Renal safety of a tenofovir-containing first line regimen: experience from an antiretroviral cohort in rural Lesotho

Introduction

Current guidelines contraindicate TDF use when creatinine clearance (CrCl) falls below 50 ml/min. We report prevalence of abnormal renal function at baseline and factors associated with abnormal renal function from a community cohort in Lesotho.

Methods

We calculated changes in CrCl from baseline for patients initiated on TDF at 6 and 12 months and the proportion of patients initiated on TDF who developed renal impairment. Screening algorithms were developed using risk factors determined by multivariate analysis.

Results

Among 933 adults for whom baseline creatinine was available, 176 (18.9%) presented with a baseline CrCl <50 ml/min. Renal function improved during follow-up. 19 patients who developed renal toxicity during follow up remained on TDF; renal function improved (CrCl≥50 ml/min) in all but 3 of these patients. Among 15 patients with a baseline CrCl <50 ml/min were started in error, none developed severe renal impairment.

Conclusion

In this setting TDF-associated renal toxicity is rare and mainly transient. Further studies to assess TDF safety at lower CrCl thresholds are warranted.     

Existence of atrial natriuretic peptide in choroid, retina and ciliary body in rabbits]

The presence of atrial natriuretic factor (ANF) in choroid, retina and ciliary body of rabbit eyes has been studied. The peptide was extracted by reverse phase chromatography using Sep-Pak C18 cartridges. Immunoreactive ANF (Ir-ANF) was measured by a specific RIA. In the choroid, retina and ciliary body the ir-ANF concentrations were 444 +/- 94, 67 +/- 12 and 223 +/- 75 pg/g tissue weight (n = 16), respectively. The biological activity of the acid extract ANF was evaluated by a 125I-ANF binding assay to a retinal particulate preparation. Results demonstrate the existence of biological active ANF in choroid, retina and ciliary body of rabbit eyes. The presence of ANF and its specific receptors in the ocular tissues suggests that this hormone might play a physiological role in the intraocular fluid homeostasis.     

Binding of ethidium to liver glutamate dehydrogenase.

Liver glutamate dehydrogenase forms a complex with ethidium bromide in solution; binding parameters of this complex depend on pH and enzyme concentration, but are independent of the ionic strength of solution. Binding of ethidium bromide occurs outside the coenzyme binding site, but appears to be closely related to the oligomer association sites of the enzyme.     

The politics of immigration locally: alliances between political parties and immigrant organizations

Alliances are a political opportunity that reinforce the claims made by different players in the political sphere. However, the literature on the political participation of immigrants pays little attention to the formation of alliances and their effects on the interaction between immigrants and institutional actors, especially under circumstances of politicization. This article aims to explain the emergence of alliances between political parties and immigrant organizations when immigration is politicized locally. I argue that the need to legitimize the political parties’ position on the politicization guide their alliances with immigrants. Using qualitative methods, I analyse the emergence of alliances in the anti-Romanian-Roma campaign in Badalona and the burka ban in Lleida, both in Catalonia, Spain. The findings portray these relationships as the outcome of strategic interactions that respond to the balance of power between institutional and non-institutional actors.     

Applying a framework for landscape planning under climate change for the conservation of biodiversity in the Finnish boreal forest

