Human taurine metabolism: fluxes and fractional extraction rates of the gut, liver, and kidneys

Taurine is involved in numerous biological processes. However, taurine plasma level decreases in response to pathological conditions, suggesting an increased need. Knowledge on human taurine metabolism is scarce and only described by arterial-venous differences across a single organ. Here we present taurine organ fluxes using arterial-venous concentration differences combined with blood flow measurements across the 3 major organ systems involved in human taurine metabolism in patients undergoing hepatic surgery. In these patients, we collected blood from an arterial line, portal vein, hepatic vein, and renal vein, and determined blood flow of the hepatic artery, portal vein, and renal vein using Doppler ultrasound. Plasma taurine was determined by high-performance liquid chromatography, and net organ fluxes and fractional extraction rates were calculated. Seventeen patients were studied. No differences were found between taurine concentrations in arterial, portal venous, hepatic venous, and renal venous plasma. The only significant finding was a release of taurine by the portally drained viscera (P = .04). Our data show a net release of taurine by the gut. This probably is explained by the enterohepatic cycle of taurine. Future studies on human taurine metabolism are required to determine whether taurine is an essential aminosulfonic acid during pathological conditions and whether it should therefore be supplemented.     

Genetic variation for stress-response hormesis in C. elegans lifespan

Increased lifespan can be associated with greater resistance to many different stressors, most notably thermal stress. Such hormetic effects have also been found in C. elegans where short-term exposure to heat lengthens the lifespan. Genetic investigations have been carried out using mutation perturbations in a single genotype, the wild type Bristol N2. Yet, induced mutations do not yield insight regarding the natural genetic variation of thermal tolerance and lifespan. We investigated the genetic variation of heat-shock recovery, i.e. hormetic effects on lifespan and associated quantitative trait loci (QTL) in C. elegans. Heat-shock resulted in an 18% lifespan increase in wild type CB4856 whereas N2 did not show a lifespan elongation. Using recombinant inbred lines (RILs) derived from a cross between wild types N2 and CB4856 we found natural variation in stress-response hormesis in lifespan. Approx. 28% of the RILs displayed a hormesis effect in lifespan. We did not find any hormesis effects for total offspring. Across the RILs there was no relation between lifespan and offspring. The ability to recover from heat-shock mapped to a significant QTL on chromosome II which overlapped with a QTL for offspring under heat-shock conditions. The QTL was confirmed by introgressing relatively small CB4856 regions into chromosome II of N2. Our observations show that there is natural variation in hormetic effects on C. elegans lifespan for heat-shock and that this variation is genetically determined.     

No evidence that common genetic risk variation is shared between schizophrenia and autism

The similarity between aspects of the clinical presentation of schizophrenia and autism spectrum disorders (ASD) suggests that elements of the biological etiology may also be shared between these two disorders. Recently, an increasing number of rare, mostly structural genetic variants are reported to increase the risk of both schizophrenia and ASD. We hypothesized that given this evidence for a shared genetic background based on rare genetic variants, common risk alleles may also be shared between ASD and schizophrenia. To test this hypothesis, the polygenic score, which summarizes the collective effect of a large number of common risk alleles, was used. We examined whether the polygenic score derived from a schizophrenia case–control dataset, previously reported by Purcell et al., was able to differentiate ASD cases from controls. The results demonstrate that the schizophrenia‐derived polygenic score is not different between ASD cases and controls, indicating that there is no important sharing of common risk alleles between the two neuropsychiatric disorders. Possibly, common risk alleles are less important in ASD in comparison to their more prominent role in schizophrenia and bipolar disorders. These findings provide important novel insights into shared and distinct elements of the genetic architecture of autism and schizophrenia. © 2012 Wiley Periodicals, Inc.     

Preoperative staging of perforated diverticulitis by computed tomography scanning

Background

Treatment of perforated diverticulitis depends on disease severity classified according to Hinchey’s preoperative classification. This study assessed the accuracy of preoperative staging of perforated diverticulitis by computerized tomography (CT) scanning.

Methods

All patients who presented with perforated diverticulitis between 1999 and 2009 in two teaching hospitals of Rotterdam, the Netherlands, and in addition had a preoperative CT scan within 24?h before emergency surgery were included. Two radiologists reviewed all CT scans and were asked to classify the severity of the disease according to the Hinchey classification. The CT classification was compared to Hinchey’s classification at surgery.

Results

Seventy-five patients were included, 48 of whom (64?%) were classified Hinchey 3 or 4 perforated diverticulitis during surgery. The positive predictive value of preoperative CT scanning for different stages of perforated diverticulitis ranged from 45 to 89?%, and accuracy was between 71 and 92?%. The combination of a large amount of free intra-abdominal air and fluid was strongly associated with Hinchey 3 or 4 and therefore represented a reliable indicator for required surgical treatment.

Conclusions

The accuracy of predicting Hinchey’s classification by preoperative CT scanning is not very high. Nonetheless, free intra-abdominal air in combination with diffuse fluid is a reliable indication for surgery as it is strongly associated with perforated diverticulitis with generalized peritonitis. In 42?% of cases, Hinchey 3 perforated diverticulitis is falsely classified as Hinchey 1 or 2 by CT scanning.     

Biomechanical and rheological characterization of mild intervertebral disc degeneration in a large animal model

Biomechanical properties of healthy and degenerated nucleus pulposus (NP) are thought to be important for future regenerative strategies for intervertebral disc (IVD) repair. However, which properties are pivotal as design criteria when developing NP replacement materials is ill understood. Therefore, we determined and compared segmental biomechanics and NP viscoelastic properties in normal and mildly degenerated discs. In eight goats, three lumbar IVDs were chemically degenerated using chondroitinase ABC (CABC), confirmed with radiography and MRI after euthanasia 12 weeks post‐operative. Neutral zone (NZ) stiffness and range of motion (ROM) were determined sagitally, laterally, and rotationally for each spinal motion segment (SMS) using a mechanical testing device. NPs were isolated for oscillatory shear experiments; elastic and viscous shear moduli followed from the ratio between shear stress and strain. Water content was quantified by weighing before and after freeze‐drying. Disc height on radiographs and signal intensity on MRI decreased (6% and 22%, respectively, p < 0.01) after CABC treatment, confirming that chemical degeneration provides a good model of disc degeneration. Furthermore, CABC‐injected IVDs had significantly lower NZ stiffness and larger ROM in lateral bending (LB) and axial rotation (AR) than controls. Rheometry consistently revealed significantly lower (10–12%) viscoelastic moduli after mild degeneration within goats, though the inter‐animal differences were relatively large (complex modulus ～12 to 41 kPa). Relative water content in the NP was unaffected by CABC, remaining at ～75%. These observations suggest that viscoelastic properties have a marginal influence on mechanical behavior of the whole SMS. Therefore, when developing replacement materials the focus should be on other design criteria, such as biochemical cues and swelling pressure. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 703–709, 2013