Chemotherapy in Osteogenic Sarcoma

Progress in Clinical and Biological Research. 1982  |  Pubmed ID: 6983080

[Various Aspects of Leprosy Control in the Developing Countries of Southeastern Asia]

Zhurnal Mikrobiologii, Epidemiologii, I Immunobiologii. Oct, 1987  |  Pubmed ID: 3321772

Single and Multiple Dose Pharmacokinetics of Tenoxicam in the Elderly

European Journal of Clinical Pharmacology. 1988  |  Pubmed ID: 3266152

Fourteen elderly subjects (10 women, 4 men) with a mean age of 81 (SD 6.7) years and in need of anti-inflammatory drug treatment were given a single dose of 20 mg tenoxicam. After a drug-free interval of 5 weeks, multiple dose treatment with 20 mg tenoxicam once daily for 56 days was initiated. The single and multiple dose kinetics of tenoxicam were investigated after HPLC determination of tenoxicam in the plasma. The elimination half-life of tenoxicam ranged from 44 to 132 h (mean 71.9 h) with no significant difference between the single and multiple dosage regimens. Tenoxicam reached maximum plasma concentrations after 1.4 and 1.1 h, with values of 3.6 and 15.5 micrograms.ml-1, for the single and multiple dosage regimen respectively. The corresponding trough values (24-h values) were 1.8 and 11.7 micrograms.ml-1. A mean accumulation ratio of 5.1 was calculated. The mean increase in the area under the plasma concentration time curves at steady-state was 21% more than predicted from the initial single dose. This deviation from linearity was considered to be of minor clinical significance. The kinetics of tenoxicam in elderly were similar to that published for young healthy volunteers.

[Integrated Psychiatric Care Planning]

Tidsskrift for Den Norske Lægeforening : Tidsskrift for Praktisk Medicin, Ny Række. May, 1997  |  Pubmed ID: 9213982

In order to design an integrated plan for services, all long-term psychiatric patients in Trondheim were registered by professionals on both municipality and county level. Data were obtained from interviews with the patients, supplemented by information from professional personnel. Individual plans, including type and amount of services needed, were prepared for each patient anonymously, to form the basis of a mutually beneficial integrated plan for psychiatric services. A total of 507 patients were registered (0.5% of the population over 18 years). Studying individual patients and their needs makes it possible to make optimal use of limited resources. The sharing of knowledge improves cooperation and coordination, to the benefit of a neglected group of patients.

Chlorinated Pesticides and PCBs in Sediments and Molluscs from Freshwater Canals in the Hanoi Region

Environmental Pollution (Barking, Essex : 1987). 2001  |  Pubmed ID: 11291437

The concentrations of organochlorine pesticides and PCBs were determined in surface sediments and freshwater molluscs (Angulyagra sp.) from water canals in the region of Hanoi city. Results obtained show that the concentration of sigma DDT compounds in sediments range from 7 to 80 ng/g (dry weight) and from 6 to 864 ng/g (dry weight) in the soft tissues of molluscs. The concentrations of sigma DDTs were higher in populated sites and much lower in rural sites, indicating that the DDT has been used for mosquito control and not as a crop protection chemical. Hexachlocyclohexanes (HCHs) have also been widely used in the region but the current environmental concentrations are much lower than those of DDT's, which is due to the less persistence of those compounds. Polychlorinated biphenyls (PCBs) were measured, for example as aroclor 1254, in concentrations up to 40 ng/g (dry weight) and up to 76 ng/g (dry weight) in sediments and molluscs, respectively. Molluscs from water canals are a very popular food in the region. Taking into consideration the high DDT levels measured in these molluscs their consumption is worrisome and may expose the population to high levels of endocrine disrupting substances. Current PCB levels in sediments are lower than usually measured in industrialized countries. Therefore, PCB concentrations in aquatic molluscs are still also relatively low. These snails do not have enzyme ability to metabolize most of the CB congeners and, thus, are passive accumulators and a significant transfer pathway of CBs to consumers. Therefore, measures to phase out the use of these persistent and bioaccumulable chemicals should be adopted in order to prevent further environmental contamination.

