Chlorpropamide-induced hypoglycemia: successful treatment with diazoxide

A healthy adolescent boy was treated on two occasions for an overdose of chlorpropamide (Diabinese). Glucose therapy alone was not sufficient to control the hypoglycemia, but the administration of glucose plus diazoxide raised the blood sugar to supranormal levels. A bolus of intravenous glucagon briefly raised the blood sugar level to within normal limits, increased the blood ketones but also augmented insulin secretion. An overdose of sulfonylurea may cause prolonged and fatal hypoglycemia. Rational therapy, both in diabetic and normal persons, is glucose plus an "insulin antagonist." The administration of diazoxide was effective in our patient, substantially reducing the plasma insulin level; this agent may be the "insulin-antagonist" of choice for use in sulfonylurea-induced hypoglycemia.     

First evidence of grass carp recruitment in the Great Lakes Basin

We use aging techniques, ploidy analysis, and otolith microchemistry to assess whether four grass carp Ctenopharyngodon idella captured from the Sandusky River, Ohio were the result of natural reproduction within the Lake Erie Basin. All four fish were of age 1 +. Multiple lines of evidence indicate that these fish were not aquaculture-reared and that they were most likely the result of successful reproduction in the Sandusky River. First, at least two of the fish were diploid; diploid grass carp cannot legally be released in the Great Lakes Basin. Second, strontium:calcium (Sr:Ca) ratios were elevated in all four grass carp from the Sandusky River, with elevated Sr:Ca ratios throughout the otolith transect, compared to grass carp from Missouri and Arkansas ponds. This reflects the high Sr:Ca ratio of the Sandusky River, and indicates that these fish lived in a high-strontium environment throughout their entire lives. Third, Sandusky River fish were higher in Sr:Ca ratio variability than fish from ponds, reflecting the high but spatially and temporally variable strontium concentrations of southwestern Lake Erie tributaries, and not the stable environment of pond aquaculture. Fourth, Sr:Ca ratios in the grass carp from the Sandusky River were lower in their 2011 growth increment (a high water year) than the 2012 growth increment (a low water year), reflecting the observed inverse relationship between discharge and strontium concentration in these rivers. We conclude that these four grass carp captured from the Sandusky River are most likely the result of natural reproduction within the Lake Erie Basin.     

Micropuncture studies of glucose transport in the dog: mechanism of renal glycosuria

Clearance and micropuncture studies were performed in 23 dogs without glucose loading to examine the tubule mechanism of renal glycosuria. Studies were carried out in three groups of animals before and after 10% extracellular volume expansion, and administration of maleic acid in low dose at 150 mumol/kg and in high dose at 300 mumol/kg. Specific hexokinase methods were used for the determination of glucose in tubule fluid and urine. Under control conditios, glucose reabsorption occurred predominantly in the proximal tubule. In all three groups, proximal tubule reabsorption of both sodium and glucose was inhibited in the second phase, showing a good correlation between the two. In contrast, fractional urinary glucose excretion remained unchanged after volume expansion and low-dose maleic acid, indicating reabsorption of virtually all the increased glucose load at a further "distal" site. On the other hand, significant glycosuria developed after high-dose maleic acid that was a result of reduced glucose reabsorption in the distal nephron, in addition to the proximal effect. It was concluded that distal glucose transport plays a significant role in regulating urinary glucose excretion and maintains renal thershold for glucose,     

Changes in serum thyrotropin (TSH) in man during halofenate administration

Halofenate, a serum lipid-lowering agent which inhibits binding of thyroid hormone to thyroxine-binding globulin (TBG), was administered daily for 14 days to 8 hypothyroid subjects with elevated TSH concentrations as a result of incomplete thyroxine (T4) therapy. Drug administration resulted in mean increases in serum dialyzable fraction T4 (DFT4) of 52% over pretreatment levels (P less than 0.01) and in dialyzable fraction triiodothyronine (DFT3) of 26% in 7 subjects, (P less than 0.01). During halofenate treatment in these 7 subjects, serum TSH concentrations decreased significantly (mean = 39%, P less than 0.01) when DFT4 and DFT3 were increased by halofenate. In only two subjects was there a convincing temporal relationship between increased serum absolute free T4 (AFT4) and decreased serum TSH concentrations. Contrary to what would be predicted from the "free hormone hypothesis", changes in serum TSH concentration in these hypothyroid patients appeared to relate primarily to changes in the free fraction of circulating T4 and T3 (DFT4, DFT3), rather than to alterations in AFT4 or AFT3. Halofenate did not alter serum TBG binding capacity. An eighth subject did not show increased DFT4 and DFT3 during halofenate treatment despite achievement of therapeutic serum levels of the agent; in this patient, serum TSH levels rose progressively throughout the period of inadequate T4 replacement and halofenate administration. In hypothyroid patients, short-term halofenate use suggests that the pituitary-thyroid hormone feedback circuit can respond to increases in serum DFT4 and DFT3 in the absence of detactable increases in absolute free hormone concentrations.     

