Free energy profiles from single-molecule pulling experiments

Nonequilibrium pulling experiments provide detailed information about the thermodynamic and kinetic properties of molecules. We show that unperturbed free energy profiles as a function of molecular extension can be obtained rigorously from such experiments without using work-weighted position histograms. An inverse Weierstrass transform is used to relate the system free energy obtained from the Jarzynski equality directly to the underlying molecular free energy surface. An accurate approximation for the free energy surface is obtained by using the method of steepest descent to evaluate the inverse transform. The formalism is applied to simulated data obtained from a kinetic model of RNA folding, in which the dynamics consists of jumping between linker-dominated folded and unfolded free energy surfaces.     

Local SAR reduction in parallel excitation based on channel-dependent Tikhonov parameters

Purpose

To reduce the local specific absorption rate (SAR) obtained with tailored pulses using parallel transmission while obtaining homogenous flip angle distributions.

Materials and Methods

Finite‐element simulations on a human head model were performed to obtain the individual magnetic and electric field maps for each channel of a parallel transmit array. From those maps, SAR calculations were carried out for “spoke” pulses designed to homogenize the flip angle in an axial slice of a human brain at 7 T. Based on the assumption that the coil element nearest to the maximum local energy deposition is the dominant contributor to the corresponding hot spot, a set of channel‐dependent Tikhonov parameters is optimized. Resulting SAR distributions are compared to the ones obtained when using standard pulse design approaches based on a single Tikhonov parameter.

Results

In both the small‐ and large‐tip‐angle domain, the simulations show local SAR reductions by over a factor of 2 (4) for a well‐centered (off‐centered) head model at the expense of roughly 1% increment in flip‐angle spread over the slice.

Conclusion

Significant SAR reductions can be obtained by optimizing channel‐dependent Tikhonov parameters based on the relation between coil elements and SAR hot spot positions. J. Magn. Reson. Imaging 2010;32:1209–1216. © 2010 Wiley‐Liss, Inc.     

Estimation of postoperative fat absorption using the <Superscript>13</Superscript>C mixed-triglyceride breath test in children with choledochal cyst

No previous studies have focused on postoperative fat malabsorption in children with choledochal cyst (CC) who undergo cyst excision and Roux-en-Y (RY) hepatico–jejunostomy (HJ), a combination of procedures that can lead to the non-physiological mixture of food and bile juice. To examine the effect of RYHJ with cholecystectomy on the fat absorption ability of children with CC, we estimated postoperative fat-absorption ability using the carbon 13-labeled mixed triglyceride (¹³C-MTG) breath test. Twelve postoperative children with CC and 12 normal control children were administered ¹³C-MTG orally and asked to give breath samples at six time points: once before the ¹³C-MTG ingestion and at five 60-min intervals post-ingestion. Fecal chymotrypsin activity and fecal fat excretion were also measured. The delta value of breath ¹³CO₂ at 3, 4, and 5 h after administration and the 5-h cumulative breath ¹³CO₂ were significantly lower in the CC children than in the controls. There were no significant differences in the fecal chymotrypsin activity or fecal fat excretion of the two groups. Conclusion. Occult fat malabsorption occurs in patients with CC after RYHJ, even in the absence of clinical symptoms or abnormal laboratory data.     

Vitamin B12 Metabolism in Myelomatosis

In 38 patients with myelomatosis the serum cobalamin varied from 34 pmol/l to 404 pmol/l, median 181.5 pmol/l, which is significantly lower than the levels in 22 control persons with range 173–535 pmol/l, median 265 pmol/l. In spite of low serum cobalamin no symptoms of vitamin B₁₂ deficiency could be demonstrated in any of the patients, except for the one patient who had a serum cobalamin of 34 pmol/l. Mean values for Hb, MCV, PCV, serum lactate-dehydrogenase, adjusted red cell folate and nucleated neutrophil count were similar in a group of patients with a serum cobalamin below 160 pmol/l and a group of patients with higher serum cobalamin values. The decrease in serum cobalamin is due in part to a reduction in the major cobalamin binder (TC-I) in serum. Measuring serum cobalamin in relationship to gastric acid secretion, we found a significantly higher frequency of hypo- and achlorhydria in patients with serum cobalamin below 160 pmol/l although the intestinal absorption of vitamin B₁₂ was normal by a Schilling test. Although our finding of low saturation of TC-I in serum seems to demonstrate decreased vitamin B₁₂ content in the body in myelomatosis, the lack of evidence for a functional vitamin B₁₂ deficiency speaks against giving a supplement to patients with myelomatosis.     

