TAP1 and TAP2 gene polymorphisms in childhood cystic echinococcosis

The incidence of cystic echinococcosis (CE) due to Echinococcus granulosus is as high as 2000–2500 patients per year in Turkey. Whether genetic characteristics of the Turkish population cause a tendency to the disease is currently unknown. We aimed at studying the role of TAP gene polymorphisms in Turkish children with cystic echinococcosis. For an overview of allelic distribution of TAP1 and TAP2 genes, genotypes of 85 patients with CE and 100 controls were studied. To determine the genotype–phenotype correlation, 81 of the patients whose clinical data were available were analyzed. For TAP1-637, Asp/Gly heterozygosity was significantly more prevalent in CE patients than in controls (20 vs. 4%, odds ratio 6.0), while Gly/Gly homozygosity was less frequent (5 vs. 14%). For TAP2-379, Ile/Val heterozygosity was significantly more prevalent in CE patients than in controls (14 vs. 1%, odds ratio 16.27), while Ile/Ile homozygosity was less frequent (13 vs. 25%). TAP1-637 and TAP2-379 polymorphisms may have a role in causing genetic tendency for CE in children. The data may reflect the genetic properties of the Turkish population or may reveal the minor role of TAP gene polymorphisms in CE.     

Identification of a potent and selective non-basic cathepsin K inhibitor

Based on our previous study with trifluoroethylamine as a P2-P3 amide isostere of cathepsin K inhibitor, further optimization led to identification of compound 22 (L-873724) as a potent and selective non-basic cathepsin K inhibitor. This compound showed excellent pharmacokinetics and efficacy in an ovariectomized (OVX) rhesus monkey model. The volumes of distribution close to unity were consistent with this compound not being lysosomotropic, which is a characteristic of basic cathepsin K inhibitors.     

Treatment of dye-rich wastewater by an immobilized thermophilic cyanobacterial strain: Phormidium sp.

The removal of Remazol Blue and Reactive Black B by the immobilized thermophilic cyanobacterial strain Phormidium sp. was investigated under thermophilic conditions in a batch system, in order to determine the optimal conditions required for the highest dye removal. In the experiments, performed at pH 8.5, with different initial dye concentrations between 9.1 mg l⁻¹ and 82.1 mg l⁻¹ and at 45 °C, calcium alginate immobilized Phormidium sp. showed high dye decolorization, with maximum uptake yields ranging from 50% to 88% at all dye concentrations tested. When the effects of high dye concentrations on dye removal were investigated, the highest uptake yield in the beads was 50.3% for 82.1 mg l⁻¹ Remazol Blue and 60.0% for 79.5 mg l⁻¹ Reactive Black B. The highest color removal was detected at 45 °C and 50 °C incubation temperatures for all dye concentrations. As the temperature decreased, the removal yield of immobilized Phormidium sp. also decreased. At about 75 mg l⁻¹ initial dye concentrations, the highest specific dye uptake measured was 41.29–41.17 mg g⁻¹ for Remazol Blue and 47.69–43.82 mg g⁻¹ for Reactive Black B at 45 °C and 50 °C incubation temperatures, respectively, after 8 days incubation.     

The vertebrate segmentation clock: the tip of the iceberg

The vertebrate segmentation clock was identified 10 years ago as a molecular oscillator associated with the rhythmic production of embryonic somites. Since then, three major signaling pathways--Notch, FGF, and Wnt--have been shown to be activated periodically during segmentation and proposed to constitute the clockwork of the system. However, recent results from zebrafish embryonic studies demonstrate that Notch signaling is involved in the coupling of oscillations among cells rather than in the pacemaker of the oscillator. Furthermore, genetic analyses in mouse indicate that Wnt and FGF play only a permissive role in the control of the oscillations. Therefore, the nature of the segmentation clock pacemaker still remains elusive.     

Epileptic seizures induce structural and functional alterations on brain tissue membranes

Epilepsy is characterized by disruption of balance between cerebral excitation and inhibition, leading to recurrent and unprovoked convulsions. Studies are still underway to understand mechanisms lying epileptic seizures with the aim of improving treatment strategies. In this context, the research on brain tissue membranes gains importance for generation of epileptic activities. In order to provide additional information for this field, we have investigated the effects of pentylenetetrazol-induced and audiogenetically susceptible epileptic seizures on structure, content and function of rat brain membrane components using Fourier transform infrared (FT-IR) spectroscopy.     

Molecular phylogenetic analysis of Tulipa (Liliaceae) based on noncoding plastid and nuclear DNA sequences with an emphasis on Turkey

We investigated the phylogenetic relationships in Tulipa in Turkey using DNA sequences from the plastid trnL‐trnF region and the internal transcribed spacer (ITS) of nuclear ribosomal DNA. We generated trnL‐trnF and nuclear ITS sequences for 11 Tulipa spp. from Turkey and compared the utility of trnL‐trnF and ITS sequences for phylogenetic analysis. Neighbor‐joining, Bayesian and maximum parsimony methods were implemented using the same matrices. Our study of Tulipa based on molecular data revealed congruent results with previous studies. Despite the relatively lower resolution of trnL‐trnF than that of ITS, both sequence matrices generated similar results. Three clades were clearly distinguished, corresponding to subgenera Tulipa, Eriostemones and Orithyia. It is not fully resolved whether Clusianae should be recognized as a separate section of subgenus Tulipa or a distinct subgenus. © 2013 The Linnean Society of London, Botanical Journal of the Linnean Society, 2013, 172 , 270–279.     

