Dementia is a syndrome characterized by the development of multiple cognitive deficits and behavioral changes that leads to impairment of functional activities. There are primary degenerative, progressive and irreversible dementias, and other dementias resulting from a progressive but potentially reversible dementia of secondary origin.

Vascular dementia (VaD) is the most prevalent form of secondary dementia and the second most common of all dementias. The present paper aims to define guidelines on the basic principles for treating patients with suspected VaD (and vascular cognitive impairment - no dementia) using an evidence-based approach. The material was retrieved and selected from searches of databases (Medline, Scielo, Lilacs), preferentially from the last 15 years, to propose a systematic way to assess cognition, function and behavior, and disease severity staging, with instruments adapted for our milieu, and diagnosis disclosure. The present proposal contributes to the definition of standard diagnostic criteria for VaD based on various levels of evidence. It is noteworthy that only around half of the population of patients with vascular cognitive impairment present with dementia, which calls for future proposals defining diagnostic criteria and procedures for this condition.

This paper reports on development of a system consisting of a portable sequential injector coupled with potentiometric unit for sensing of chlorpheniramine (CPA), based on the reaction of CPA with potassium permanganate in acidic media. Various experimental conditions affecting the potential intensity were studied and incorporated into the procedure. Under the optimum conditions, linear relationship between the CPA concentration and peak area was obtained for the concentration range of 0.1-50 ppm. The method reflects good recovery with relative standard deviation (RSD)<3%. The detection limit was 0.05 ppm. The developed method was successfully applied for determination of CPA in pure form and in pharmaceutical dosage forms. The results, obtained using the method, are in accord with the results of the British pharmacopoeia method. In addition to its accuracy and precision, the method has the advantages of being simple, inexpensive and rapid.

Using our method for selectively detecting the response of intratumor quiescent (Q) cells to irradiation, the Q cells was shown to have a much larger hypoxic fraction (HF) than total (= proliferating (P) + Q) tumor cell population irrespective of the p53 status of tumor cells. However, the size of the HF was clearly less than 100%, meaning the Q cell population was never fully hypoxic. Thus, the dependency of the radio-sensitivity and recovery capacity from radiation-induced damage on p53 status was investigated in pimonidazole-unlabeled oxygenated Q tumor cells.

Much like replicative senescence, the irreversible cell-cycle arrest induced by eroded telomeres, accelerated senescence occurs when replicative cells suffer irreparable DNA double-strand breaks (DSBs). Along with apoptosis and necrosis, senescence is a desirable outcome in cancer treatment with ionizing radiation (IR) or chemotherapy. In both normal and cancer cells, DSBs promote the assembly of IR-induced foci (IRIF), domains of modified chromatin that serve a key role in DNA damage signaling. IRIF persistence is a critical determinant of accelerated senescence, making drugs that promote persistent IRIF an attractive strategy to sensitize cancer to genotoxic therapy. As an IRIF reporter, we have expressed an inducible green fluorescent protein (GFP) fusion to the IRIF-binding domain (IBD) of 53BP1 (GFP-IBD) in the breast cancer cell line MCF7. Within minutes of exposure to IR, the GFP-IBD relocalizes to form fluorescent nuclear foci, which disperse within several hours. A pair of high-content screening assays for IRIF formation and persistence were established in multiwell plates based on imaging and quantifying GFP-IBD foci per Hoechst-stained MCF7 nucleus at 2 hours and 24 hours. Using the ataxia telangiectasia-mutated inhibitor CGK733 to block IRIF formation and the topoisomerase II inhibitor etoposide to prevent IRIF resolution, we obtained a Z' >0.8 both for IRIF formation at 2 hours and IRIF persistence at 24 hours. Screening the diverse drugs and natural products in the National Cancer Institute Developmental Therapeutics Program Approved Oncology Drugs Set, the National Institutes of Health Clinical Collection, and the MicroSource Spectrum Collection yielded multiple hits that significantly delayed IRIF resolution. Secondary screening suggested some of these otherwise nontoxic drugs also enhance accelerated senescence, indicating strong potential for their repurposing as radiation sensitizers to improve the efficacy of cancer therapy.

