Moderate sodium restriction with angiotensin converting enzyme inhibitor in essential hypertension: a double blind study.

Fifteen unselected patients who had essential hypertension and whose average supine blood pressure when they were not receiving any treatment and their usual sodium intake was 162/107 mm Hg were treated with captopril 50 mg twice daily. After one month''s treatment their supine blood pressure had decreased to 149/94 mm Hg. They were then instructed to reduce their sodium intake to about 80 mmol(mEq)/day. After two weeks of moderate sodium restriction they were entered into a double blind randomised crossover study comparing the effect of 10 Slow Sodium tablets (100 mmol sodium chloride) with matching placebo tablets while continuing to take captopril and restrict sodium in their diet. After one month of taking placebo their mean supine blood pressure was 137/88 mm Hg with a urinary sodium excretion of 83 mmol/24 h, while after one month of taking Slow Sodium tablets their mean supine blood pressure was 150/97 mm Hg (p less than 0.001) with a sodium excretion of 183 mmol/24 h. The mean supine blood pressure during moderate sodium restriction therefore decreased by 9% and correlated significantly with the reduction in urinary sodium excretion. These results suggest that the combination of treatment with a moderate but practical reduction in sodium intake and an angiotensin converting enzyme inhibitor is effective in decreasing the blood pressure in patients with essential hypertension. This combined approach overcomes some of the objections that have been made to salt restriction alone and to converting enzyme inhibitors alone.     

Lack of effect of oral magnesium on high blood pressure: a double blind study.

Seventeen unselected patients with mild to moderate essential hypertension and whose average supine blood pressure after two months'' observation with no treatment was 154/100 mm Hg were entered into a double blind randomised crossover study of one month''s treatment with magnesium aspartate (15 mmol magnesium/day) and treatment with placebo for a further month. This preparation of magnesium was well tolerated and did not cause diarrhoea. Despite a significant increase in plasma magnesium concentration and a significant increase in urinary excretion of magnesium while taking magnesium aspartate there was no fall in blood pressure compared with either treatment with placebo or values before treatment. The results provide no evidence for a role of dietary magnesium in the regulation of high blood pressure and are contrary to recent speculations.     

Involvement of Microorganisms in the Formation of Carbonate Speleothems in the Cervo Cave (L'Aquila-Italy)

Much is known about the bacterial precipitation of carbonate rocks, but comparatively little is known about the involvement of microbes in the formation of secondary mineral structures in caves. We hypothesized that bacteria isolated from calcareous stalactites, which are able to mediate CaCO₃ precipitation in vitro, play a role in the formation of carbonate speleothems. We collected numerous cultivable calcifying bacteria from calcareous speleothems from Cervo cave, implying that their presence was not occasional. The relative abundance of calcifying bacteria among total cultivable microflora was found to be related to the calcifying activity in the stalactites. We also determined the δ ¹³C and δ ¹⁸ O values of the Cervo cave speleothems from which bacteria were isolated and of the carbonates obtained in vitro to determine whether bacteria were indeed involved in the formation of secondary mineral structures. We identified three groups of biological carbonates produced in vitro at 11°C on the basis of their carbon isotopic composition: carbonates with δ ¹³C values (a) slightly more positive, (b) more negative, and (c) much more negative than those of the stalactite carbonates. The carbonates belonging to the first group, characterized by the most similar δ ¹³C values to stalactites, were produced by the most abundant strains. Most of calcifying isolates belonged to the genus Kocuria. Scanning electron microscopy showed that dominant morphologies of the bioliths were sherulithic with fibrous radiated interiors. We suggest a mechanism of carbonate crystal formation by bacteria.     

Determination of the optimal therapeutic protocols in cancer immunotherapy

Cancer immunotherapy aims at eliciting an immune system response against the tumor. However, it is often characterized by toxic side-effects. Limiting the tumor growth and, concurrently, avoiding the toxicity of a drug, is the problem of protocol design. We formulate this question as an optimization problem and derive an algorithm for its solution. Unlike the standard optimal control approach, the algorithm simulates impulse-like drug administrations. It relies on an exact computation of the gradient of the cost function with respect to any protocol by means of the variational equations, that can be solved in parallel with the system. In comparison with previous versions of this method [F. Castiglione, B. Piccoli, Optimal control in a model of dendritic cell transfection cancer immunotherapy, Bull. Math. Biol. 68 (2006) 255-274; B. Piccoli, F. Castiglione, Optimal vaccine scheduling in cancer immunotherapy, Physica A. 370 (2) (2007) 672-680], we optimize both the timing and the dosage of each administration and introduce a penalty term to avoid clustering of subsequent injections, a requirement consistent with the clinical practice. In addition, we implement the optimization scheme to simulate the case of multi-therapies. The procedure works for any ODE system describing the pharmacokinetics and pharmacodynamics of an arbitrary number of therapeutic agents. In this work, it was tested for a well known model of the tumor-immune system interaction [D. Kirschner, J.C. Panetta, Modeling immunotherapy of tumor-immune interaction, J. Math. Biol. 37 (1998) 235-252]. Exploring three immunotherapeutic scenarios (CTL therapy, IL-2 therapy and combined therapy), we display the stability and efficacy of the optimization method, obtaining protocols that are successful compromises between various clinical requirements.     

Characterization of single nucleotide polymorphisms in sheep and their variation as evidence of selection

The discovery of SNPs was performed using animals from eight European sheep breeds. Eleven SNPs were further characterized using about 1,700 sheep belonging to 57 breeds. A method for the identification of loci that were likely subject to selection was applied; three of the 11 SNPs lying outside the 95% confidence region of the conditional joint distribution of F(ST) and mean heterozygosity were identified as outliers.     

Quantifying size distributions of nanolipoprotein particles with single-particle analysis and molecular dynamic simulations

Self-assembly of purified apolipoproteins and phospholipids results in the formation of nanometer-sized lipoprotein complexes, referred to as nanolipoprotein particles (NLPs). These bilayer constructs are fully soluble in aqueous environments and hold great promise as a model system to aid in solubilizing membrane proteins. Size variability in the self-assembly process has been recognized for some time, yet limited studies have been conducted to examine this phenomenon. Understanding the source of this heterogeneity may lead to methods to mitigate heterogeneity or to control NLP size, which may be important for tailoring NLPs for specific membrane proteins. Here, we have used atomic force microscopy, ion mobility spectrometry, and transmission electron microscopy to quantify NLP size distributions on the single-particle scale, specifically focusing on assemblies with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and a recombinant apolipoprotein E variant containing the N-terminal 22 kDa fragment (E422k). Four discrete sizes of E422k/DMPC NLPs were identified by all three techniques, with diameters centered at approximately 14.5, 19, 23.5, and 28 nm. Computer simulations suggest that these sizes are related to the structure and number of E422k lipoproteins surrounding the NLPs and particles with an odd number of lipoproteins are consistent with the double-belt model, in which at least one lipoprotein adopts a hairpin structure.