FORMULATION AND EVALUATION OF TELMISARTAN FAST DISSOLVING TABLETS USING JACK FRUIT SEED STARCH AS SUPERDISINTEGRANT

Objective: The main objective of the current study is to enhance the solubility of Biopharmaceutical Classification System (BCS) Class-II drug Telmisartan using jack fruit seed starch as super disintegrant which increases drug release. Methods: Starches were extracted using alkali technique using sodium hydroxide at 0.1%, 0.25%, and 0.5% concentrations and water from Jack fruit seed powder. These starches were evaluated for various phytochemical and physicochemical tests. Fast dissolving tablets were prepared using Telmisartan, jack fruit seed starch and Croscarmellose sodium in various concentrations using wet granulation technique. Various pre and post-compression parameters were evaluated along with in vitro drug release studies, characterization studies like Fourier Transform Infra-Red spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD) and accelerated stability studies. Results: Phytochemical tests revealed the presence of only starch in all the extracts. The starch prepared from 0.1% sodium hydroxide (JFS2) showed best physicochemical properties. From in vitro dissolution studies, it was observed that formulations F5 and F11 containing 15% w/w of JFS2 and 15% w/w of croscarmellose sodium showed faster disintegration and increased dissolution rate compared with other formulations. FTIR and DSC studies showed that there were no major interactions among drug and excipients. XRD studies revealed the nature of formulations. Accelerated stability studies revealed the stability of tablets. Conclusion: Thus, the tablets prepared using Jack fruit seed starch revealed the super disintegrant property of starch

FITsense: employing multi-modal sensors in smart homes to predict falls.

As people live longer, the increasing average age of the population places additional strains on our health and social services. There are widely recognised benefits to both the individual and society from supporting people to live independently for longer in their own homes. However, falls in particular have been found to be a leading cause of the elderly moving into care, and yet surprisingly preventative approaches are not in place; fall detection and rehabilitation are too late. In this paper we present FITsense, which is building a Smart Home environment to identify increased risk of falls for residents, and so allow timely interventions before falls occurs. An ambient sensor network, installed in the Smart Home, identifies low level events taking place which is analysed to generate a resident’s profile of activities of daily living (ADLs). These ADL profiles are compared to both the resident’s typical profile and to known “risky” profiles to allow evidence-driven intervention recommendations. Human activity recognition to identify ADLs from sensor data is a key challenge. Here we compare a windowing-based and a sequence-based event representation on four existing datasets. We find that windowing works well, giving consistent performance but may lack sufficient granularity for more complex multi-part activities

Rotation in an Enantiospecific Self‐Assembled Array of Molecular Raffle Wheels

Tailored nano-spaces can control enantioselective adsorption and molecular motion. We report on the spontaneous assembly of a dynamic system—a rigid kagome network with each pore occupied by a guest molecule—employing solely 2,6-bis(1H-pyrazol-1-yl)pyridine-4-carboxylic acid on Ag(111). The network cavity snugly hosts the chemically modified guest, bestows enantiomorphic adsorption and allows selective rotational motions. Temperature-dependent scanning tunnelling microscopy studies revealed distinct anchoring orientations of the guest unit switching with a 0.95 eV thermal barrier. H-bonding between the guest and the host transiently stabilises the rotating guest, as the flapper on a raffle wheel. Density functional theory investigations unravel the detailed molecular pirouette of the guest and how the energy landscape is determined by H-bond formation and breakage. The origin of the guest\u27s enantiodirected, dynamic anchoring lies in the specific interplay of the kagome network and the silver surface

IAPAR 8 - Rio Negro, nova cultivar de feijoeiro

After five cycles of selection under  field conditions, a new bean (Phaseolus vulgaris L.) cultivar was obtained, ‘IAPAR 8 - Rio Negro', which has black seed coat, upright growth habit, 92 days from emergence to maturity, and field resistance to all physiological races of the fungus Colletotrichum lindemuthianum known to the moment. Its 1000 seeds weight is around 210 g, it shows wide adaptation, and yields 3000 kg/ha under good edaphic and climatic conditions. Yield data of the new cultivar, obtained from three different localities in the state of Paraná, Brazil, and its main characteristics are presented.Após cinco ciclos de seleção em condições de campo, foi criada a nova cultivar de feijoeiro (Phaseolus vulgaris L.) 'IAPAR 8 - Rio Negro', de tegumento de cor preta, de porte ereto, de ciclo médio de 92 dias, e que apresenta resistência de campo a todas raças fisiológicas do fungo Colletotrichum lindemuthianum conhecidas até o momento. Seu peso de mil sementes é em torno de 210 gramas, tem ampla adaptação e atinge produtividade de até 3.000 kg/ha em boas condições edafoclimáticas. Resultados de produção da nova variedade, obtidas em três diferentes locais do Estado do Paraná e suas principais características, são apresentados

