Synthesis of some new 2-alpha-L-arabinopyranosyl-1,2,4-triazines as potential antitumor chemotherapeutics

Synthetic routes towards different 2-alpha-L-arabinopyranosyl-3-thioxo-2,3-dihydro-1,2,4-triazin-5(4H)-/ones or thiones were investigated. Primary human anticancer screening of two selected compounds resulted in an active compound against SF-268 (CNS) cell line.     

Characterisation of two novel types of hexactinomyxon spores (Myxozoa) with subsidiary protrusions on their caudal processes

Two types of hexactinomyxon spores, Hexactinomyxon type 1 nov. and Hexactinomyxon type 2 nov., are reported from freshwater tubificid oligochaetes, Limnodrilus hoffmeisteri and L. udekemianus. Spores are triradially symmetrical and comprise a spore body, style and 6 caudal processes. The caudal processes arise from the division of each of the 3 valve cells into an equal pair of projections at the base of the style. One of each pair is fused conspicuously to its nearest neighbour for the initial 1/5 to 1/4 of their total length. Distally, each process possesses subsidiary protrusions which are irregularly distributed and irregularly shaped extensions of the valve cell. Scanning electron microscopy of Hexactinomyxon type 2 nov. revealed that these protrusions are a seamless extension of the valve cell wall which branch distally, occasionally laterally, and terminate in a distinct bulbous structure; they also form the terminus of each process. The small subunit ribosomal DNA gene (18S) of both hexactinomyxon types was amplified through a nested PCR, then digested with the restriction enzymes Dde I and Hha I. The resultant cleavage patterns suggested the presence of 2 forms. Subsequent partial sequencing of 18S rDNA confirmed the identification of 2 novel types.     

Value of Dynamic Susceptibility Contrast Perfusion MRI in the Acute Phase of Transient Global Amnesia

Purpose

Transient global amnesia (TGA) is a transitory, short-lasting neurological disorder characterized by a sudden onset of antero- and retrograde amnesia. Perfusion abnormalities in TGA have been evaluated mainly by use of positron emission tomography (PET) or single-photon emission computed tomography (SPECT). In the present study we explore the value of dynamic susceptibility contrast perfusion-weighted MRI (PWI) in TGA in the acute phase.

Methods

From a MRI report database we identified TGA patients who underwent MRI including PWI in the acute phase and compared these to control subjects. Quantitative perfusion maps (cerebral blood flow (CBF) and volume (CBV)) were generated and analyzed by use of Signal Processing In NMR-Software (SPIN). CBF and CBV values in subcortical brain regions were assessed by use of VOI created in FIRST, a model-based segmentation tool in the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library (FSL).

Results

Five TGA patients were included (2 men, 3 women). On PWI, no relevant perfusion alterations were found by visual inspection in TGA patients. Group comparisons for possible differences between TGA patients and control subjects showed significant lower rCBF values bilaterally in the hippocampus, in the left thalamus and globus pallidus as well as bilaterally in the putamen and the left caudate nucleus. Correspondingly, significant lower rCBV values were observed bilaterally in the hippocampus and the putamen as well as in the left caudate nucleus. Group comparisons for possible side differences in rCBF and rCBV values in TGA patients revealed a significant lower rCBV value in the left caudate nucleus.

Conclusions

Mere visual inspection of PWI is not sufficient for the assessment of perfusion changes in TGA in the acute phase. Group comparisons with healthy control subjects might be useful to detect subtle perfusion changes on PWI in TGA patients. However, this should be confirmed in larger data sets and serial PWI examinations.     

The PKD Inhibitor CID755673 Enhances Cardiac Function in Diabetic db/db Mice

The development of diabetic cardiomyopathy is a key contributor to heart failure and mortality in obesity and type 2 diabetes (T2D). Current therapeutic interventions for T2D have limited impact on the development of diabetic cardiomyopathy. Clearly, new therapies are urgently needed. A potential therapeutic target is protein kinase D (PKD), which is activated by metabolic insults and implicated in the regulation of cardiac metabolism, contractility and hypertrophy. We therefore hypothesised that PKD inhibition would enhance cardiac function in T2D mice. We first validated the obese and T2D db/db mouse as a model of early stage diabetic cardiomyopathy, which was characterised by both diastolic and systolic dysfunction, without overt alterations in left ventricular morphology. These functional characteristics were also associated with increased PKD2 phosphorylation in the fed state and a gene expression signature characteristic of PKD activation. Acute administration of the PKD inhibitor CID755673 to normal mice reduced both PKD1 and 2 phosphorylation in a time and dose-dependent manner. Chronic CID755673 administration to T2D db/db mice for two weeks reduced expression of the gene expression signature of PKD activation, enhanced indices of both diastolic and systolic left ventricular function and was associated with reduced heart weight. These alterations in cardiac function were independent of changes in glucose homeostasis, insulin action and body composition. These findings suggest that PKD inhibition could be an effective strategy to enhance heart function in obese and diabetic patients and provide an impetus for further mechanistic investigations into the role of PKD in diabetic cardiomyopathy.     

