A Digital Therapeutic Allowing a Personalized Low-Glycemic Nutrition for the Prophylaxis of Migraine: Real World Data from Two Prospective Studies.

Migraine is a headache disorder associated with a high socioeconomic burden. The digital therapeutic sinCephalea provides an individualized low-glycemic diet based on continuous glucose measurement and is intended to provide a non-pharmacological migraine prophylaxis. We performed two prospective studies with migraine patients who used sinCephalea over a period of 16 weeks. The patients used a headache diary and recorded their migraine-related daily life impairments using the assessment tools HIT-6 and MIDAS for a pre versus post comparison. In addition, continuous glucose data of patients were compared to healthy controls. In both studies, patients reported a reduction of headache and migraine days as well as reductions in HIT-6 and MIDAS scores. More specifically, migraine days decreased by 2.40 days (95% CI [-3.37; -1.42]), HIT-6 improved by 3.17 points (95% CI [-4.63; -1.70]) and MIDAS by 13.45 points (95% CI [-22.01; -4.89]). Glucose data suggest that migraine patients have slightly increased mean glucose values compared to healthy controls, but drop into a glucose range that is below one's individual standard range before a migraine attack. In conclusion, sinCephalea is a non-pharmacological, digital migraine prophylaxis that induces a therapeutic effect within the range of pharmacological interventions.

Oral exposure to inorganic arsenic: evaluation of its carcinogenic and non-carcinogenic effects.

Inorganic arsenic, which is extensively metabolised in humans into even more toxic methylated arsenicals, is a potent carcinogen, causing tumours of the skin, lung, urinary bladder, and other organs. It also induces a number of non-cancer effects. Consumption of drinking water highly contaminated by arsenic causes serious health problems in some countries in southeastern Asia, and arsenic poses problems for drinking-water safety world-wide. Existing risk assessments are based on epidemiological studies from regions with high exposure concentrations (in the mg/L range). It is a matter of debate whether these findings are useful at predicting arsenic-induced effects at low concentrations. In recent years numerous epidemiological studies on cancer and non-cancer effects of inorganic arsenic have been published. This work aims at reviewing recent toxicological and epidemiological data on inorganic arsenic with emphasis on effects at low exposure concentrations. Information obtained from epidemiological studies is supplemented with mechanistic data from in vitro and in vivo studies. Various modes of action for arsenic carcinogenicity are discussed. The information gathered was used to evaluate the reliability of existing cancer-risk assessments and to improve current assessments of non-cancer health effects. A tolerable daily dose, based on epidemiological studies on arsenic-induced skin disorders, is presented.

Tetrathiomolybdate in the treatment of acute hepatitis in an animal model for Wilson disease.

BACKGROUND/AIMS: Tetrathiomolybdate (TTM) is a potent copper-chelating agent that has been shown to be effective in Wilson disease patients with neurological symptoms. Here, we investigate the potential use of TTM in treating the acute hepatic copper toxicosis in Long-Evans Cinnamon (LEC) rats, an authentic model for Wilson disease. METHODS: After the onset of acute hepatitis, LEC rats were treated once with 10 mg TTM/kg. After 1 and 4 days, parameters of liver toxicity and the subcellular distribution and binding of copper and iron were studied. RESULTS: In 11 out of 12 rats TTM rapidly improved acute hepatitis. Hepatic copper decreased through removal from cytosolic metallothionein and lysosomal metallothionein polymers. The remaining lysosomal copper forms a metallothionein-copper-TTM complex. In an almost moribund rat, however, TTM caused severe hepatotoxicity with fatal outcome. CONCLUSIONS: TTM is effective in treating acute hepatitis in LEC rats when applied before the animals become moribund. TTM appears to act by removing the presumable reactive copper associated to lysosomal metallothionein polymers. The remaining lysosomal copper seems to be inactivated by forming a complex with TTM. Moreover, TTM removes copper from cytosolic copper-containing metallothionein. As a consequence, metallothionein is degraded and the uptake of copper-metallothionein into the lysosomes and the formation of the metallothionein polymer associated copper is reduced.