Novartis

About: Novartis is a company organization based out in Basel, Switzerland. It is known for research contribution in the topics: Alkyl & Population. The organization has 41930 authors who have published 50566 publications receiving 1978996 citations. The organization is also known as: Novartis International AG.

Letters to the Editor: Linearization of dissolution rate curves by the Weibull distribution

Abstract: The quantitative interpretation of dissolution rate data is greatly facilitated by the application of a general mathematical expression which describes the entire curve in terms of meaningful parameters. In special case, the equation can be derived from a theoretical treatment of the process, e.g. the cube-root law or zero-order kinetics, see Wagner (1970). In the most general case of tablets, coated tablets, capsules, or sustained-release preparations, however, no such theoretical basis is available and a suitable function has to be found empirically. First-order kinetics were proposed by Gibaldi & Feldman (1967) and Wagner (1969) introduced the lognormal presentation for this purpose. Although these two models together describe most dissolution curves observed, they exclude each other and are, thus, of limited applicability: for example, see the discussion of Wagner (1970) relative to Figs. 20.2 and 20.3. A more general function which may be applied successfully to all common types of dissolution curves, was described by Weibull (1951). All characteristics of this distribution function are discussed in detail by Kao (1959) and Ruzicka (1962). A concise survey is given by Grant (1964). When applied to dissolution rate data, the Weibull equation expresses the accumulated fraction, m, of the material in solution at time t, by

Pyrimidine derivatives and processes for the preparation thereof

Abstract: There are described N-phenyl-2-pyrimidine-amine derivatives of formula I ##STR1## wherein R 1 is 4-pyrazinyl, 1-methyl-1H-pyrrolyl, amino- or amino-lower alkyl-substituted phenyl wherein the amino group in each case is free, alkylated or acylated, 1H-indolyl or 1H-imidazolyl bonded at a five-membered ring carbon atom, or unsubstituted or lower alkyl-substituted pyridyl bonded at a ring carbon atom and unsubstituted or substituted at the nitrogen atom by oxygen, R 2 , R 3 , R 9 , X, Y, n and R 10 are defined in claim 1 These compounds can be used, for example, in the therapy of tumoral diseases

FTY720 (fingolimod) in Multiple Sclerosis: therapeutic effects in the immune and the central nervous system

Abstract: FTY720 (fingolimod) is a first-in-class sphingosine 1-phosphate (S1P) receptor modulator that was highly effective in Phase II clinical trials for Multiple Sclerosis (MS). FTY720 is phosphorylated in vivo by sphingosine kinase-2 to form the active moiety FTY720-phosphate that binds to four of the five G protein-coupled S1P receptor subtypes. Studies using conditional S1P1 receptor-deficient and sphingosine kinase-deficient mice showed that the egress of lymphocytes from lymph nodes requires signalling of lymphocytic S1P1 receptors by the endogenous ligand S1P. The S1P mimetic FTY720-phosphate causes internalization and degradation of cell membrane-expressed S1P1, thereby antagonizing S1P action at the receptor. In models of human MS and demyelinating polyneuropathies, functional antagonism of lymphocytic S1P1 slows S1P-driven egress of lymphocytes from lymph nodes, thereby reducing the numbers of autoaggressive TH17 cells that recirculate via lymph and blood to the central nervous system and the sciatic/ischiatic nerves. Based on its lipophilic nature, FTY720 crosses the blood–brain barrier, and ongoing experiments suggest that the drug also down-modulates S1P1 in neural cells/astrocytes to reduce astrogliosis, a phenomenon associated with neurodegeneration in MS. This may help restore gap-junctional communication of astrocytes with neurons and cells of the blood–brain barrier. Additional effects may result from (down-) modulation of S1P3 in astrocytes and of S1P1 and S1P5 in oligodendrocytes. In conclusion, FTY720 may act through immune-based and central mechanisms to reduce inflammation and support structural restoration of the central nervous system parenchyma. Beyond the autoimmune indications, very recent studies suggest that short-term, low-dose administration of FTY720 could help treat chronic (viral) infections. Differential effects of the drug on the trafficking of naive, central memory and effector memory T cell subsets are discussed.

Neuropsychiatric symptoms in patients with Parkinson’s disease and dementia: frequency, profile and associated care giver stress

Abstract: Objective: To explore the profile of neuropsychiatric symptoms in patients with dementia associated with Parkinson’s disease (PDD). Methods: 537 patients with PDD drawn from an international multicentre clinical trial of rivastigmine were assessed using the 10-item Neuropsychiatric Inventory (NPI). A cluster analysis was used to investigate the inter-relationship of NPI items. Associations between the clusters and demographic and clinical variables were analysed. Results: 89% of the patients presented at least one symptom on the NPI, 77% had two or more symptoms and 64% had at least one symptom with a score ⩾4. The most common symptoms were depression (58%), apathy (54%), anxiety (49%) and hallucinations (44%). Patients with more severe dementia and advanced Parkinson’s disease had more neuropsychiatric symptoms. Nearly 60% of the care givers reported at least one NPI symptom to be of at least moderate severe distress. Five NPI clusters were identified: one group with few and mild symptoms (52%); a mood cluster (11%, high scores on depression, anxiety and apathy); apathy (24%; high apathy and low scores on other items); agitation (5%, high score on agitation and high total NPI score); and a psychosis cluster (8%; high scores on delusions and hallucinations). The psychosis and agitation clusters had the lowest Mini-Mental State Examination score and the highest Unified Parkinson’s Disease Rating Scale and care giver distress scores. Conclusion: Neuropsychiatric symptoms are common in patients with PDD. The profile of these symptoms differs from that in other types of dementia. Subgroups with different neuropsychiatric profiles were identified. These subgroups may be associated with distinct neurobiological changes, which should be explored in future studies.