The histopathological changes associated with allograft rejection and drug toxicity in renal transplant recipients maintained on FK506: Clinical significance and comparison with cyclosporine

The histopathological changes in 51 renal allograft biopsies from patients immunosuppressed with FK506 were compared with those seen in 30 needle biopsies obtained from patients on cyclosporine. The frequency and severity of rejection episodes were similar in both groups. Tubular vacuolation and myocyte vacuolation were found to be useful morphological markers to monitor short-term drug toxicity associated with both drugs. Long-term administration of FK506 led to striped interstitial fibrosis and arteriolar hyalinosis, similar to that previously documented for cyclosporine. One case each of hemolytic uremic syndrome and necrotizing arteriopathy was noted in patients receiving FK506. FK506 and cyclosporine are structurally unrelated compounds; hence the parallelism observed in their nephrotoxicity profile suggests that the interactions of these drugs with renal tissue involves the operation of two different initial signal-transducing mechanisms, ultimately activating the same final metabolic pathways

The University of Pittsburgh: a three and three-quarter-year experience with cadaveric renal transplantation under the point system.

Eight hundred and sixty kidney transplants were performed at the University of Pittsburgh over a 3.75-year period between January 1, 1986 and October 19, 1989. Recipient selection was by means of a computerized point system designed to allocate organs equitably. Ninety-three percent 1-year patient survival and 74% 1-year graft survival were obtained in the overall group; 80% 1-year graft survival was obtained in patients receiving immunosuppression with CsA, azathioprine, and prednisone. These data serve as a measure of what can be achieved with an equitably based allocation system and can serve as a basis of comparison with other allocation protocols or new immunosuppressive regimens

Randomized trial of FK 506/prednisone vs FK 506/azathioprine/prednisone after renal transplantation: preliminary report.

FK 506 was used as a primary immunosuppressive agent in 125 cases of renal transplantation in a randomized trial comparing FK 506/prednisone with FK 506/azathioprine/prednisone. With a mean follow-up of 5.5 +/- 2.5 months, there has been a 6-month actuarial patient survival of 99% and graft survival of 88%. There is no difference thus far between the two-drug and three-drug groups, although there may be less rejection and diabetes in the three-drug group. These results suggest that FK 506 is a useful immunosuppressive agent in kidney transplantation

Mechanical measurements of heterogeneity and length scale effects in PEG-based hydrogels.

Colloidal-probe spherical indentation load-relaxation experiments with a probe radius of 3 μm are conducted on poly(ethylene glycol) (PEG) hydrogel materials to quantify their steady-state mechanical properties and time-dependent transport properties via a single experiment. PEG-based hydrogels are shown to be heterogeneous in both morphology and mechanical stiffness at this scale; a linear-harmonic interpolation of hyperelastic Mooney-Rivlin and Boussinesq flat-punch indentation models was used to describe the steady-state response of the hydrogels and determine upper and lower bounds for indentation moduli. Analysis of the transient load-relaxation response during displacement-controlled hold periods provides a means of extracting two time constants τ1 and τ2, where τ1 and τ2 are assigned to the viscoelastic and poroelastic properties, respectively. Large τ2 values at small indentation depths provide evidence of a non-equilibrium state characterized by a phenomenon that restricts poroelastic fluid flow through the material; for larger indentations, the variability in τ2 values decreases and pore sizes estimated from τ2via indentation approach those measured via macroscopic swelling experiments. The contact probe methodology developed here provides a means of assessing hydrogel heterogeneity, including time-dependent mechanical and transport properties, and has potential implications in hydrogel biomedical and engineering applications.The authors would like to acknowledge funding from the National Institutes of Health.This is the author accepted manuscript. The final version is available from the Royal Society of Chemistry via http://dx.doi.org/10.1039/C5SM01210

A winner in the Anthropocene: changing host plant distribution explains geographical range expansion in the gulf fritillary butterfly

1. The changing climate is altering species distributions with consequences for population dynamics, resulting in winners and losers in the Anthropocene. 2. Agraulis vanillae, the gulf fritillary butterfly, has expanded its range in the past 100 years in the western U.S.A. Time series analysis is combined with species distribution modelling to investigate factors limiting the distribution of A. vanillae and to predict future shifts under warming scenarios. 3. Time series analyses from the western U.S.A. show that urban development has a positive association with year of colonisation (the host plant Passiflora is an ornamental in gardens). Colonisation was also associated positively and to a lesser extent with winter maximum temperatures, whereas a negative impact of minimum temperatures and precipitation was apparent on population growth rates after establishment. 4. Species distribution models vary by region. In the eastern U.S.A., the butterfly is primarily limited by minimum temperatures in the winter and host availability later in the season. Eastern U.S. projected expansion broadly follows the expectation of poleward distributional shifts, especially for the butterfly's maximum annual extent. Western U.S. distributions are limited by the host plant, which in turn is dependent on urban centres. Projected western U.S. expansion is not limited to a single direction and is driven by urban centres becoming more suitable for the host plant. 5. These results demonstrate the value of combining time series with spatial modelling, at the same time as incorporating biotic interactions, aiming to understand and predict shifting geographical ranges in the Anthropocene