Biomolecular Structure and Composition Changes in the Root System of Long-Lipped Serapias (Serapias vomeracea) After In Vitro Chitosan and Plant Growth Regulator Treatments

In the current study, effects of chitosan oligomers (CHI-OM) with different polymerization degrees (DP) between 2 and 15, and polymeric chitosan (CHI-P) with a DP of 70 were compared with kinetin (KIN), 6-benzylaminopurine (BAP), indole-3-butyric acid (IBA), indole-3-acetic acid (IAA), and jasmonic acid (JAS) on the structure and composition of several biomolecules in the root system of Serapias vomeracea. Evaluation of molecular alterations in the root system of S. vomeracea through an infrared spectroscopic approach provided insight into the differentiation between action mechanisms of chitosan and commonly used plant growth regulators. The results revealed that CHI-P and JAS treatments at low concentrations might enhance the lignin content in the cell walls. Also, JAS, CHI-OM, and CHI-P treatments enhanced cell wall lignification. The water-associated cellulose content of the cell walls was affected by the DP of chitosan. Membrane lipid stabilization and protein content were enhanced after CHI-P, JAS, and KIN treatments, while BAP and CHI-OM treatments triggered lipid, protein, and cell wall polysaccharide synthesis. In particular, CHI-OM treatment also enhanced rhamnogalacturonan and β-galactan content as well as xyloglucans and glucomannans, while the auxin treatments had a similar impact only on glucomannan content. These findings suggest that chitosan may show either purine-based cytokinin-like or lipid-based jasmonic acid-like activity in the root system of S. vomeracea. Additionally, depending on its degree of polymerization, the effects of chitosan may vary on root system development in S. vomeracea.

     

The role of the PTEN/mTOR axis in clinical response of rectal cancer patients

Background

Preoperative chemoradiotherapy has long been accepted as a method to improve survival and lifetime quality of rectal cancer patients. However, physiologic effects of these therapies largely depend on the resistance of cells to the radiation, type of chemotherapeutic agents and individual responses. As one of the signaling cascades involved in chemo- or radiation- resistance, the present study focused on several proteins involved in pTEN/Akt/mTOR pathway to explore their prognostic significance.

Materials and methods

Samples from advanced stage rectal cancer patients were analyzed to detect expression levels of pTEN/Akt/mTOR pathway related proteins pTEN, mLST8, REDD1, BNIP3, SAG and NOXA, together with p53, by RT-qPCR. Kaplan–Meier analysis was used to assess expression-survival relation and correlations among all proteins and clinicopathological features were statistically analyzed.

Results.

Except p53, none of the proteins showed prognostic significance. High p53 expression presented clear impact on overall survival and disease free survival. It was also significantly related to pathologic complete response. p53 showed high correlation to local recurrence as well. On the other hand, strong correlation was observed with PTEN expression and tumor response, but not with survival. High associations were also observed between mLST8/REDD1, PTEN and NOXA, confirming their role in the same cascade.

Conclusion

The contentious role of p53 as a prognostic biomarker in colorectal cancer was further affirmed, while PTEN and REDD1 could be suggested as potential candidates. Additionally, NOXA emerges as a conjunctive element for different signaling pathways.

     

Biopolymer-Based Transdermal Films of Donepezil as an Alternative Delivery Approach in Alzheimer’s Disease Treatment

Matrix type transdermal films of donepezil (DNP) as an alternative delivery approach was designed to improve patient compliance to Alzheimer disease treatment. Sodium alginate, a natural polysaccharide, was used as matrix-forming agent in the optimization of transdermal films. Propylene glycol and dl-limonene was added into films as a plasticizer and permeation enhancer, respectively. As well as mechanical strength and bioadhesiveness of optimized transdermal films of DNP, the impact of dl-limonene concentration in films on DNP in vitro permeation across pig skin was assessed. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) measurements were carried out to examine the effects of enhancer on in vitro conformational order of the stratum corneum intercellular lipids following permeation study. Results showed that transdermal formulations of DNP were suitable due to both mechanical and bioadhesive features of the films. In vitro skin permeation study indicated that dl-limonene at a concentration of 3% was optimum with high drug flux. ATR-FTIR results confirmed a more fluidized stratum corneum lipid state in the presence of dl-limonene, indicating its permeation enhancement effect. Regarding to achieve therapeutic levels of DNP, it seems to be feasible deliver DNP with transdermal films for the management of Alzheimer disease.KEY WORDS: Alzheimer disease, donepezil, limonene, permeation enhancement, transdermal film     

Spectrofluorimetric determination of nomifensine in human plasma and urine by derivatization with fluorescamine

A sensitive, simple and rapid spectrofluorimetric method was developed for the determination of nomifensine in human plasma and urine. The present method was based on the derivatization by fluorescamine in phosphate buffer at pH 4.0 to produce a highly fluorescent product which was measured at 488 nm (excitation at 339 nm). The method was validated according to the ICH guidelines with respect to linearity, limit of detection, limit of quantification, accuracy, precision, recovery and robustness. The assay was linear over the concentration ranges 100–2,000 and 50–2,000 ng/mL for plasma and urine, respectively. The limits of detection were calculated to be 13.9 and 7.5 ng/mL for plasma and urine, respectively. The method was successfully applied to the analysis of the drug in human plasma and urine. Copyright © 2011 John Wiley & Sons, Ltd.