The remarkable health benefits of the chemical cocktails occluded within Vites vinefera (grapes) have been broadly used as dietary supplements and as natural pharmaceuticals in the treatment of various diseases including human cancer. Current discovery demonstrates the rapid formation of gold nanoparticles with the phytochemicals present in grapes, which serve a dual role as synergistic reducing agents to reduce gold salts into gold nanoparticles and also as stabilizers to provide a robust coating on the gold nanoparticles in a single step. Furthermore, the grape-generated gold nanoparticles (GAuNPs), have demonstrated remarkable in vitro stability on specific functionalization with peptides (GSH) and thiol-containing compounds (lipoic acid) followed by the induction of cell-specific response. In addition, the grape-generated gold nanoparticles (GAuNPs, GSH-GAuNPs, LA-GAuNPs) have demonstrated remarkable affinity towards human breast cancer cells (HBL-100) in the present study. These studies thus signified the cellular internalization of GAuNPs and its conjugates by transmission electron microscopy through endocytosis into cancer cells. Notably, at higher concentration of gold nanoparticles conjugate, there was an asymmetric accumulation of gold nanoparticles in the periphery of the cell nucleus of the HBL-100 cells which was confirmed by fluorescence microscopy. Other than gold salts, no "manmade" chemicals are used in this truly biogenic, green nanotechnological process which thereby paves the way for outstanding opening for their application in molecular imaging and cancer therapy.

Cardiac allograft vasculopathy (CAV) is a major complication after heart transplantation, requiring frequent surveillance angiography. Though cardiac angiography is the gold standard, it is insensitive in detecting transplant vasculopathy and invasive. Perfusion MRI provides a noninvasive alternative and possibly a useful modality for studying CAV. We sought to compare the accuracy of qualitative perfusion MRI to coronary angiography in detecting CAV.

Interleukin-15 (IL-15) is a cytokine that is highly expressed in skeletal muscle. In addition to its well-characterized effects on innate immunity, IL-15 has been proposed to modulate skeletal muscle and adipose tissue mass, as well as insulin sensitivity. In the present study, an IL-15 gain-of-function model, transgenic mice with skeletal muscle-specific oversecretion of IL-15 (IL-15 Tg mice), was utilized to test the hypotheses that IL-15 promotes insulin sensitivity and resistance to diet-induced obesity (DIO) by increasing circulating adiponectin levels, and that IL-15 regulates skeletal muscle metabolism without inducing overt muscle hypertrophy. Compared to closely related control mice, IL-15 Tg mice exhibited lower total body fat following high-fat feeding, lower intra-abdominal fat following both low- and high-fat feeding, and greater insulin sensitivity. However, this was not accompanied by increased total or high molecular weight serum adiponectin levels in IL-15 Tg mice. While overall lean body mass did not differ, IL-15 Tg mice exhibited increased mass of the oxidative soleus muscle, and increased expression of mRNA encoding the slow isoform of troponin I (TnnI 1) in the predominately glycolytic extensor digitorum longus muscle. Skeletal muscle tissue from IL-15 Tg mice also exhibited alterations in the expression of several genes associated with fatty acid metabolism, such as SIRT1, SIRT4, and uncoupling protein 2 (UCP2). These findings suggest changes in oxidative metabolism, rather than induction of adiponectin expression, appear to be responsible for the DIO-resistant and more insulin-sensitive phenotype of IL-15 Tg mice.

Left main coronary artery (LMCA) bifurcation and heavily calcified lesions are common and challenging to treat percutaneously. Rotational atherectomy (RA) may be beneficial in this setting to facilitate stent placement though direct supporting evidence is lacking. This study sought to analyze patients who underwent RA of the LMCA.

The vitreous transition is characterized by a freezing of atomic degrees of freedom at a temperature Tg depending on the heating and cooling rates. A kinetic origin is generally attributed to this phenomenon instead of a thermodynamic one which we develop here. Completed homogeneous nucleation laws reflecting the energy saving due to Fermi energy equalization of nascent crystals and their melt are used. They are applied to bulk metallic glasses and extended to inorganic glasses and polymers. A transition T*g among various Tg corresponds to a crystal homogeneous nucleation temperature, leading to a preliminary formation of a cluster distribution during the relaxation time preceding the long steady-state nucleation time of crystals in small samples. The thermally-activated energy barrier ΔG*2ls/kBT at T*g for homogeneous nucleation is nearly the same in all glass-forming melts and determined by similar values of viscosity and a thermally-activated diffusion barrier from melt to cluster. The glass transition T*g is a material constant and a linear function of the energy saving associated with charge transfers from nascent clusters to the melt. The vitreous transition and the melting temperatures alone are used to predict the free-volume disappearance temperature equal to the Vogel-Fulcher-Tammann temperature of fragile glass-forming melts, in agreement with many viscosity measurements. The reversible thermodynamic vitreous transition is determined by the disappearance temperature T*g of the fully-relaxed enthalpy Hr that is not time dependent; the observed specific heat jump at T*g is equal to the proportionality coefficient of Hr with (T*g - Ta) for T ≤ T*g as expected from the enthalpy excess stored by a quenched undercooled melt at the annealing temperature Ta and relaxed towards an equilibrium vitreous state. However, the heat flux measurements found in literature over the last 50 years only gave an out-of-equilibrium Tg since the enthalpy is continuous at T*g without visible heat jump.