Evaluation of the 2013 Southeast Asian Haze on Solar Generation Performance

Pollution in Southeast Asia is a major public energy problem and the cause of energy losses. A significant problem with respect to this type of pollution is that it decreases energy yield. In this study, two types of photovoltaic (PV) solar arrays were used to evaluate the effect of air pollution. The performance of two types of solar arrays were analysed in this research, namely, two units of a 1 kWp tracking flat photovoltaic (TFP) and two units of a 1 kWp fixed flat photovoltaic arrays (FFP). Data analysis was conducted on 2,190 samples at 30 min intervals from 01^st June 2013, when both arrays were washed, until 30^th June 2013. The performance was evaluated by using environmental data (irradiation, temperature, dust thickness, and air pollution index), power output, and energy yield. Multiple regression models were predicted in view of the environmental data and PV array output. Results showed that the fixed flat system was more affected by air pollution than the tracking flat plate. The contribution of this work is that it considers two types of photovoltaic arrays under the Southeast Asian pollution 2013.     

Molecular Expression of Some Oncogenes and Predisposing Behaviors Contributing to the Aggressiveness of Prostate Cancer

Background:Prostate cancer is the second most common cancer in men in Iran. It can be treated in the early stages of the disease; therefore, early diagnosis can be lifesaving. The aim of this study was to investigate the molecular expression of some oncogenes and predisposing behaviors contributing to the aggressiveness of prostate cancer.Methods:In this case-control study, prostate cancer specimens were collected from both patients and healthy volunteers. Several factors such as age, family history, smoking, and stage of the disease, were investigated based on the criteria of this study. Real-time PCR was used to measure the expression of four oncogenes. Statistical analysis of our data was carried out using SPSS software version 22.Results:The X² test showed that there was a difference in the incidence of prostate cancer in different age groups (X²= 9.30; p= 0.026). Although data analysis by the X² test showed that family history had a significant effect on prostate cancer (X²= 14.43; p= 0.001), smoking did not show a significant effect on the incidence of this disorder (X²= 4.67; p= 0.097). The T2N1M0 stage is the most common form of prostate cancer in patients with family history of prostate cancer and the habit of smoking. Also, the expression of KRAS1P, GLB1L2, SChLAP1 and PACSIN3 oncogenes reduced in prostate cancer samples compared to the control group.Conclusion:Overall, functional interpretation of gene expression in the prostate tissue can affect tumor progression. Yet, further practical studies are required to reveal the accurate underlying mechanisms.Key Words: Age, Family History, Oncogenes, Prostate Cancer, Smoking     

Proinflammatory cytokine gene polymorphisms in Behçet's disease

Beh?et's disease (BD) is a chronic, systemic disease, characterized by oral and genital lesions, and ocular inflammation. There is evidence indicating altered levels of proinflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) in patients with BD. This study involved 150 patients with BD and 140 healthy controls, and investigated the role of proinflammatory cytokine gene polymorphisms in the disease. The frequency of the TNF-α (-238) G/G genotype was significantly higher in the patient group, compared to the controls (p < 0.001), whilst the G/A genotype was significantly lower in the patients with BD (p < 0.001). Patients with BD showed a significant increase in the TNF-α (- 308, - 238) GG haplotype (p < 0.001), whilst there was a significant decrease in the GA haplotype (p < 0.001). The heterozygous, IL-6 (- 174) C/G genotype (p = 0.005), and the IL-6 (- 174, nt565) haplotype CG (p < 0.001), were significantly decreased in the patient group. The increased production of proinflammatory cytokines in BD could be a consequence of specific, cytokine gene polymorphisms. Particular genotypes and haplotypes in TNF-α were over-represented in BD, which may, in turn, predispose individuals to this disease.     

PKI-179: An orally efficacious dual phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor

A series of mono-morpholino 1,3,5-triazine derivatives (8a–8q) bearing a 3-oxa-8-azabicyclo[3.2.1]octane were prepared and evaluated for PI3-kinase/mTOR activity. Replacement of one of the bis-morpholines in lead compound 1 (PKI-587) with 3-oxa-8-azabicyclo[3.2.1]octane and reduction of the molecular weight yielded 8m (PKI-179), an orally efficacious dual PI3-kinase/mTOR inhibitor. The in vitro activity, in vivo efficacy, and PK properties of 8m are discussed.