Inter-rater reliability of physiotherapists using the Action Research Arm Test in chronic stroke

Objectives:The purpose of this study is to establish whether physiotherapists’ ratings are consistent, when using the Action Research Arm Test (ARAT) to score a chronic stroke patient.Methods:This was part of a large project establishing the reliability in chronic stroke. This study used a correlational design comparing the association between physiotherapist scores of the same patient, to establish the ARAT’s inter-rater reliability. The COSMIN checklist was followed to enhance the methodology of the study.Results:Twenty physiotherapists (8 female and 12 male) aged between 25 and 53 years were selected. There were no participant dropouts or withdrawals. The sample size was normally distributed. The physiotherapists appeared representative of the UK physiotherapy population, with the exception of gender. The distribution of scores showed a normal distribution with standard deviation of score of 1.9. The Kendall’s W test showed 0.711 of agreement between the raters. The scores achieved statistical significance showing consistency between physiotherapists’ scores with chronic stroke. Limitations of the study were the use of a small single center convenience sample that may reduce the generalizability of the findings.Conclusions:The ARAT is consistent when scored by physiotherapists in a chronic stroke population. The inter-rater reliability range was (0.70 to 0.90) which is categorized as good.     

Influence of surface shape on DNA binding of bimetallo helicates

In order to probe the DNA-helicate interactions responsible for the DNA binding and remarkable changes of the DNA secondary structure induced by a tetracationic bi-metallo helicate [Fe(2)(L(1))(3)](4+) (L(1)=C(25)H(20)N(4)), we have designed and synthesised derivatives with hydrophobic methyl groups at different positions on the ligand backbone. Two dimetallo helicates [Fe(2)(L(i))(3)](4+) were prepared using ligands L(3) and L(5) with the methyl substituent on, respectively, the 3 and 5 positions of the pyridyl ring thus producing a wider or slightly longer tetracationic DNA binder. UV/visible absorbance, circular and linear dichroism spectroscopies have been used to characterize the interactions of the cylinders with DNA with the aim of investigating any sequence preference or selectivity upon binding. Competitive binding studies using fluorescent dyes Hoechst 33258 (a minor groove binder), ethidium bromide (an intercalator) and a major groove binding cation (cobalt (III) hexammine) which induces the B-->Z transition have been employed to determine the binding geometries of the enantiomers of two methylated helicates (L(3) and L(5)) to DNA and compare with the data obtained previously for the unmethylated analogue (L(1)). The results demonstrate that the racemic mixtures and the resolved enantiomers of all helicates bind to DNA inducing structural changes. The overall conclusion from the effect of adding these groups to the surface of the parent helicate is that increasing the width (L(3)) reduces the DNA binding strength, the bending and coiling effect and the groove selectivity of the enantiomers compared with the parent compound. There is limited evidence to suggest a slight GC sequence preference. Lengthening the helicate (L(5)) results in DNA interactions similar to those of the parent compounds, with an increased preference of the P enantiomer for the minor groove indicating an enhancement of mode selectivity.     

Variations in random amplified polymorphic DNA profile and toxin production among isolates of Colletotrichum falcatum Went from sugarcane in Tamil Nadu,India

Red rot, caused by Colletotrichum falcatum Went, is one of the most important diseases of sugarcane (Saccharum officinarum L.). The pathogen shows a great diversity in virulence as a number of pathotypes are known to occur in nature. In the present study, the toxin producing ability and genetic variability among isolates of C. falcatum collected from major sugarcane growing areas of Tamil Nadu, India were analysed. The C. falcatum isolates differed significantly in their ability to produce toxin in vitro. The toxin from C. falcatum isolate Cf 671a induced the maximum electrolyte leakage (300 μS) from sugarcane leaf tissues. The genetic relatedness of the isolates of C. falcatum differing in toxin production potential was investigated by using RAPD analysis. Analysis of the genetic coefficient matrix derived from the scores of RAPD profiles showed that minimum and maximum percent similarities among the tested C. falcatum isolates were in the range of 19 to 95% respectively. The phylogenetic analysis by the UPGMA identified two main clusters. Cluster A contains only one isolate (Cf 98061) and all the other isolates were placed in Cluster B confirming high genetic diversity among the isolates. No correlation was observed between clustering of the C. falcatum isolates in the dendrogram and their toxin producing abilities.     

Estimation of Jordanian isolated Pectobacterium cellulase,pectinase concentrations,RAPD polymorphism and their maceration activity

Forty-two Pectobacterium isolates were recovered from contaminated soil and rotted vegetables in Jordan. Twenty of them were belonged to; Pectobacterium carotovorum subsp. Carotovorum (Pbc) (= Erwinia carotovora subsp. carotovora), 11 isolates were belonged to Pectobacterium atrospeticum (= Erwinia carotovora subsp. atroseptica) (Pba) and 11 isolates were not classifiable (Pbs). Maceration activity of the 42 proved their ability to macerate potato, carrot and radish slices. Maceration activity of the isolates either of the same subspecies or in between the isolates of different subspecies isolated from the same host or from different hosts was varied. The measured concentration in μM?ml^?1 of both cellulase and pectinase enzymes was variable too. The Rapid amplified polymorphic DNA-PCR finger printing of total genomic DNA using a pair of 10-mer oligonucleotide primers amplification showed similar DNA bands with some polymorphic variations amongst the isolates.     

Evaluation of antitumor effects of VEGFR-2 inhibitor F16 in a colorectal xenograft model

Biotechnology Letters - Colorectal cancer (CRC) is the third most prevalent type of cancer in the United States. The treatment options for cancer include surgery, chemotherapy, radiation,...     

