Olfactory stem cells reveal MOCOS as a new player in autism spectrum disorders.

With an onset under the age of 3 years, autism spectrum disorders (ASDs) are now understood as diseases arising from pre- and/or early postnatal brain developmental anomalies and/or early brain insults. To unveil the molecular mechanisms taking place during the misshaping of the developing brain, we chose to study cells that are representative of the very early stages of ontogenesis, namely stem cells. Here we report on MOlybdenum COfactor Sulfurase (MOCOS), an enzyme involved in purine metabolism, as a newly identified player in ASD. We found in adult nasal olfactory stem cells of 11 adults with ASD that MOCOS is downregulated in most of them when compared with 11 age- and gender-matched control adults without any neuropsychiatric disorders. Genetic approaches using in vivo and in vitro engineered models converge to indicate that altered expression of MOCOS results in neurotransmission and synaptic defects. Furthermore, we found that MOCOS misexpression induces increased oxidative-stress sensitivity. Our results demonstrate that altered MOCOS expression is likely to have an impact on neurodevelopment and neurotransmission, and may explain comorbid conditions, including gastrointestinal disorders. We anticipate our discovery to be a fresh starting point for the study on the roles of MOCOS in brain development and its functional implications in ASD clinical symptoms. Moreover, our study suggests the possible development of new diagnostic tests based on MOCOS expression, and paves the way for drug screening targeting MOCOS and/or the purine metabolism to ultimately develop novel treatments in ASD.

Sulfanegen sodium treatment in a rabbit model of sub-lethal cyanide toxicity.

The aim of this study is to investigate the ability of intramuscular and intravenous sulfanegen sodium treatment to reverse cyanide effects in a rabbit model as a potential treatment for mass casualty resulting from cyanide exposure. Cyanide poisoning is a serious chemical threat from accidental or intentional exposures. Current cyanide exposure treatments, including direct binding agents, methemoglobin donors, and sulfur donors, have several limitations. Non-rhodanese mediated sulfur transferase pathways, including 3-mercaptopyruvate sulfurtransferase (3-MPST) catalyze the transfer of sulfur from 3-MP to cyanide, forming pyruvate and less toxic thiocyanate. We developed a water-soluble 3-MP prodrug, 3-mercaptopyruvatedithiane (sulfanegen sodium), with the potential to provide a continuous supply of substrate for CN detoxification. In addition to developing a mass casualty cyanide reversal agent, methods are needed to rapidly and reliably diagnose and monitor cyanide poisoning and reversal. We use non-invasive technology, diffuse optical spectroscopy (DOS) and continuous wave near infrared spectroscopy (CWNIRS) to monitor physiologic changes associated with cyanide exposure and reversal. A total of 35 animals were studied. Sulfanegen sodium was shown to reverse the effects of cyanide exposure on oxyhemoglobin and deoxyhemoglobin rapidly, significantly faster than control animals when administered by intravenous or intramuscular routes. RBC cyanide levels also returned to normal faster following both intramuscular and intravenous sulfanegen sodium treatment than controls. These studies demonstrate the clinical potential for the novel approach of supplying substrate for non-rhodanese mediated sulfur transferase pathways for cyanide detoxification. DOS and CWNIRS demonstrated their usefulness in optimizing the dose of sulfanegen sodium treatment.

Rheumajecta and vasolastine in the treatment of rheumatoid arthritis--the results of a placebo-controlled, double-blind trial of a complementary treatment.

The so called "enzymatic preparations" Rheumajecta and Vasolastine (R & V) belong to the complementary treatments. The preparations have been used for many years in the treatment of patients with rheumatic conditions such as rheumatoid arthritis (RA) in the Netherlands and other countries of Europe, although a proper study showing efficacy was never performed. Therefore a double-blind, placebo-controlled, modified cross-over trial during two periods of 3 months was performed in 34 patients with RA. They were allocated at random to R & V or to placebo injections, all intramuscular. After 3 months of therapy each patient could opt for cross-over in the event of lack of subjective improvement. Clinical assessments including Ritchie's articular index, grip strength, the DUTCH-AIMS questionnaire, ESR and CRP were performed. R & V did not prove to be more effective than placebo. No serious side-effects were seen.

[Rheumajecta and Vasolastine treatment of primary fibromyalgia; results of a randomized placebo-controlled double-blind study]. / Behandeling met Rheumajecta en Vasolastine van primaire fibromyalgie; resultaten van een gerandomiseerd, placebo-gecontroleerd, dubbelblind onderzoek.

Rheumajecta and Vasolastine (R and V) are preparations belonging to complementary medicine. They are applied in rheumatic conditions such as primary fibromyalgia. In this double-blind, modified cross-over trial, the effect of R and V injections was compared with that of placebo over two periods of three months in 30 patients with primary fibromyalgia. No significant differences in effectiveness between R and V and placebo were seen. There were no serious side-effects. R and V are not indicated for primary fibromyalgia unless no more effect than that of placebo is intended.

Rheumajecta in the treatment of rheumatoid arthritis.

A double-blind controlled trial of Rheumajecta in rheumatoid arthritis demonstrated lack of effect of this compound and unacceptable side-effects. It was not felt ethically justifiable to complete the trial.