RESUMO
BACKGROUND: Automatic eating detection (AED) can potentially support treatments that need to be synchronized with food intake. This article analyzes an implantable AED device working in conjunction with gastric stimulation intended to treat type 2 diabetes (T2DM). The device continuously senses for changes in tissue impedance and electrical activity induced by food intake and initiates treatment sessions upon detection. This article reviews AED performance as well as its relevance to treatment outcomes. METHODS: Obese T2DM (n = 12) were implanted with gastric leads and the TANTALUS device. An AED algorithm was embedded in the device and was used to initiate periods of electrical stimulation during food intake. AED performance was assessed using patients' food diaries. The treatment outcome at 37 weeks postimplants was correlated with the rates of stimulation during large meals vs stimulation during periods of no caloric intake. RESULTS: The algorithm was able to detect 73% of meals consumed while sensing. The rate of false stimulations was 28%. Stimulation during meals was significantly correlated (R(2) = 0.45, p < 0.05) with hemoglobin A1c change (average drop in hemoglobin A1c was -1 +/- 0.4%) but not with changes in body weight (average drop -4.7 +/- 2.8 kg). Stimulation during periods with no caloric intake was negatively correlated with hemoglobin A1c reduction (R(2) = 0.27, p < 0.05). CONCLUSIONS: Sensing of gastric activity can be used for detection of food intake. The synchronization of gastric stimulation to periods of food intake is correlated with metabolic outcomes. AED may also benefit other applications such as drug delivery and control of food restriction devices.
RESUMO
A series of 2-, 3- and 4-substituted pyridines was metabolised using the mutant soil bacterium Pseudomonas putida UV4 which contains a toluene dioxygenase (TDO) enzyme. The regioselectivity of the biotransformation in each case was determined by the position of the substituent. 4-Alkylpyridines were hydroxylated exclusively on the ring to give the corresponding 4-substituted 3-hydroxypyridines, while 3-alkylpyridines were hydroxylated stereoselectively on C-1 of the alkyl group with no evidence of ring hydroxylation. 2-Alkylpyridines gave both ring and side-chain hydroxylation products. Choro- and bromo-substituted pyridines, and pyridine itself, while being poor substrates for P. putida UV4, were converted to some extent to the corresponding 3-hydroxypyridines. These unoptimised biotransformations are rare examples of the direct enzyme-catalysed oxidation of pyridine rings and provide a novel synthetic method for the preparation of substituted pyridinols. Evidence for the involvement of the same TDO enzyme in both ring and side-chain hydroxylation pathways was obtained using a recombinant strain of Escherichia coli (pKST11) containing a cloned gene for TDO. The observed stereoselectivity of the side-chain hydroxylation process in P. putida UV4 was complicated by the action of an alcohol dehydrogenase enzyme in the organism which slowly leads to epimerisation of the initial (R)-alcohol bioproducts by dehydrogenation to the corresponding ketones followed by stereoselective reduction to the (S)-alcohols.
