Long-term Effect of Bariatric Surgery on the Use of Levothyroxine and Thyroid Levels

BACKGROUND: The aim of this study was to evaluate the effect of bariatric surgery on the defined daily dose of levothyroxine (DDD LT4), thyroid-stimulating hormone (TSH), and free thyroxine (fT4) in female patients with hypothyroidism until 48 months after surgery. METHODS: A retrospective observational study of hypothyroid patients who underwent bariatric surgery. Changes in DDD LT4, TSH, and fT4 over a 48 month period after surgery were analyzed. RESULTS: Thirty-seven patients were included: 27 Roux-en-Y gastric bypass (RYGB), 6 sleeve gastrectomy (SG), 3 adjustable gastric band, and 1 one anastomosis gastric bypass. The median DDD LT4 decreased from 125 µg at baseline to 100 µg 12 months after surgery. From 24 to 48 months after surgery, the median DDD LT4 was stable at 125 µg. Most dose adjustments occurred during the first 24 months after surgery. In the time period of 24-48 months after surgery, the dose remained stable in 73.1% of the RYGB patients and in 60.0% of the SG patients. After 48 months in the RYGB group, no significant change in TSH and fT4 levels was observed. CONCLUSIONS: Bariatric surgery led to frequent dose adjustments during the first 2 years after surgery. However, 24-48 months after surgery in the majority of patients, the dosage remained stable. No significant change in TSH and fT4 was observed 48 months after RYGB. In the first 2 years after surgery, clinicians should frequently monitor TSH and fT4 for individual dose adjustment of levothyroxine. Thereafter, the frequency of monitoring may be decreased

C1 compounds as auxiliary substrate for engineered Pseudomonas putida S12

The solvent-tolerant bacterium Pseudomonas putida S12 was engineered to efficiently utilize the C1 compounds methanol and formaldehyde as auxiliary substrate. The hps and phi genes of Bacillus brevis, encoding two key steps of the ribulose monophosphate (RuMP) pathway, were introduced to construct a pathway for the metabolism of the toxic methanol oxidation intermediate formaldehyde. This approach resulted in a remarkably increased biomass yield on the primary substrate glucose when cultured in C-limited chemostats fed with a mixture of glucose and formaldehyde. With increasing relative formaldehyde feed concentrations, the biomass yield increased from 35% (C-mol biomass/C-mol glucose) without formaldehyde to 91% at 60% relative formaldehyde concentration. The RuMP-pathway expressing strain was also capable of growing to higher relative formaldehyde concentrations than the control strain. The presence of an endogenous methanol oxidizing enzyme activity in P. putida S12 allowed the replacement of formaldehyde with the less toxic methanol, resulting in an 84% (C-mol/C-mol) biomass yield. Thus, by introducing two enzymes of the RuMP pathway, co-utilization of the cheap and renewable substrate methanol was achieved, making an important contribution to the efficient use of P. putida S12 as a bioconversion platform host

Methanol metabolism in thermotolerant methylotrophic Bacillus species

For a number of years we have tried to isolate versatile methylotrophic bacteria employing the ribulose monophosphate (RuMP) cycle of formaldehyde fixation. Recently this has resulted in the development of techniques for the selective enrichment and isolation in pure culture of Bacillus strains able to grow in methanol mineral medium over a temperature range between 35 and 60 °C. At the optimum growth temperatures (50-55 °C), these isolates display doubling times between 40 and 80 min. The metabolism of the strains studied is strictly respiratory. Methanol assimilation is exclusively via the RuMP cycle variants with the fructose bisphosphate (FBP) aldolase cleavage and transketolase (TK)/transaldolase (TA) rearrangement. Whole cells were unable to oxidize formate, and no activities of NAD-(in)dependent formaldehyde and formate dehydrogenases were detected. Formaldehyde oxidation most likely proceeds via the so-called dissimilatory RuMP cycle. The initial oxidation of methanol is catalyzed by an NAD-dependent methanol dehydrogenase present as an abundant protein in all strains. The enzyme from Bacillus sp. C1 has been purified and characterized.

Use of the tac promoter and lacIq for the controlled expression of Zymomonas mobilis fermentative genes in Escherichia coli and Zymomonas mobilis.

The Zymomonas mobilis genes encoding alcohol dehydrogenase I (adhA), alcohol dehydrogenase II (adhB), and pyruvate decarboxylase (pdc) were overexpressed in Escherichia coli and Z. mobilis by using a broad-host-range vector containing the tac promoter and the lacIq repressor gene. Maximal IPTG (isopropyl-beta-D-thiogalactopyranoside) induction of these plasmid-borne genes in Z. mobilis resulted in a 35-fold increase in alcohol dehydrogenase I activity, a 16.7-fold increase in alcohol dehydrogenase II activity, and a 6.3-fold increase in pyruvate decarboxylase activity. Small changes in the activities of these enzymes did not affect glycolytic flux in cells which are at maximal metabolic activity, indicating that flux under these conditions is controlled at some other point in metabolism. Expression of adhA, adhB, or pdc at high specific activities (above 8 IU/mg of cell protein) resulted in a decrease in glycolytic flux (negative flux control coefficients), which was most pronounced for pyruvate decarboxylase. Growth rate and flux are imperfectly coupled in this organism. Neither a twofold increase in flux nor a 50% decline from maximal flux caused any immediate change in growth rate. Thus, the rates of biosynthesis and growth in this organism are not limited by energy generation in rich medium