Triple Structural Transition below Room Temperature in the Antifilarial Drug Diethylcarbamazine Citrate

A very unusual triple structural transition pattern below room temperature was observed for the antifilarial drug diethylcarbamazine citrate. Besides the first thermal, crystallographic, and vibrational investigations of this first-line drug used in clinical treatment for lymphatic filariasis, a noteworthy behavior with three structural transformations as a function of temperature was demonstrated by differential scanning calorimetry, Raman spectroscopy, and single-crystal X-ray diffractometry. Our X-ray data on single crystals allow for a complete featuring and understanding of all transitions, since the four structures associated with the three solid-solid phase transformations were accurately determined. Two of three structural transitions show an order-disorder mechanism and temperature hysteresis with exothermic peaks at 224 K (T(1)`) and 213 K (T(2)`) upon cooling and endothermic ones at 248 K (T(1)) and 226 K (T(2)) upon heating. The other transition occurs at 108 K (T(3)) and it is temperature-rate sensitive. Molecular displacements onto the (010) plane and conformational changes of the diethylcarbamazine backbone as a consequence of the C-H center dot center dot center dot N hydrogen bonding formation/cleavage between drug molecules explain the mechanism of the transitions at T(1)`/T(2). However, such changes are observed only on alternate columns of the drug intercalated by citrate chains, which leads to a doubling of the lattice period along the a axis of the 235 K structure with respect to the 150 and 293 K structures. At T(2)`/T(1), these structural alterations occur in all columns of the drug. At T(3), there is a rotation on the axis of the N-C bond between the carbamoyl moiety and an ethyl group of one crystallographically independent diethylcarbamazine molecule besides molecular shifts and other conformational alterations. The impact of this study is based on the fascinating finding in which the versatile capability of structural adaptation dependent on the thermal history was observed for a relatively simple organic salt, diethylcarbamazine citrate.

Solvothermal Preparation of Drug Crystals: Didanosine

For the first time, crystals of suitable size for X-ray diffractometry structure determination (Dian important anti-HI V drug were prepared under solvothermal conditions. In this study, the crystal structure of didanosine (2`,3`-dideoxyinosine, ddI) in the form of a hydrate was determined using single-crystal X-ray diffractometry. Powder X-ray diffraction analysis revealed that the solid-state phase of the drug incorporated into pharmaceutical solid dosage forms is isostructural to the solvothermally prepared ddI material, even though they do not exhibit an identical chemical composition due to different water fractions occupying hydrophobic channels formed within the crystal lattice. Two ddI conformers are present in the structure, in agreement with a previous structure elucidation attempt. Concerning the keto enol equilibrium of ddI, our crystal data and vibrational characterizations by Fourier transform infrared (FTIR) and FT-Raman spectroscopy techniques were conclusive to state that both conformers exist in the keto form, contrary to solid-state NMR spectroscopic assignments that suggested ddI molecules occur as enol tautomers. In addition, characterizations by thermal (differential scanning calorimetry) and spectroscopic techniques allowed us to understand the structural similarities and the differences related to the hydration pattern of the nonstoichiometric hydrates.

Evaluation of dental pulp repair using low level laser therapy (688 nm and 785 nm) morphologic study in capuchin monkeys

The aim of this study was to evaluate the hypothesis that low-level laser therapy (LLLT) 688 nm and 785 nm accelerate dentin barrier formation and repair process after traumatic pulp exposure. The sample consisted of 45 premolars of capuchin monkeys (Cebus apella) with pulp exposure Class V cavities. All premolars were treated with calcium hydroxide (Ca(OH)(2)), divided in groups of 15 teeth each, and analyzed on 7(th), 25(th), and 60(th) day. Group GI - only Ca(OH)(2), GIF- laser 688 nm, and GIII - laser 785 nm. Laser beam was used in single and punctual dose with the parameters: continuous, 688 nm and 785 nm wavelength, tip`s area of 0.00785 cm(2), power 50 mW, application time 20 s, dose 255 J/cm(2), energy 2 J. Teeth were capped with Ca(OH)(2), Ca(OH)(2) cement and restored with amalgam. All groups presented pulp repair. On 25(th) day the thickness of the formed dentin barrier was different between the groups GI and GII (p < 0.05) and between groups GI and GIII (p < 0.01). On 60(th) day there was difference between GI and GIII (p < 0.01). It may be concluded that, LLLT 688 nm and 785 nm accelerated dentin barrier formation and consequently pulp repair process, with best results using infrared laser 785 nm. (c) 2009 by Astro Ltd. Published exclusively by WLLEY-VCH Verlag GmbH & Co. KGaA

Effect of low-level laser irradiation on odontoblast-like cells

Low-level laser therapy (LLLT), also referred to as therapeutic laser, has been recommended for a wide array of clinical procedures, among which the treatment of dentinal hypersensitivity. However, the mechanism that guides this process remains unknown. Therefore, the objective of this study was to evaluate in vitro the effects of LLL irradiation on cell metabolism (MTT assay), alkaline phosphatase (ALP) expression and total protein synthesis. The expression of genes that encode for collagen type-1 (Col-1) and fibronectin (FN) was analyzed by RT-PCR. For such purposes, oclontoblast-like cell line (MDPC-23) was previously cultured in Petri dishes (15000 cells/cm(2)) and submitted to stress conditions during 12 h. Thereafter, 6 applications with a monochromatic near infrared radiation (GaAlAs) set at predetermined parameters were performed at 12-h intervals. Non-irradiated cells served as a control group. Neither the MTT values nor the total protein levels of the irradiated group differed significantly from those of the control group (Mann-Whitney test; p > 0.05). On the other hand, the irradiated cells showed a decrease in ALP activity (Mann-Whitney test; p < 0.05). RT-PCR results demonstrated a trend to a specific reduction in gene expression after cell irradiation, though not significant statistically (Mann-Whitney test; p > 0.05). It may be concluded that, under the tested conditions, the LLLT parameters used in the present study did not influence cell metabolism, but reduced slightly the expression of some specific proteins.

