Traveling the vitamin B12 pathway: Oral delivery of protein and peptide drugs

Oral routes of administration for therapeutic peptides and proteins face two major barriers: proteolytic degradation in the stomach and an inadequate absorption mechanism for polypeptides within the intestinal lumen. As a result, peptide-based therapeutics are administered by injection, a painful process associated with lower patient compliance. The development of a means of overcoming these two major obstacles and enabling the successful delivery of peptide therapeutics by the oral route of administration has therefore been the target of extensive scientific endeavor. This Minireview focuses on oral peptide/ protein delivery by the dietary uptake pathway for vitamin B 12. Recent progress in this field includes the delivery of erythropoietin, granulocyte-colony-stimulating factor, luteinizing-hormone- releasing hormone, and insulin

Vitamin B12 as a carrier for the oral delivery of insulin

The noninvasive delivery of insulin continues to be a major goal for the treatment of diabetes mellitus. Oral-enteric administration would make insulin delivery easier and more effective, as higher patient compliance and improved glycemic control are likely; yet the oral-enteric pathway has been unfeasible owing to insulin's susceptibility to proteolytic degradation and inefficient enteric uptake. Herein we show that a noninvasive oral delivery route for insulin is possible through the vitamin B12 uptake pathway. In diabetic rat models, insulin-B12 conjugates can significantly lower blood glucose levels when administered orally

The principles of conservation and development: do they apply in Malinau?

Attempts to reconcile economic development with environmental conservation in a forest area in East Kalimantan, Indonesia, are reviewed for the district of Malinau, East Kalimantan, Indonesia, an area of 42,000 km2 that is still largely covered in rainforest. The history of the region is described and the conservation and development impacts of external drivers of change are assessed. Both government and conservation organizations have subscribed to the rhetoric of pursuing development pathways that would be sustainable and would conserve the rich biodiversity of the area. Three distinct approaches to conservation have been attempted. First spatial planning has been used to attribute land to different uses and particularly to identify and designate protected areas. Second, measures have been taken to lessen the negative environmental impact of industrial logging and to promote the preservation of biodiversity in logged forests. Last, decentralized and community-based management has been promoted on the assumption that this would yield better environmental and social outcomes than large-scale industrial development. These conservation measures have been pursued during a period when the governance of the region has been weak. Corruption, political collusion, and nepotism have been major factors in decision making about natural resources. We argue that a sustainable future for the district of Malinau must lie in finding an appropriate balance between protected areas, forests managed at both industrial and community scales, and land conversion. However, there is little empirical evidence that allows the outcomes of these approaches to be measured. The problem of knowing how conservation investments can be made in ways that optimize sustainable benefits to local livelihoods remains largely unresolved. A number of possible conservation and development pathways for the district are discussed

Exploring the implications of vitamin B12 conjugation to insulin on insulin receptor binding

We recently reported a vitamin B12 (B12) based insulin conjugate that produced significantly decreased blood glucose levels in diabetic STZ-rat models. The results of this study posed a fundamental question, namely what implications does B12 conjugation have on insulin's interaction with the insulin receptor (IR)? To explore this question we used a combination of molecular dynamics simulations and immunoelectron microscopy, and the results are described herein. This investigation demonstrates that chemical modification of insulin by linking relatively large pendant groups does not inherently interfere with IR recognition. Furthermore, given that we have previously demonstrated a significant drop in blood glucose concentration following the oral administration of the B12-insulin bioconjugate used in this work, it is reasonable to conclude that the IR recognition described herein is associated with maintenance of biological activity for insulin. This outcome offers significant research scope for chemical modification of insulin with the purpose of improving oral-uptake efficiency

Measuring KS0K± interactions using Pb–Pb collisions at √sNN=2.76 TeV

We present the first ever measurements of femtoscopic correlations between the K0 S and K± particles. The analysis was performed on the data from Pb–Pb collisions at √sNN = 2.76 TeV measured by the ALICE experiment. The observed femtoscopic correlations are consistent with final-state interactions proceeding via the a0(980) resonance. The extracted kaon source radius and correlation strength parameters for K0 SK− are found to be equal within the experimental uncertainties to those for K0 SK+. Comparing the results of the present study with those from published identical-kaon femtoscopic studies by ALICE, mass and coupling parameters for the a0 resonance are tested. Our results are also compatible with the interpretation of the a0 having a tetraquark structure instead of that of a diquar

HΛ3 and H‾Λ‾3 lifetime measurement in Pb–Pb collisions at √sNN=5.02 TeV via two-body decay

An improved value for the lifetime of the (anti-)hypertriton has been obtained using the data sample of Pb–Pb collisions at √sNN = 5.02 TeV collected by the ALICE experiment at the LHC. The (anti-)hypertriton has been reconstructed via its charged two-body mesonic decay channel and the lifetime has been determined from an exponential fit to the dN/d(ct) spectrum. The measured value, τ = 242+34 −38 (stat.) ± 17 (syst.) ps, is compatible with representative theoretical predictions, thus contributing to the solution of the longstanding hypertriton lifetime puzzle