3-Methylindole (skatole) and indole production by mixed populations of pig fecal bacteria

Pig fecal slurries converted added L-tryptophan either to indole without detectable intermediates or to 3-methylindole (skatole) via indole-3-acetate. The initial rate of production of 3-methylindole was greatest at pH 6.5 and less at pH 5.0 and 8.0; the initial rates of indole production were similar at pH 6.5 and 8.0. More than 80% of the tryptophan added was converted to 3-methylindole at pH 5.0; at pH 8.0 85% was converted to indole. Both pathways had similar Km values for tryptophan and similar maximum rates. Indole-3-carbinol and indole-3-acetonitrile completely inhibited the production of 3-methylindole from indole-3-acetate but had no effect on the reactions involving L-tryptophan.     

Photochemotherapy: identification of a metabolite of 4, 5', 8-trimethylpsoralen

A compound, 4, 8-dimethyl, 5'-carboxypsoralen (DMeCP), has been identified in mouse urine as a major metabolite of the photoactive drug, 4, 5', 8-trimethylpsoralen (TMeP). This drug is widely used in the treatment of vitiligo and psoriasis. DMeCP is fluorescent, and nonphotosensitizing when tested on guinea pig skin. DMeCP also occurs in the urine of human patients receiving TMeP orally.     

A stereological study of substantia nigra in young and old rhesus monkeys

The number of pigmented and non-pigmented neurons in the substantia nigra (SN) of 10 old and six young female Macaca mulatta monkeys and in three old alpha male monkeys were estimated using new stereological cell counting methods. No systematic right-left differences were noted, nor were old animals different from young ones with respect to SN volume (68.9 mm3 vs. 62.8 mm3) or absolute number of nerve cells (320,000 vs. 312,000). However, the total number of pigmented neurons was about eight times higher in old animals compared with young ones (166,000 vs. 21,400) while the total number of non-pigmented SN neurons was less than half in old animals compared with young ones (139,000 vs. 285,000). These differences create difficulties in generalizing experimental results from the rhesus animal model to man. It seems unlikely that a simple correlation can be made between pigmented and tyrosine hydroxylase (TH) positive neurons in SN in monkeys. Instead of estimating the total number of pigmented and non-pigmented cells, only SN neurons positive for TH using immunohistochemical techniques might be used an indicator of the total number of dopaminergic neurons in SN in monkeys.     

Cell-Free Multi-Enzyme Synthesis and Purification of Uridine Diphosphate Galactose

High costs and low availability of UDP-galactose hampers the enzymatic synthesis of valuable oligosaccharides such as human milk oligosaccharides. Here, we report the development of a platform for the scalable, biocatalytic synthesis and purification of UDP-galactose. UDP-galactose was produced with a titer of 48 mM (27.2 g/L) in a small-scale batch process (200 μL) within 24 h using 0.02 g_enzyme/g_product. Through in-situ ATP regeneration, the amount of ATP (0.6 mM) supplemented was around 240-fold lower than the stoichiometric equivalent required to achieve the final product yield. Chromatographic purification using porous graphic carbon adsorbent yielded UDP-galactose with a purity of 92 %. The synthesis was transferred to 1 L preparative scale production in a stirred tank bioreactor. To further reduce the synthesis costs here, the supernatant of cell lysates was used bypassing expensive purification of enzymes. Here, 23.4 g/L UDP-galactose were produced within 23 h with a synthesis yield of 71 % and a biocatalyst load of 0.05 g_{total_protein}/g_product. The costs for substrates per gram of UDP-galactose synthesized were around 0.26 €/g.     

Impact of first-responder defibrillation in an urban emergency medical services system

OBJECTIVE: To evaluate the impact of adding first-responder defibrillation by fire-fighters to an existing advanced life-support emergency medical services system. DESIGN: Nonrandomized, controlled clinical trial with periodic crossover. SETTING: Memphis, Tenn, a city of 610,337 people, which is served by a fire department-based emergency medical services system. All city ambulances provide advanced life support. PATIENTS: Adult victims of out-of-hospital cardiac arrest due to heart disease. INTERVENTION: Twenty of 40 participating engine companies were equipped with an automated external defibrillator and ordered to apply it immediately in all cases of cardiac arrest. The other 20 companies were ordered to start cardiopulmonary resuscitation (CPR) immediately and wait for paramedics to arrive. Every 75 days, group roles were reversed. Care otherwise proceeded according to 1986 American Heart Association guidelines. MAIN OUTCOME MEASURES: Return of spontaneous circulation in the field, survival to hospital admission, survival to hospital discharge, and neurological status at discharge. RESULTS: During the 39-month study interval, 879 patients were treated by a project engine company. Four hundred thirty-one (49%) of these were found in ventricular fibrillation. Bystander CPR was started in only 12% of cases. Overall, firefighters reached the scene a mean of 2.5 minutes faster than simultaneously dispatched paramedics. Although our automated external defibrillators proved to be reliable and efficacious for terminating ventricular fibrillation and pulseless ventricular tachycardia, patients treated by an automated external defibrillator-equipped engine company were no more likely than CPR-treated controls to be resuscitated (32% vs 34%, respectively), to survive to hospital admission (31% vs 29%), or to survive to hospital discharge (14% vs 10%). Neurological outcomes were also similar in the two treatment groups. CONCLUSIONS: In a fast-response, urban emergency medical services system served by paramedics, the impact of adding first-responder defibrillation appears to be small. Early defibrillation alone cannot overcome low community rates of bystander CPR. Careful attention to every link in the "chain of survival" is needed to achieve optimal rates of survival after cardiac arrest.