The present study describes a simple and highly selective method for separation, preconcentration and spectrophotometric determination of extremely low concentrations of lead. It is based on flotation of a complex of Pb2+ ions and Alizarin yellow between aqueous and n-hexane interface at pH = 6. The proposed procedure is also applied for determination of lead in both tap water and prepared sea water samples. Beer's Law was obeyed over the concentration range of 3.86 × 10-8 To 8.20 × 10-7 molL-1 (8-170 ngmL-1) with an apparent molar absorptivity of 1.33 × 106 molL-1 cm-1 for a 100 mL aliquot of the water sample. The detection limit (n = 10) was 8.7 × 10-9 molL-1 (1.0 ngmL-1) and the Relative standard deviation (R.S.D), (n = 10) for 7.2 × 10-7 molL-1 (150 ngmL-1) of Pb (II) was 4.36%. A notable advantage of the method is that the determination of Pb (II) is free from the interference of almost all cations and ions found in the environment and waste water samples. The determination of Pb (II) in tap and synthetic seawater samples was also carried out by the present method. The results were satisfactorily comparable so that the applicability of the proposed method was confirmed to the real samples.

This study investigated the effect of the serotonin selective reuptake inhibitors (SSRIs) fluoxetine, sertraline, fluvoxamine and the tricyclic antidepressant (TCA) impiramine on oxidative stress in brain and liver induced by lipopolysaccharide administration in mice. Each drug was administered subcutaneously at doses of 10 or 20 mg/kg, for two days prior to intraperitoneal (i.p.) administration of lipopolysaccharide E (LPS: 200 µg/kg). Mice were euthanized 4 h after administration of the lipopolysaccharide. Lipid peroxidation (malondialdehyde; MDA), reduced glutathione (GSH) and nitric oxide (nitrite/nitrate) concentrations were measured in brain and liver. Results: The administration of lipopolysaccharide increased oxidative stress in brain and liver; it increased brain MDA by 36.1 and liver MDA by 159.8 %. GSH decreased by 34.1 % and 64.8 % and nitric oxide increased by 78.7 % and 103.8 % in brain and liver, respectively. In brain, MDA decreased after the administration of sertraline and by the lower dose of fluoxetine or fluvoxamine, but increased after the higher dose of imipramine. Reduced glutathione increased after sertraline, fluvoxamine and the lower dose of fluoxetine or imipramine. Nitric oxide decreased by sertraline, fluoxetine, fluvoxamine and by the lower dose of imipramine. In the liver, all drugs decreased MDA and increased GSH level. Nitric oxide is decreased by sertraline, fluvoxamine and by the lower dose of fluoxetine or imipramine. It is concluded that, during mild systemic inflammatory illness induced by peripheral bacterial endotoxin injection, the SSRIs fluoxetine, sertraline and fluvoxamine reduced, while the TCA impiramine increased oxidative stress induced in the brain. The SSRIs as well as imipramine reduced oxidative stress due to lipopolysaccharide in liver tissue.