UNUSUAL EFFECT OF SOME α-MERCAPTOACRYLIC ACIDS ON METABOLISM OF ZINC IN THE RAT

1. Gavage of rats with β-aryl derivatives of α-mercaptoacrylic acid resulted in pronounced and sustained elevation of serum zinc concentration. Greater than ten-fold increases above normal zinc levels were attained 2–8 h after doses of 50 mg/kg of the phenyl and furan derivatives. 2. These compounds were rapidly absorbed from the rat gastrointestinal tract and could be detected in serum for several days after a single dose. The return of serum zinc concentration to the normal level paralleled clearance of the mercaptoacrylic acid from plasma. 3. Close to 100% of the zinc and of the α-mercapto-β-(2-furan)acrylic acid (MFA) in serum 4 h after administration of the compound were bound to serum macromolecules. 4. MFA decreased excretion of endogenous zinc; it altered neither the gastrointestinal absorption of zinc nor serum concentrations of copper, albumin and total protein. 5. These compounds appear to mobilize zinc from tissue stores and retard zinc clearance from plasma.     

Effect of activated charcoal on absorption and elimination of phenobarbitone,carbamazepine and phenylbutazone in man

Summary The effect of activated charcoal, given as a water suspension, on the absorption and elimination of phenobarbitone 200 mg, carbamazepine 400 mg and phenylbutazone 200 mg, was studied in five healthy volunteers, using a randomized crossover design. Absorption of the drugs was almost completely prevented (more than 95%) when charcoal 50 g was ingested within five minutes of taking the drugs. When activated charcoal was taken one hour after the drugs, the mean inhibition of drug absorption was considerably less and the inhibition was greatly dependent on the individual rate of absorption. The half-life of phenobarbitone was markedly shortened from a control value of 110±23 h to 19.8±1.0 h (P<0.05), with a corresponding increase in plasma clearance from 4.6 ml/min to 23 ml/min, when activated charcoal 118 g, in five divided doses was given between 10 and 48 h after ingestion of the drug. The half-life of carbamazepine was shortened by 45% (P<0.05) and the reduction in the half-life of phenylbutazone (30%) by charcoal, too, was statistically significant. The only side effect from use of the charcoal suspension was constipation, which occured in three subjects after repeated doses, and which was easily treated with lactulose if required. Although activated charcoal should be given as soon as possible, even its delayed use may be indicated, due to the slow absorption often seen in acute intoxication. The use of multiple doses of charcoal appears to be indicated as an additional treatment of certain severe intoxications to prevent the release of drugs from charcoal, and to increase their rate of elimination if they are secreted into the gut with subsequent reabsorption.     

STIMULATION OF SODIUM AND WATER SECRETION WITHOUT INHIBITION OF GLUCOSE ABSORPTION IN THE RAT JEJUNUM BY VASOACTIVE INTESTINAL PEPTIDE (VIP)

1. Infusion of vasoactive intestinal peptide (VIP) into the arterial blood supply of the small intestine in anaesthetized rats did not alter either the perfusion pressure in the superior mesenteric artery or the active absorption of glucose from the jejunum, but did produce a large net secretion of Na⁺ and water into the lumen of the jejunum. 2. The results are compared to the effects of prostaglandin E₁ which stimulates Na⁺ and water secretion and inhibits glucose active absorption in the rat jejunum.     

Mobilization of lead during pregnancy in rats

Summary Increase in urinary excretion of mercury and increase in blood concentration following the use of mercury based drugs has been checked by a limited volunteer study.