An R implementation for generalized Birnbaum-Saunders distributions

The Birnbaum-Saunders (BS) model is a positively skewed statistical distribution that has received great attention in recent decades. A generalized version of this model was derived based on symmetrical distributions in the real line named the generalized BS (GBS) distribution. The R package named gbs was developed to analyze data from GBS models. This package contains probabilistic and reliability indicators and random number generators from GBS distributions. Parameter estimates for censored and uncensored data can also be obtained by means of likelihood methods from the gbs package. Goodness-of-fit and diagnostic methods were also implemented in this package in order to check the suitability of the GBS models. in this article, the capabilities and features of the gbs package are illustrated by using simulated and real data sets. Shape and reliability analyses for GBS models are presented. A simulation study for evaluating the quality and sensitivity of the estimation method developed in the package is provided and discussed. (C) 2008 Elsevier B.V. All rights reserved.

A two-component system, an anti-sigma factor and two paralogous ECF sigma factors are involved in the control of general stress response in Caulobacter crescentus

The extracytoplasmic function sigma factor sigma(T) is the master regulator of general stress response in Caulobacter crescentus and controls the expression of its paralogue sigma(U). In this work we showed that PhyR and NepR act, respectively, as positive and negative regulators of sigma(T) expression and function. Biochemical data also demonstrated that NepR directly binds sigma(T) and the phosphorylated form of PhyR. We also described the essential role of the histidine kinase gene CC3474, here denominated phyK, for expression of sigma(T)-dependent genes and for resistance to stress conditions. Additionally, in vivo evidence of PhyK-dependent phosphorylation of PhyR is presented. This study also identified a conserved cysteine residue (C95) located in the periplasmic portion of PhyK that is crucial for the function of the protein. Furthermore, we showed that PhyK, PhyR and sigma(T) regulate the same set of genes and that sigma(T) apparently directly controls most of its regulon. In contrast, sigma(U) seems to have a very modest contribution to the expression of a subset of sigma(T)-dependent genes. In conclusion, this report describes the molecular mechanism involved in the control of general stress response in C. crescentus.

Microbiopsies of Surface Dental Enamel as a Tool to Measure Body Lead Burden

Lead (Pb) poisoning is preventable but continues to be a public health problem in several countries. Measuring Pb in the surface dental enamel (SDE) using microbiopsies is a rapid, safe, and painless procedure. There are different protocols to perform these microbiopsies, but the reliability of dental enamel lead levels (DELL) determination is dependent upon biopsy depth (BD). It is established that DELL decrease from the outermost superficial layer to the inner layer of dental enamel. The aim of this study was to determine DELL obtained by two different microbiopsy techniques on SDE termed protocol I and protocol II. Two consecutive enamel layers were removed from the same subject group (n = 138) for both protocols. Protocol I consisted of a biopsied site with a diameter of 4 mm after the application of 10 l HCl for 35 s. Protocol II involved a biopsied site of 1.6 mm diameter after application of 5 l HCl for 20 s. The results demonstrated that there were no significant differences for BD and DELL between homologous teeth using protocol I. However, there was a significant difference between DELL in the first and second layers using both protocols. Further, the BD in protocol II overestimated DELL values. In conclusion, SDE analyzed by microbiopsy is a reliable biomarker in protocol I, but the chemical method to calculate BD in protocol II appeared to be inadequate for measurement of DELL. Thus, DELL could not be compared among studies that used different methodologies for SDE microbiopsies.

Antimicrobial Activity of Ethylenediaminedisuccinate Metal Complexes

It is shown that metal complexes of the biodegradable ligand ethylenediaminedisuccinic acid (edds) present antimicrobial activity towards fungi and bacteria. [Cd(edds)], in particular, is more toxic than free Cd2+ to Aspergillus niger, behaving as a `Trojan Horse` in the facilitated delivery of the toxic metal into the fungus.

The importance of protoporphyrin IX efflux for ALA-PDT dosimetry

One of the major advances in PDT is the use of 5-aminolevulinic acid (ALA) to induce the production of an enclogenous photosensitizer inside the cells using intracellular enzymatic pathways. ALA is the first intermediate in heme biosynthesis and a precursor of the protoporphyrin IX (PpIX). When activated by light, this efficient photosensitizer accumulated in the target cells can produce cytotoxicity. The aim of this study was to find the best conditions for cell killing using ALA to temporarily increase the concentration of PpIX in two cell lines. It was shown that a considerable efflux of synthesized PpIX occurs. Since this efflux is time-dependent, it is essential to know the optimum time for irradiation after ALA administration. So, the efflux of PpIX from the cells is an important parameter to be considered for ALA-PDT dosimetry.