Hypercalcemia secondary to persistent hyperparathyroidism in kidney transplant patients: analysis after a year with cinacalcet.

Introduction: The most common cause of hypercalcemia in patients with transplanted kidneys is persistent hyperparathyroidism, which presents in 10%-30% of patients with functioning renal grafts. In these patients, the treatment of vitamin D-resistant hyperparathyroidism traditionally required parathyroidectomy. Calcimimetic agents represent a new therapeutic alternative; they inhibit parathyroid hormone (PTH) secretion, increasing the sensitivity of the calcium-sensitive receptor in the parathyroid gland.

Recombinant human follicular stimulating hormone and recombinant human luteinizing hormone in a 2:1 ratio combination. Pharmacological characteristics and clinical applications.

Importance Of The Field: A new fixed combination of recombinant human follicle stimulating hormone (r-hFSH) and recombinant human luteinizing hormone (r-hLH) at a 2:1 ratio has been recently developed to induce ovulation in patients with hypogonadotrophic hypogonadism. Whether or not this compound is useful for controlled ovarian stimulation for in vitro fertilization is still a matter of debate.

Areas Covered In This Review: Description of pharmacological and clinical aspects of this new product, through the analysis of the Phase I, II and II trials and post-marketing clinical randomized trials, performed since the initial assays in 1998 to nowadays.

The use of prediction models of spontaneous pregnancy in in vitro fertilization units reveals differences between the expected results of public and private clinics in Spain.

To evaluate the applicability of prediction models (PM) of spontaneous pregnancy (SP) in a population of infertile patients from a university-affiliated private assisted reproductive technology center (Instituto Valenciano de Infertilidad) and in the reproductive medicine section of a public university hospital (La Fe), both belonging to the same city (Valencia, Spain) between January and December 2008. We calculated the probability of SP using the PM developed by Hunault et al. in our two populations, and observed an estimated probability of SP<40% or the PM applicable in approximately 97% of the studied couples, and statistical differences between pregnancy probabilities in the two settings that were mainly a result of different age, sperm quality, and referral policies, leading us to conclude that the usefulness of PMs is limited in our environment.

Determination of the hydrophobicity of organic compounds measured as logP(o/w) through a new chromatographic method.

A new chromatographic method to determine the octanol-water partition coefficient (logP(o/w)) of organic substances is proposed in this paper. This method is based on a previously reported model that relates the retention factor in reversed-phase liquid chromatography with solute (p), mobile phase (P(m)(N)) and stationary phase (P(s)(N)) polarity parameters: logk=(logk)(0)+p(P(m)(N)-P(s)(N)). P(m)(N) values are calculated through expressions that depend only on the organic solvent fraction in the mobile phase.

Superficial siderosis mimicking amyotrophic lateral sclerosis.

We report a case of superficial siderosis erroneously diagnosed as amyotrophic lateral sclerosis. The patient's symptoms began 18 years prior with unilateral upper extremity weakness, fasciculations, and hyperreflexia. The patient then developed ataxia and hearing loss 15 years after his original symptoms.

A fast method for pKa determination by capillary electrophoresis.

In this article, we describe a recently developed capillary-electrophoresis method for the determination of acidity constants and compare it with other existing methods. The new method is based on the use of an internal standard (compound similar in nature and pKa value to the analyte), and offers several benefits, since it has all the advantages of capillary electrophoresis. In addition, it is very fast, because the exact measure of the pH of the separation electrolytes is not needed, and only a few electrophoretic runs are required to perform a pKa determination.

Kinetic and thermodynamic solubility values of some bioactive compounds.

Thermodynamic solubility is a decisive physicochemical property in drug development. The Chasing Equilibrium method offers an alternative to the classical procedures to measure the solubility of compounds with acid-base properties. The method is fast and yields accurate results.

Modeling the retention of neutral compounds in gradient elution RP-HPLC by means of polarity parameter models.

A three-parameter expression, which was already employed before for the prediction of the retention time in gradient mode in reversed-phase high-performance liquid chromatography (RP-HPLC) with satisfactory results, has been tested here under a variety of gradient patterns, using methanol and acetonitrile as the organic modifiers. A wide variety of compounds have been employed as test solutes, including some complex ones used as drugs, such as hydrocortisone and estriol. Simplifications of this expression have been made by considering two- and one-parameter expressions based on the p polarity parameter model, which was successfully employed before in isocratic mode to perform predictions of retention time.