Reactive oxygen species upregulate expression of PAI-1 in endothelial cells

Second messengers involved in the signal transduction pathway leading to induction of the plasminogen activator inhibitor (PAI-1) have not yet been well characterized. This study focuses on the mechanisms of regulation of PAI-1 expression by reactive oxygen species (ROS) in human endothelial cells. Inhibition of the tumor necrosis factor alpha (TNFalpha?-induced expression of PAI-1 by antioxidant N-acetyl-L-cysteine (NAC) indicated redox-sensitive mechanisms involved in the signaling pathway. Because TNFalpha induces PAI-1 production in endothelial cells, and NAC attenuated this response, we attempted to investigate the possible involvement of ROS in the activation of PAI-1 by TNFalpha. Upregulation of PAI-1 expression in endothelial cells by the stimulation with TNFalpha (50 ng/ml) or H2O2 (10-200 micro M), observed by measurement of the antigen and mRNA levels, was reversed in the presence of NAC (20mM). The stimulatory effect of ROS was detected also at the level of the PAI-1 promoter in endothelial cells transfected with plasmid p800 LUC containing a PAI-1 promoter fragment (+71 to -800). The PAI-1 promoter activity was increased in the presence of ROS, and was suppressed by up to 75% in the presence of antioxidants. On the basis of this study we can conclude that reactive oxygen species play an important role in a cytokine-induced activation of PAI-1 expression, and may act as a signal transduction messenger.     

Autophagic dysfunction in Alzheimer’s disease: Cellular and molecular mechanistic approaches to halt Alzheimer’s pathogenesis

Autophagy is a preserved cytoplasmic self-degradation process and endorses recycling of intracellular constituents into bioenergetics for the controlling of cellular homeostasis. Functional autophagy process is essential in eliminating cytoplasmic waste components and helps in the recycling of some of its constituents. Studies have revealed that neurodegenerative disorders may be caused by mutations in autophagy-related genes and alterations of autophagic flux. Alzheimer’s disease (AD) is an irrevocable deleterious neurodegenerative disorder characterized by the formation of senile plaques and neurofibrillary tangles (NFTs) in the hippocampus and cortex. In the central nervous system of healthy people, there is no accretion of amyloid β (Aβ) peptides due to the balance between generation and degradation of Aβ. However, for AD patients, the generation of Aβ peptides is higher than lysis that causes accretion of Aβ. Likewise, the maturation of autophagolysosomes and inhibition of their retrograde transport creates favorable conditions for Aβ accumulation. Furthermore, increasing mammalian target of rapamycin (mTOR) signaling raises tau levels as well as phosphorylation. Alteration of mTOR activity occurs in the early stage of AD. In addition, copious evidence links autophagic/lysosomal dysfunction in AD. Compromised mitophagy is also accountable for dysfunctional mitochondria that raises Alzheimer’s pathology. Therefore, autophagic dysfunction might lead to the deposit of atypical proteins in the AD brain and manipulation of autophagy could be considered as an emerging therapeutic target. This review highlights the critical linkage of autophagy in the pathogenesis of AD, and avows a new insight to search for therapeutic target for blocking Alzheimer’s pathogenesis.     

Rosiglitazone treatment improves cardiac efficiency in hearts from diabetic mice

Isolated perfused hearts from type 2 diabetic (db/db) mice show impaired ventricular function, as well as altered cardiac metabolism. Assessment of the relationship between myocardial oxygen consumption (MVO(2)) and ventricular pressure-volume area (PVA) has also demonstrated reduced cardiac efficiency in db/db hearts. We hypothesized that lowering the plasma fatty acid supply and subsequent normalization of altered cardiac metabolism by chronic treatment with a peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist will improve cardiac efficiency in db/db hearts. Rosiglitazone (23 mg/kg body weight/day) was administered as a food admixture to db/db mice for five weeks. Ventricular function and PVA were assessed using a miniaturized (1.4 Fr) pressure-volume catheter; MVO(2) was measured using a fibre-optic oxygen sensor. Chronic rosiglitazone treatment of db/db mice normalized plasma glucose and lipid concentrations, restored rates of cardiac glucose and fatty acid oxidation, and improved cardiac efficiency. The improved cardiac efficiency was due to a significant decrease in unloaded MVO(2), while contractile efficiency was unchanged. Rosiglitazone treatment also improved functional recovery after low-flow ischemia. In conclusion, the present study demonstrates that in vivo PPARgamma-treatment restores cardiac efficiency and improves ventricular function in perfused hearts from type 2 diabetic mice.     

Unsymmetrically disubstituted urea derivatives: A potent class of antiglycating agents

A series of unsymmetrically disubstituted urea derivatives 1–28 has been synthesized and screened for their antiglycation activity in vitro. Compounds 26 (IC₅₀ = 4.26 ± 0.25 μM), 1 (IC₅₀ = 5.8 ± 0.08 μM), 22 (IC₅₀ = 4.26 ± 0.25 μM), 6 (IC₅₀ = 6.4 ± 0.02 μM), 5 (IC₅₀ = 6.6 ± 0.26 μM), 2 (IC₅₀ = 7.02 ± 0.31 μM), 3 (IC₅₀ = 7.14 ± 0.84 μM), 27 (IC₅₀ = 7.27 ± 0.36 μM), 4 (IC₅₀ = 8.16 ± 1.04 μM), 21 (IC₅₀ = 8.4 ± 0.15 μM), 23 (IC₅₀ = 9.0 ± 0.35 μM) and 13 (IC₅₀ = 15.22 ± 6.7 μM) showed an excellent antiglycation activity far better than the standard (rutin, IC₅₀ = 41.9 ± 2.3 μM). This study thus provides a series of potential molecules for further studies of antiglycation agents.