Its effects are opposed to those of the renin angiotensin system and all result in the decrease of volemia. The main of them are an increase in renal sodium excretion, decrease in vascular resistance, increase in capillary permeability, and inhibition of renin and aldosterone secretions. ANF stimulates, via its B receptors, the production of cyclic GMP which is its second messenger. ANF is catabolized by clearance receptors which internalize it and ectoenzymes, mainly neutral endoproteinase. Plasma ANF increases in various conditions for three essential reasons: increase of its secretion from the usual sources, increase of its secretion from supplementary sites, decrease of its catabolism. Since ANF is implied in the maintenance of homeostasis in several diseases, treatment by neutral endoproteinase inhibitors which increases plasma ANF has been considered. Another natriuretic factor structurally close to Digitalin and inhibiting Na(+)-K+ ATPase has been described but not identified.

[Treatment of patients with acute digitalis poisoning by charcoal hemoperfusion].[Pubmed:3433730]

Vutr Boles. 1987;26(5):46-50.

10 patients with acute digitalis intoxication were treated by charcoal hemoperfusion. The patients had taken high toxic and lethal doses of digitalis drugs: 3 patients had taken 10 mg of (Digitalin, 2 patients--7.5 mg of digoxin, 5 patients--10-25 mg of isolanid (ceglunat). 4 of the patients were with a heart disease and the other 6 patients did not have any heart disease. The charcoal hemoperfusion lasted 4 to 6 hours, in one female patient--2 hours. The mean minute volume was 100 to 150 ml/min, in some patients it reached up to 200 ml/min. The digoxin blood concentration was determined before and after the hemoperfusion in 4 patients and a decrease of 49% was found. 9 patients fully recovered and only one patient, a 70 years old women, who had not received antiarrhythmic treatment, died. Good results were also achieved in Digitalin intoxications determined by the clinical course and the electrocardiographic data. The overall estimation of the method is that it is efficient and should be applied to patients with acute digitalis intoxication, always in combination with antidote, antiarrhythmic and cardioprotective treatment.

Preparation and experimentation of an antidigitalin monoclonal antibody: interest in human treatment.[Pubmed:6526144]

Dev Biol Stand. 1984;57:343-7.

A monoclonal antiDigitalin antibody was obtained following the immunization of BALB/mice with Digitalin coupled to BSA, and the fusion of lymphocytes from these mice with murin myeloma 8653. The supernatants were screened by a radioimmunoassay in which the supernatant was incubated with Digitalin coupled to I125. This monoclonal antibody "Dig 278" has an antigen binding ratio of 95%; is an IgGl; has a titre of 1/1000 and its affinity constant, as determined by a Scatchard plot, was 1,20(9) L/M. By experimenting with the monoclonal antibodies on 15 rabbits, we have obtained the reversal of heart rhythm disorders and the survival of animals injected with a lethal dose of Digitalin. All the controls died. This antibody could prove useful in treating advanced cases of Digitalin intoxication and for which no satisfactory treatment is available at present.

[Production of an anti-digitalin monoclonal antibody (author's transl)].[Pubmed:6807500]

C R Seances Acad Sci III. 1982 Mar 8;294(10):421-4.

Anti-Digitalin monoclonal antibodies were obtained by hybridization of lymphoid cells from mice immunized with the drug and the 8653 myeloma cells from BALB/c Mice. Two of these antibodies were submitted to immunochemical analysis which revealed that they belonged to IgM and IgGl classes, and the high affinity of one of them (1,2 x 10(9) M(-1)). The availability os such antibodies opens new perspectives for the treatment of Digitalin intoxication and the possibility of establishing a standardized radioimmunoassay.