Multipurpose modular experimental station for the DiProI beamline of Fermi@Elettra free electron laser

We present a compact modular apparatus with a flexible design that will be operated at the DiProI beamline of the Fermi@Elettra free electron laser (FEL) for performing static and time-resolved coherent diffraction imaging experiments, taking advantage of the full coherence and variable polarization of the short seeded FEL pulses. The apparatus has been assembled and the potential of the experimental setup is demonstrated by commissioning tests with coherent synchrotron radiation. This multipurpose experimental station will be open to general users after installation at the Fermi@Elettra free electron laser in 2011.     

The influence of altruism on influenza vaccination decisions

Game theory is based on the assumption that individuals act according to self-interest and make decisions that maximize their personal payoffs. To test this fundamental assumption, we conducted a survey study in the context of influenza vaccination decisions. Contrary to the assumption of self-interest, we found that altruism plays an important role in vaccination decisions. Nevertheless, altruistic motivation has not yet been considered in epidemiological models, in predictions of vaccination decisions or in the design of vaccination policies. To determine the impact of altruism on the adherence to optimal vaccination policies and on resulting disease burden, we incorporated altruism into a game-theoretic epidemiological model of influenza vaccination. We found that altruism significantly shifted vaccination decisions away from individual self-interest and towards the community optimum, greatly reducing the total cost, morbidity and mortality for the community. Therefore, promoting altruism could be a potential strategy to improve public health outcomes.     

The two-regime method for optimizing stochastic reaction–diffusion simulations

Spatial organization and noise play an important role in molecular systems biology. In recent years, a number of software packages have been developed for stochastic spatio-temporal simulation, ranging from detailed molecular-based approaches to less detailed compartment-based simulations. Compartment-based approaches yield quick and accurate mesoscopic results, but lack the level of detail that is characteristic of the computationally intensive molecular-based models. Often microscopic detail is only required in a small region (e.g. close to the cell membrane). Currently, the best way to achieve microscopic detail is to use a resource-intensive simulation over the whole domain. We develop the two-regime method (TRM) in which a molecular-based algorithm is used where desired and a compartment-based approach is used elsewhere. We present easy-to-implement coupling conditions which ensure that the TRM results have the same accuracy as a detailed molecular-based model in the whole simulation domain. Therefore, the TRM combines strengths of previously developed stochastic reaction–diffusion software to efficiently explore the behaviour of biological models. Illustrative examples and the mathematical justification of the TRM are also presented.     

Origin and Regionality of Wines—the Role of Molecular Spectroscopy

The origin of wine has an important relevance not only in relation to the sustainability of the production systems but also in relation to wine quality, having great impact in terms of the economy of small producer. Terms such as protected geographical status (PGS), protected designation of origin (PDO), protected geographical indication (PGI) and traditional speciality guaranteed (TSG) are been used to characterise wines from different regions and countries. Despite the number of papers and reports published in the literature in relation to issues such as authenticity and discrimination in wine, few reports can be found that explore the use of molecular spectroscopy to specifically target denomination of origin. This report reviews the use of molecular spectroscopy to address such issues within the wine industry.     

Modular and Versatile Spatial Functionalization of Tissue Engineering Scaffolds through Fiber‐Initiated Controlled Radical Polymerization

Native tissues are typically heterogeneous and hierarchically organized, and generating scaffolds that can mimic these properties is critical for tissue engineering applications. By uniquely combining controlled radical polymerization (CRP), end‐functionalization of polymers, and advanced electrospinning techniques, a modular and versatile approach is introduced to generate scaffolds with spatially organized functionality. Poly‐ε‐caprolactone is end functionalized with either a polymerization‐initiating group or a cell‐binding peptide motif cyclic Arg‐Gly‐Asp‐Ser (cRGDS), and are each sequentially electrospun to produce zonally discrete bilayers within a continuous fiber scaffold. The polymerization‐initiating group is then used to graft an antifouling polymer bottlebrush based on poly(ethylene glycol) from the fiber surface using CRP exclusively within one bilayer of the scaffold. The ability to include additional multifunctionality during CRP is showcased by integrating a biotinylated monomer unit into the polymerization step allowing postmodification of the scaffold with streptavidin‐coupled moieties. These combined processing techniques result in an effective bilayered and dual‐functionality scaffold with a cell‐adhesive surface and an opposing antifouling non‐cell‐adhesive surface in zonally specific regions across the thickness of the scaffold, demonstrated through fluorescent labelling and cell adhesion studies. This modular and versatile approach combines strategies to produce scaffolds with tailorable properties for many applications in tissue engineering and regenerative medicine.