ApoB100/LDLR-/- Hypercholesterolaemic Mice as a Model for Mild Cognitive Impairment and Neuronal Damage

Recent clinical findings support the notion that the progressive deterioration of cholesterol homeostasis is a central player in Alzheimer's disease (AD). Epidemiological studies suggest that high midlife plasma total cholesterol levels are associated with an increased risk of AD. This paper reports the plasma cholesterol concentrations, cognitive performance, locomotor activity and neuropathological signs in a murine model (transgenic mice expressing apoB100 but knockout for the LDL receptor [LDLR]) of human familial hypercholesterolaemia (FH). From birth, these animals have markedly elevated LDL-cholesterol and apolipoprotein B100 (apoB100) levels. These transgenic mice were confirmed to have higher plasma cholesterol concentrations than wild-type mice, an effect potentiated by aging. Further, 3-month-old transgenic mice showed cholesterol (total and fractions) concentrations considerably higher than those of 18-month-old wild-type mice. The hypercholesterolaemia of the transgenic mice was associated with a clear locomotor deficit (as determined by rotarod, grip strength and open field testing) and impairment of the episodic-like memory (determined by the integrated memory test). This decline in locomotor activity and cognitive status was associated with neuritic dystrophy and/or the disorganization of the neuronal microtubule network, plus an increase in astrogliosis and lipid peroxidation in the brain regions associated with AD, such as the motor and lateral entorhinal cortex, the amygdaloid basal nucleus, and the hippocampus. Aortic atherosclerotic lesions were positively correlated with age, although potentiated by the transgenic genotype, while cerebral β-amyloidosis was positively correlated with genetic background rather than with age. These findings confirm hypercholesterolaemia as a key biomarker for monitoring mild cognitive impairment, and shows these transgenic mice can be used as a model for cognitive and psycho-motor decline

Structural Characterization of CYP51 from Trypanosoma cruzi and Trypanosoma brucei Bound to the Antifungal Drugs Posaconazole and Fluconazole

Chagas Disease is caused by kinetoplastid protozoa Trypanosoma cruzi, whose sterols resemble those of fungi, in both composition and biosynthetic pathway. Azole inhibitors of sterol 14α-demethylase (CYP51), such as fluconazole, itraconazole, voriconazole, and posaconazole, successfully treat fungal infections in humans. Efforts have been made to translate anti-fungal azoles into a second-use application for Chagas Disease. Ravuconazole and posaconazole have been recently proposed as candidates for clinical trials with Chagas Disease patients. However, the widespread use of posaconazole for long-term treatment of chronic infections may be limited by hepatic and renal toxicity, a requirement for simultaneous intake of a fatty meal or nutritional supplement to enhance absorption, and cost. To aid our search for structurally and synthetically simple CYP51 inhibitors, we have determined the crystal structures of the CYP51 targets in T. cruzi and T. brucei, both bound to the anti-fungal drugs fluconazole or posaconazole. The structures provide a basis for a design of new drugs targeting Chagas Disease, and also make it possible to model the active site characteristics of the highly homologous Leishmania CYP51. This work provides a foundation for rational synthesis of new therapeutic agents targeting the three kinetoplastid parasites

In Vitro Downregulation of Matrix Metalloproteinase-9 in Rat Glial Cells by CCR5 Antagonist Maraviroc: Therapeutic Implication for HIV Brain Infection