Chromatographic hydrophobicity index: pH profile for polyprotic compounds.

The Chromatographic Hydrophobicity Index (CHI) has been measured for several diprotic compounds. In order to model the variation of CHI with pH, a general equation for polyprotic compounds which allows the calculation of CHI for each one of the species has been proposed. Different types of diprotic solutes have been selected: neutral acids, neutral bases, and amphiprotic compounds (non-zwitterionic and zwitterionic).

Decay of linkage disequilibrium within genes across HGDP-CEPH human samples: most population isolates do not show increased LD.

Background: It is well known that the pattern of linkage disequilibrium varies between human populations, with remarkable geographical stratification. Indirect association studies routinely exploit linkage disequilibrium around genes, particularly in isolated populations where it is assumed to be higher. Here, we explore both the amount and the decay of linkage disequilibrium with physical distance along 211 gene regions, most of them related to complex diseases, across 39 HGDP-CEPH population samples, focusing particularly on the populations defined as isolates.

Interrogating 11 fast-evolving genes for signatures of recent positive selection in worldwide human populations.

Different signatures of natural selection persist over varying time scales in our genome, revealing possible episodes of adaptative evolution during human history. Here, we identify genes showing signatures of ancestral positive selection in the human lineage and investigate whether some of those genes have been evolving adaptatively in extant human populations. Specifically, we compared more than 11,000 human genes with their orthologs in chimpanzee, mouse, rat, and dog and applied a branch-site likelihood method to test for positive selection on the human lineage.

Longitudinal study of intraneural perineurioma--a benign, focal hypertrophic neuropathy of youth.

The natural history of intraneural perineurioma has been inadequately studied. The aim of this study was to characterize the clinical presentation, electrophysiologic and imaging features and outcome of intraneural perineurioma. We ask if intraneural perineurioma is a pure motor syndrome that remains confined to one nerve and should be treated by surgical resection.

Retention of ionisable compounds on high-performance liquid chromatography XIX. pH variation in mobile phases containing formic acid, piperazine and tris as buffering systems and methanol as organic modifier.

In previous works a model to estimate the pH of methanol-aqueous buffer mobile phases from the aqueous pH and concentration of the buffer and the fraction of organic modifier was developed. This model was successfully applied and validated for buffers prepared from ammonia, acetic, phosphoric and citric acids. In the present communication this model has been extended to formic acid, piperazine and tris(hydroxymethyl)aminomethane buffers.

GnRH agonist administration at the time of implantation does not improve pregnancy outcome in intrauterine insemination cycles: a randomized controlled trial.

Objective: To assess whether GnRH agonist administration in the luteal phase improves pregnancy outcome in intrauterine insemination (IUI) cycles.

Design: Single-center, randomized, single-blind, placebo-controlled trial.

Setting: University-affiliated infertility clinic, between February 2005 and December 2007.

Prediction of retention in reversed-phase liquid chromatography by means of the polarity parameter model.

The polarity parameter model previously developed: log k=(log k)(0) + p(P(m)(N) - P(s)(N)) has been successfully applied to study several chromatographic systems involving new generation RPLC columns (Luna C18, Resolve C18, XTerra MSC18, and XTerra RP18). In this model the retention of the solutes (log k) is related to a solute parameter (p), a mobile phase parameter (P(m)(N)) and two chromatographic system parameters [P(s)(N) and (log k)(0)]. The studied systems have been characterized with different acetonitrile-water and methanol-water mobile phases, using a set of 12 neutral solutes of different chemical nature.

Low exchangeability of selenocysteine, the 21st amino acid, in vertebrate proteins.

Selenocysteine (Sec), the 21st amino acid, is incorporated into proteins through the recoding of a termination codon, an inefficient translational process mediated by a complex molecular machinery. Sec is a rare amino acid in extant proteins, chemically similar to cysteine (Cys), found in homologous position to Cys of nonselenoprotein families. Selenoproteins account for the dependence of vertebrates on environmental selenium (Se) and have an important role in several Se-deficiency diseases.

The relationship between the antimicrobial effect of catheter coatings containing silver nanoparticles and the coagulation of contacting blood.

