Oral supplementation of inorganic pyrophosphate in pseudoxanthoma elasticum.

Pseudoxanthoma elasticum (PXE; OMIM 264800) is a rare heritable multisystem disorder, characterized by ectopic mineralization affecting elastic fibres in the skin, eyes and the cardiovascular system. Skin findings often lead to early diagnosis of PXE, but currently, no specific treatment exists to counteract the progression of symptoms. PXE belongs to a group of Mendelian calcification disorders linked to pyrophosphate metabolism, which also includes generalized arterial calcification of infancy (GACI) and arterial calcification due to CD73 deficiency (ACDC). Inactivating mutations in ABCC6, ENPP1 and NT5E are the genetic cause of these diseases, respectively, and all of them result in reduced inorganic pyrophosphate (PPi ) concentration in the circulation. Although PPi is a strong inhibitor of ectopic calcification, oral supplementation therapy was initially not considered because of its low bioavailability. Our earlier work however demonstrated that orally administered pyrophosphate inhibits ectopic calcification in the animal models of PXE and GACI, and that orally given Na4 P2 O7 is absorbed in humans. Here, we report that gelatin-encapsulated Na2 H2 P2 O7  has similar absorption properties in healthy volunteers and people affected by PXE. The sodium-free K2 H2 P2 O7 form resulted in similar uptake in healthy volunteers and inhibited calcification in Abcc6-/- mice as effectively as its sodium counterpart. Novel pyrophosphate compounds showing higher bioavailability in mice were also identified. Our results provide an important step towards testing oral PPi in clinical trials in PXE, or potentially any condition accompanied by ectopic calcification including diabetes, chronic kidney disease or ageing.

Dual Inhibition of Ca(+2) Influx and Phosphodiesterase Enzyme Provides Scientific Base for the Medicinal Use of Chrozophora prostrata Dalz. in Respiratory Disorders.

The crude ethanolic extract of Chrozophora prostrata (Cp.Cr) was tested using in vivo and ex vivo assays for its possible bronchodilatory effects in order to validate its medicinal use in respiratory disorders, like asthma and cough. Cp.Cr exhibited dose-dependent inhibition of carbachol (CCh)-induced bronchospasm in anesthetized rats, similar to aminophylline. When tested on guinea-pig tracheal preparations, Cp.Cr caused relaxation of both CCh (1 µM) and high K(+) (80 mM)-induced contractions with comparable potencies, similar to papaverine, a dual inhibitor of phosphodiesterse (PDE) and Ca(+2) influx. Pre-treatment of the tracheal tissues with Cp.Cr resulted in potentiation of the inhibitory effect of isoprenaline on CCh-induced contractions, like that caused by papaverine indicative of PDE inhibitory activity, which was confirmed when Cp.Cr concentration dependently (1 and 3 mg/mL) increased intracellular cAMP levels of the tracheal preparations, like papaverine. Cp.Cr shifted concentrationresponse curves of Ca(+2) constructed in guinea-pig tracheal preparation towards right with suppression of the maximum response, similar to both verapamil and papaverine. These data indicate bronchodilator activity of Chrozophora prostrata mediated possibly through dual inhibition of PDE and Ca(+2) influx, thus, showing therapeutic potential in asthma with effect enhancing and side-effect neutralizing potential Copyright © 2016 John Wiley & Sons, Ltd.

The therapeutic effect of Tarentula cubensis extract (Theranekron®) in foot-and-mouth disease in cattle: a randomised trial in an endemic setting.

BACKGROUND: Foot-and-mouth disease (FMD) is a contagious viral disease of ruminant animals. Eradication of disease in western countries is by slaughter of infected and in contact animals but this is not possible in endemic countries. There is no standard treatment for FMD in endemic countries, but anti-inflammatory drugs and mild disinfectant and protective dressing to inflamed areas to prevent secondary infection is recommended. METHOD: A randomised controlled clinical trial of a homeopathic preparation of Tarentula cubensis (Theranekron®) was conducted during an outbreak of FMD in cattle in Iran. A single subcutaneous injection of Theranekron® was used as sole treatment in 50 infected animals (treatment group). The control group comprised 15 infected animals treated with standard medication including: daily injection of flunixin meglumine and oxytetracycline and daily dressing of lesions with 4% sodium carbonate. Systemic and local signs were recorded over 14 days. RESULTS: Rectal temperature in treatment group subsided to normal range within 1 day of homeopathic treatment, and was significantly lower in test group than in control group on several successive days (P < 0.05). Healing of inflamed mucosal areas and appetite score of the treatment was significantly better than control during first 3 days of treatment (P < 0.05). CONCLUSION: It appears that Theranekron® is effective for treatment of systemic and local signs of FMD-infected cattle. Further research is justified.

The brown spider Loxosceles laeta: source of the remedy Tarentula cubensis?

The homeopathic remedy Tarentula cubensis (Cuban tarantula), used in homeopathy to treat abscesses with burning pains, gangrene, septicaemia, toxaemia, has been grouped by homeopathic authorities with either the mygalomorph or wolf spiders. The original specimen used for preparation of the mother tincture was decomposed, leaving the spider's exact identity in doubt. Investigation of the toxicological and clinical literature, compared with homeopathic materia medica, reveals the brown spider, Loxosceles laeta, indigenous to South America but present also in Mid- and North America, as a more likely source. Venoms of spiders of the genus Loxosceles cause severe necrotic arachnidism, as well as, in some cases, a life-threatening systemic reaction marked by renal failure, disseminated intravascular coagulation, thrombocytopeania, coma and convulsions.