The ability of an aqueous extract of the rhizomes of Sansevieria liberica to protect against carbon tetrachloride induced liver injury was investigated in Wistar albino rats. The carbon tetrachloride was prepared 1:5 (v:v) in olive oil, and administered subcutaneously at 1 mL/kg body weight. The extract was administered to both normal and carbon tetrachloride treated rats at 100, 200 and 300 mg/kg. On gas chromatographic analysis of the extract, twenty nine known flavonoids were detected, consisting mainly of 31.94 % apigenin, 20.66 % quercetin, 11.28 % kaempferol, 5.99 % naringenin, 5.83 % (-)-epicatechin, 3.69 % biochanin, 3.58 % (+)-catechin, 2.72 % diadzein, 2.20 % ellagic acid, 2.04 % butein. Compared to test control, the treatment dose dependently produced significantly (P<0.05) lower alkaline phosphatase, aspartate transaminase and alanine transaminase activities. The plasma total bilirubin and total protein levels of the test animals were lower though not significantly. The hepatic histopathological studies showed that carbon tetrachloride caused fatty degeneration of hepatocytes, which was inhibited by pre-treatment with the extract; thus, confirming the results of the biochemical studies. The results of this study indicated that treatment with the plant extracts protects the liver against carbon tetrachloride induced hepatotoxicity. This supports the use of Sansevieria liberica in traditional health care for managing liver problems.

Dang Gui Bu Xue Tang (DBT), a Chinese medicinal decoction contains Radix Angelicae sinensis (Danggui) and Radix Astragali (Huangqi) at a ratio of 1 : 5, is used commonly for treating women's ailments. This study was conducted to explore the effects of this preparation on insulin resistance in rats fed with 6-week diet containing 60% fructose. Similar to the action of rosiglitazone (4 mg kg(-1) per day by an oral administration), repeated oral administration of DBT (2.5 g kg(-1) per day) for 14 days was found to significantly alleviate the hyperglycemia but made no influence on plasma lipid profiles nor weight gain in fructose chow-fed rats. Also, the higher degree of insulin resistance as measured by homeostasis model assessment of basal insulin resistance in fructose chow-fed rats was significantly decreased by repeated DBT treatment. DBT displays the characteristic of rosiglitazone by increasing the whole-body insulin sensitivity in fructose chow-fed rats after 2-week treatment, as evidenced by the marked elevation of composite whole-body insulin sensitivity index during the oral glucose tolerance test. DBT improves insulin sensitivity through increased post-receptor insulin signaling mediated by enhancements in insulin receptor substrate-1-associated phosphatidylinositol 3-kinase step and glucose transporter subtype 4 translocation in soleus muscles of animals exhibiting insulin resistance. DBT is therefore proposed as potentially useful adjuvant therapy for patients with insulin resistance and/or the patients who wish to increase insulin sensitivity.

In this study, 4,7-dimethoxy-5-methyl-l,3-benzodioxole (SY-1) was isolated from three different sources of dried fruiting bodies of Antrodia camphorate (AC). AC is a medicinal mushroom that grows on the inner heartwood wall of Cinnamomum kanehirai Hay (Lauraceae), an endemic species that is used in Chinese medicine for its anti-tumor and immunomodulatory properties. In this study, we demonstrated that SY-1 profoundly decreased the proliferation of human colon cancer cells (COLO 205) through G0/G1 cell-cycle arrest (50-150 μM) and induction of apoptosis (>150 μM). Cell-cycle arrest induced by SY-1 was associated with a significant increase in levels of p53, p21/Cip1 and p27/Kip1, and a decrease in cyclins D1, D3 and A. In contrast, SY-1 treatment did not induce significant changes in G0/G1 phase cell-cycle regulatory proteins in normal human colonic epithelial cells (FHC). The cells were cultured in soft agar to evaluate anchorage-independent colony formation, and we found that the number of transformed colonies was significantly reduced in the SY-1-treated COLO 205 cells. These findings demonstrate for the first time that SY-1 inhibits human colon cancer cell proliferation through inhibition of cell growth and anchorage-independent colony formation in soft agar. However, the detailed mechanisms of these processes remain unclear and will require further investigation.

Environment influences brain development, neurogenesis and, possibly, vulnerability to neurodegenerative disease. We retrospectively examined the brains of aged rhesus monkeys reared during early life in either small cages or larger, "standard-sized" cages; all monkeys were subsequently maintained in standard-sized cages during adulthood. Aged monkeys reared in smaller cages exhibited significantly greater β-amyloid plaque deposition in the neocortex and a significant reduction in synaptophysin immunolabeling in cortical regions compared to aged monkeys reared in standard-sized cages (p<0.001 and p<0.05, respectively). These findings suggest that early environment may influence brain structure and vulnerability to neurodegenerative changes in late life.