BACKGROUND: Matrix metalloproteinases (MMPs) released by glial cells are important mediators of neuroinflammation and neurologic damage in HIV infection. The use of antiretroviral drugs able to combat the detrimental effect of chronic inflammation and target the exaggerated MMP activity might represent an attractive therapeutic challenge. Recent studies suggest that CCR5 antagonist maraviroc (MVC) exerts immunomodulant and anti-inflammatory activity beyond its anti-HIV properties. We investigated the in vitro effect of MVC on the activity of MMPs in astrocyte and microglia cultures. METHODOLOGY/PRINCIPAL FINDINGS: Primary cultures of rat astrocytes and microglia were activated by exposure to phorbol myristate acetate (PMA) or lypopolysaccharide (LPS) and treated in vitro with MVC. Culture supernatants were subjected to gelatin zymography and quantitative determination of MMP-9 and MMP-2 was done by computerized scanning densitometry. MMP-9 levels were significantly elevated in culture supernatants from both LPS- and PMA-activated astrocytes and microglia in comparison to controls. The treatment with MVC significantly inhibited in a dose-dependent manner the levels and expression of MMP-9 in PMA-activated astrocytes (p<0,05) and, to a lesser extent, in PMA-activated microglia. By contrast, levels of MMP-2 did not significantly change, although a tendency to decrease was seen in PMA-activated astrocytes after treatment with MVC. The inhibition of levels and expression of MMP-9 in PMA-activated glial cells did not depend on cytotoxic effects of MVC. No inhibition of MMP-9 and MMP-2 were found in both LPS-activated astrocytes and microglia. CONCLUSIONS: The present in vitro study suggests that CCR5 antagonist compounds, through their ability to inhibit MMP-9 expression and levels, might have a great potential for the treatment of HIV-associated neurologic damage

Tissue inhibitor of metalloproteinases-1 protects human neurons from staurosporine and HIV-1-induced apoptosis: mechanisms and relevance to HIV-1-associated dementia

HIV-1-associated dementia (HAD)-relevant proinflammatory cytokines robustly induce astrocyte tissue inhibitor of metalloproteinases-1 (TIMP-1). As TIMP-1 displays pleotropic functions, we hypothesized that TIMP-1 expression may serve as a neuroprotective response of astrocytes. Previously, we reported that chronically activated astrocytes fail to maintain elevated TIMP-1 expression, and TIMP-1 levels are lower in the brain of HAD patients; a phenomenon that may contribute to central nervous system pathogenesis. Further, the role of TIMP-1 as a neurotrophic factor is incompletely understood. In this study, we report that staurosporine (STS) and HIV-1ADA virus, both led to induction of apoptosis in cultured primary human neurons. Interestingly, cotreatment with TIMP-1 protects neurons from apoptosis and reverses neuronal morphological changes induced by these toxins. Further, the anti-apoptotic effect was not observed with TIMP-2 or -3, but was retained in a mutant of the N-terminal TIMP-1 protein with threonine-2 mutated to glycine (T2G) that is deficient in matrix metalloproteinase (MMP)-1, -2 and -3 inhibitory activity. Therefore, the mechanism is specific to TIMP-1 and partially independent of MMP-inhibition. Additionally, TIMP-1 modulates the Bcl-2 family of proteins and inhibits opening of mitochondrial permeability transition pores induced by HIV-1 or STS. Together, these findings describe a novel function, mechanism and direct role of TIMP-1 in neuroprotection, suggesting its therapeutic potential in HAD and possibly in other neurodegenerative diseases

A Polyadenylation Factor Subunit Implicated in Regulating Oxidative Signaling in Arabidopsis thaliana

BACKGROUND: Plants respond to many unfavorable environmental conditions via signaling mediated by altered levels of various reactive oxygen species (ROS). To gain additional insight into oxidative signaling responses, Arabidopsis mutants that exhibited tolerance to oxidative stress were isolated. We describe herein the isolation and characterization of one such mutant, oxt6. METHODOLOGY/PRINCIPAL FINDINGS: The oxt6 mutation is due to the disruption of a complex gene (At1g30460) that encodes the Arabidopsis ortholog of the 30-kD subunit of the cleavage and polyadenylation specificity factor (CPSF30) as well as a larger, related 65-kD protein. Expression of mRNAs encoding Arabidopsis CPSF30 alone was able to restore wild-type growth and stress susceptibility to the oxt6 mutant. Transcriptional profiling and single gene expression studies show elevated constitutive expression of a subset of genes that encode proteins containing thioredoxin- and glutaredoxin-related domains in the oxt6 mutant, suggesting that stress can be ameliorated by these gene classes. Bulk poly(A) tail length was not seemingly affected in the oxt6 mutant, but poly(A) site selection was different, indicating a subtle effect on polyadenylation in the mutant. CONCLUSIONS/SIGNIFICANCE: These results implicate the Arabidopsis CPSF30 protein in the posttranscriptional control of the responses of plants to stress, and in particular to the expression of a set of genes that suffices to confer tolerance to oxidative stress