Conservation strategies are often established without consideration of the impact of climate change. However, this impact is expected to threaten species and ecosystem persistence and to have dramatic effects towards the end of the 21st century. Landscape suitability for species under climate change is determined by several interacting factors including dispersal and human land use. Designing effective conservation strategies at regional scales to improve landscape suitability requires measuring the vulnerabilities of specific regions to climate change and determining their conservation capacities. Although methods for defining vulnerability categories are available, methods for doing this in a systematic, cost‐effective way have not been identified. Here, we use an ecosystem model to define the potential resilience of the Finnish forest landscape by relating its current conservation capacity to its vulnerability to climate change. In applying this framework, we take into account the responses to climate change of a broad range of red‐listed species with different niche requirements. This framework allowed us to identify four categories in which representation in the landscape varies among three IPCC emission scenarios (B1, low; A1B, intermediate; A2, high emissions): (i) susceptible (B1 = 24.7%, A1B = 26.4%, A2 = 26.2%), the most intact forest landscapes vulnerable to climate change, requiring management for heterogeneity and resilience; (ii) resilient (B1 = 2.2%, A1B = 0.5%, A2 = 0.6%), intact areas with low vulnerability that represent potential climate refugia and require conservation capacity maintenance; (iii) resistant (B1 = 6.7%, A1B = 0.8%, A2 = 1.1%), landscapes with low current conservation capacity and low vulnerability that are suitable for restoration projects; (iv) sensitive (B1 = 66.4%, A1B = 72.3%, A2 = 72.0%), low conservation capacity landscapes that are vulnerable and for which alternative conservation measures are required depending on the intensity of climate change. Our results indicate that the Finnish landscape is likely to be dominated by a very high proportion of sensitive and susceptible forest patches, thereby increasing uncertainty for landscape managers in the choice of conservation strategies.     

Quantitative global studies of reactomes and metabolomes using a vectorial representation of reactions and chemical compounds

Background  

Global studies of the protein repertories of organisms are providing important information on the characteristics of the protein space. Many of these studies entail classification of the protein repertory on the basis of structure and/or sequence similarities. The situation is different for metabolism. Because there is no good way of measuring similarities between chemical reactions, there is a barrier to the development of global classifications of "metabolic space" and subsequent studies comparable to those done for protein sequences and structures.     

A novel substrate for yeast alcohol dehydrogenase – p-nitroso-N,N-dimethylaniline

Yeast alcohol dehydrogenase (EC 1.1.1.1) catalyzes the novel reduction of p-nitro-so-N,N-dimethylaniline with NADH as a cofactor. Apparent kinetic constants for this enzymatic reaction are: V ₂=2.1 s^–1, K _Q=456 M, K _iQ=119 M, and K _P=1.47 mM, at pH 8.9, 25 °C. This reaction is especially useful for the quantitative determination of NAD⁺ and NADH by enzymatic cycling.     

Influence of isoproterenol on net potassium uptake in whole pigeon erythrocytes in vitro

Isoproterenol increases net uptake of potassium in whole pigeon erythrocytes $\text{in vitro}$; effect of 10^?5 M isoproterenol is blocked by 10^?4 M propranolol. Pentifylline, a potent inhibitor of cAMP-phosphodiesterase, significantly amplifies effect of isoproterenol, indicating that isoproterenol-effect is mediated by cAMP. cAMP alone has no direct influence on net potassium uptake, while dibuturyl-cAMP has a very weak effect. Isoproterenol-effects are also mediated by the cell membrane protein-phosphorylation.     

State and accessibility of zinic in yeast alcohol dehydrogenase.

1. Yeast alcohol dehydrogenase (EC 1.1.1.1) is inhibited in the presence of 1,10-phenanthroline. 2. A conformational change in the enzyme's structure is induced by 1,10-phenanthroline, and is abolished in the presence of NADH. 1,10-Phenanthroline binds to the enzyme competitively with respect to NADH, with a stoicheiometry of 2 mol of 1,10-phenanthroline/144000g of enzyme. 3. 1,10-Phenanthroline induces a time-dependent dissociation of Zn2+ from the enzyme, which is in correlation with its inhibitions. 4. Spectrophotometric measurement indicates that the dissociation of half (2 zinc atoms/tetramer) of the total zinc content of the enzyme correlates with the full inhibition of its activity. Measurement of the tightly bound Zn2+ by atomic absorption photometry confirms this. 5. A proposition is advanced that the tetrameric molecule of yeast alcohol dehydrogenase possesses an inherent asymmetry, with four monomeric subunits being arranged in two mutually symmetrical pairs.