In Bacillus subtilis, the KipI protein is a regulator of the phosphorelay governing the onset of sporulation. KipI binds the relevant sensor histidine kinase, KinA, and inhibits the autophosphorylation reaction. Gene homologues of kipI are found almost ubiquitously throughout the bacterial kingdom and are usually located adjacent to, and often fused with, kipA gene homologues. In B. subtilis, the KipA protein inhibits the antikinase activity of KipI thereby permitting sporulation. We have used a combination of biophysical techniques in order to understand the domain structure and shape of the KipI-KipA complex and probe the nature of the interaction. We also have solved the crystal structure of TTHA0988, a Thermus thermophilus protein of unknown function that is homologous to a KipI-KipA fusion. This structure, which is the first to be described for this class of proteins, provides unique insight into the nature of the KipI-KipA complex. The structure confirms that KipI and KipA are proteins with two domains, and the C-terminal domains belong to the cyclophilin family. These cyclophilin domains are positioned in the complex such that their conserved surfaces face each other to form a large "bicyclophilin" cleft. We discuss the sequence conservation and possible roles across species of this near-ubiquitous protein family, which is poorly understood in terms of function.

We hypothesized that bone marrow-derived mononuclear cells (BMDMC) would attenuate the remodeling process in a chronic allergic inflammation model. C57BL/6 mice were assigned to two groups. In OVA, mice were sensitized and repeatedly challenged with ovalbumin. Control mice (C) received saline under the same protocol. C and OVA were further randomized to receive BMDMC (2 × 10⁶) or saline intravenously 24 h before the first challenge. BMDMC therapy reduced eosinophil infiltration, smooth muscle-specific actin expression, subepithelial fibrosis, and myocyte hypertrophy and hyperplasia, thus causing a decrease in airway hyperresponsiveness and lung mechanical parameters. BMDMC from green fluorescent protein (GFP)-transgenic mice transplanted into GFP-negative mice yielded lower engraftment in OVA. BMDMC increased insulin-like growth factor expression, but reduced interleukin-5, transforming growth factor-β, platelet-derived growth factor, and vascular endothelial growth factor mRNA expression. In conclusion, in the present chronic allergic inflammation model, BMDMC therapy was an effective pre-treatment protocol that potentiated airway epithelial cell repair and prevented inflammatory and remodeling processes.

Full-Parasites (http://fullmal.hgc.jp/) is a transcriptome database of apicomplexa parasites, which include Plasmodium and Toxoplasma species. The latest version of Full-Parasites contains a total of 105,786 EST sequences from 12 parasites, of which 5925 full-length cDNAs have been completely sequenced. Full-Parasites also contain more than 30 million transcription start sites (TSS) for Plasmodium falciparum (Pf) and Toxoplasma gondii (Tg), which were identified using our novel oligo-capping-based protocol. Various types of cDNA data resources were interconnected with our original database functionalities. Specifically, in this update, we have included two unique RNA-Seq data sets consisting of 730 million mapped RNA-Seq tags. One is a dataset of 16 time-lapse experiments of cultured bradyzoite differentiation for Tg. The other dataset includes 31 clinical samples of Pf. Parasite RNA was extracted together with host human RNA, and the extracted mixed RNA was used for RNA sequencing, with the expectation that gene expression information from the host and parasite would be simultaneously represented. By providing the largest unique full-length cDNA and dynamic transcriptome data, Full-Parasites is useful for understanding host-parasite interactions and will help to eventually elucidate how monophyletic organisms have evolved to become parasites by adopting complex life cycles.

RegulonDB (http://regulondb.ccg.unam.mx/) is the primary reference database of the best-known regulatory network of any free-living organism, that of Escherichia coli K-12. The major conceptual change since 3 years ago is an expanded biological context so that transcriptional regulation is now part of a unit that initiates with the signal and continues with the signal transduction to the core of regulation, modifying expression of the affected target genes responsible for the response. We call these genetic sensory response units, or Gensor Units. We have initiated their high-level curation, with graphic maps and superreactions with links to other databases. Additional connectivity uses expandable submaps. RegulonDB has summaries for every transcription factor (TF) and TF-binding sites with internal symmetry. Several DNA-binding motifs and their sizes have been redefined and relocated. In addition to data from the literature, we have incorporated our own information on transcription start sites (TSSs) and transcriptional units (TUs), obtained by using high-throughput whole-genome sequencing technologies. A new portable drawing tool for genomic features is also now available, as well as new ways to download the data, including web services, files for several relational database manager systems and text files including BioPAX format.