It is well known that surface coatings for medical devices can be made antimicrobial through introduction of silver nanoparticles. By virtue of their extremely large surface-to-volume ratio, the silver particles serve as a depot for sustained release of silver ions, despite the fact that silver is not readily oxidized. Antimicrobial coatings are especially important in connection with indwelling catheters with a high risk of bacterial line infections, such as central venous catheters (CVCs).

Genetic and demographic implications of the Bantu expansion: insights from human paternal lineages.

The expansion of Bantu languages, which started around 5,000 years before present in west/central Africa and spread all throughout sub-Saharan Africa, may represent one of the major and most rapid demographic movements in the history of the human species. Although the genetic footprints of this expansion have been unmasked through the analyses of the maternally inherited mitochondrial DNA lineages, information on the genetic impact of this massive movement and on the genetic composition of pre-Bantu populations is still scarce. Here, we analyze an extensive collection of Y-chromosome markers--41 single nucleotide polymorphisms and 18 short tandem repeats--in 883 individuals from 22 Bantu-speaking agriculturalist populations and 3 Pygmy hunter-gatherer populations from Gabon and Cameroon.

Enthalpies and constants of dissociation of several neutral and cationic acids in aqueous and methanol/water solutions at various temperatures.

The acidic dissociation enthalpies and constants of anilinium, protonated tris(hydroxymethyl)aminomethane (HTris(+)), benzoic and acetic acids, have been determined at several temperatures in pure water and in methanol/water mixtures by potentiometry and by isothermal titration microcalorimetry (ITC). The pK(a) values determined by both techniques are in accordance when the dissociation process involves large amounts of heat. However, for the neutral acids the ITC technique gave slightly lower pK(a) values than those from potentiometry at the highest temperatures studied due to the small amounts of heat involved in the acidic dissociation.

Retention of ionisable compounds on high-performance liquid chromatography XVIII: pH variation in mobile phases containing formic acid, piperazine, tris, boric acid or carbonate as buffering systems and acetonitrile as organic modifier.

In the present work dissociation constants of commonly used buffering species, formic acid, piperazine, tris(hydroxymethyl)-aminomethane, boric acid and carbonate, have been determined for several acetonitrile-water mixtures. From these pK(a) values a previous model has been successfully evaluated to estimate pH values in acetonitrile-aqueous buffer mobile phases from the aqueous pH and concentration of the above mentioned buffers up to 60% of acetonitrile, and aqueous buffer concentrations between 0.005 (0.

Fast high-throughput method for the determination of acidity constants by capillary electrophoresis: I. Monoprotic weak acids and bases.

A new and fast method to determine acidity constants of monoprotic weak acids and bases by capillary zone electrophoresis based on the use of an internal standard (compound of similar nature and acidity constant as the analyte) has been developed. This method requires only two electrophoretic runs for the determination of an acidity constant: a first one at a pH where both analyte and internal standard are totally ionized, and a second one at another pH where both are partially ionized. Furthermore, the method is not pH dependent, so an accurate measure of the pH of the buffer solutions is not needed.

Retention models for ionizable compounds in reversed-phase liquid chromatography: effect of variation of mobile phase composition and temperature.

General models in reversed-phase liquid chromatography that have been extended to relate retention of ionizable compounds to mobile phase composition, pH and/or temperature are reviewed. In particular, the fundamentals and applications of the solvation parameter model, the polarity parameter model and several classical models based on empirical equations are presented and compared. A main parameter in all these models is the degree of ionization of the acid-base compound, which depends on both the pH of the mobile phase and the acid-base constant of the compound.

The genetic legacy of religious diversity and intolerance: paternal lineages of Christians, Jews, and Muslims in the Iberian Peninsula.

Most studies of European genetic diversity have focused on large-scale variation and interpretations based on events in prehistory, but migrations and invasions in historical times could also have had profound effects on the genetic landscape. The Iberian Peninsula provides a suitable region for examination of the demographic impact of such recent events, because its complex recent history has involved the long-term residence of two very different populations with distinct geographical origins and their own particular cultural and religious characteristics-North African Muslims and Sephardic Jews. To address this issue, we analyzed Y chromosome haplotypes, which provide the necessary phylogeographic resolution, in 1140 males from the Iberian Peninsula and Balearic Islands.