Cephalometric Evaluation of the Effects of Pendulum Appliance on Various Vertical Growth Patterns and of the Changes During Short-term Stabilization

Clinical Orthodontics and Research. Feb, 2001  |  Pubmed ID: 11553081

The aim of this study was to evaluate the effects of the pendulum appliance in dental Class II patients with varying vertical growth patterns and to evaluate the changes during the short-term stabilization period of 3 months. The sample (n=30) was divided into two groups based on their FMA degrees. The high-angle group consisted of 14 patients (10 girls and 4 boys) and had a mean age of 157.7+/-8.0 months. The low-angle group consisted of 16 patients (8 girls and 8 boys) and had a mean age of 155.5+/-18.6 months. Pretreatment, posttreatment and poststabilization cephalometric radiographs were obtained to measure the changes. Mann-Whitney U and Wilcoxon tests were used for statistical evaluation. The amount of upper molar distalization was 5.9 mm (p<0.001) in the high-angle group and 1 mm (p<0.001) in the low-angle group, showing no intergroup difference. The amount of anchorage loss at the second premolars was 4.8 mm (p<0.001) in the high-angle group and 6.6 mm (p<0.001) in the low-angle group. Upper incisors moved anteriorly for 2.1 mm (p<0.05) in the high-angle group and 4.1 mm (p<0.001) in the low-angle group. Intergroup difference was statistically significant (p<0.001). During the stabilization period, 1.5 mm of anchorage loss was measured at the upper molar region in the high-angle group and 1.7 mm of anchorage loss was measured at the upper molar region in the low-angle group. During the stabilization period, upper second premolars and incisors tended to move back to their original places. The results of this study showed that pendulum appliance could move the upper molars distally in a short period of time without depending on the patient compliance. Care should be taken to prevent anchorage loss and to stabilize the upper molars for, at least, 3 months.

The Essentiality of Bcl-2, PKC and Proteasome-ubiquitin Complex Activations in the Neuroprotective-antiapoptotic Action of the Anti-Parkinson Drug, Rasagiline

Biochemical Pharmacology. Oct, 2003  |  Pubmed ID: 14555244

The anti-Parkinson drug, rasagiline, a irreversible propargyl possessing monoamine oxidase B inhibitor can protect neurons in vitro and in vivo from a variety of neurotoxic insults including SIN-1, glutamate, the parkinsonism inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, N-methyl-(R)-salsolinol and including beta amyloid protein. Recent studies have shown that rasagiline rapidly modulates intracellular signaling pathways involved in cell survival and death. Specifically rasagiline activates Bcl-2, Bcl-xl, protein kinase C (PKC) and reduces Bax in a variety of cells including PC-12 and neuroblastoma human dopamine derived SH-SY5Y cells. These enzymes play key roles in cellular events including modulation of apoptotic processes, neuronal plasticity and amyloid precursor protein processing. This pharmacological action of rasagiline is also associated with the prevention of the neurotoxin induced fall in mitochondrial membrane potential, opening of mitochondria permeability transition pore, activation of proteasome-ubiquitin complex, inhibition of cytochrome c release and prevention of caspase 3 activation, similar to the actions of cyclosporin A or Bcl-2 over expression in SH-SY5Y cells. Rasagiline and its various derivatives induces PKC dependent release of soluble amyloid precursor protein alpha and which is blocked by inhibitors of alpha-secretase, PKC and MAPK-dependent signaling. Structure-activity relationship with various propargyl containing derivatives of rasagiline including propargylamine itself has shown that the above described pharmacological action of these compounds resides in the propargylamine moiety. These results have provided a new understanding into the mechanism of neuroprotective actions of rasagiline and its anti-Alzheimer drug derivatives TV3326 and TV3279, which are relevant for therapy of Parkinson's disease, Alzheimer's disease and other neurodegenerative diseases.

Contrasting Neuroprotective and Neurotoxic Actions of Respective Metabolites of Anti-Parkinson Drugs Rasagiline and Selegiline

Neuroscience Letters. Jan, 2004  |  Pubmed ID: 14732458

The anti-Parkinson selective irreversible monoamine oxidase B inhibitor drugs, rasagiline and selegiline, have been shown to possess neuroprotective activities in cell culture and in vivo models. While rasagiline is metabolized to its major metabolite aminoindan, selegiline gives rise to L-methamphetamine. Cultured PC-12 cells in absence of serum and nerve growth factor (NGF) die by an apoptotic process. Pretreatment of PC12 cells in absence of serum and NGF for 24 h with either rasagiline (1 microM) or selegiline (1 microM) is neuroprotective and anti-apoptotic as determined by ELISA and MTT tests. However, while aminoindan (1 microM), the major metabolite of rasagiline does not interfere with the neuroprotective activities of rasagiline or selegiline in PC-12 cells deprived of serum and NGF, the major metabolite of selegiline, L-methamphetamine (1 microM), inhibits them. In contrast to L-methamphetamine, aminoindan is itself is neuroprotective in this system. Recently it has been demonstrated that rasagiline directly activates PKC-MAP kinase pathway by a concentration and time dependent phosphorylation of p42 and p44 MAP kinase. In the present studies the neuroprotective activity of rasagiline is blocked by ERK inhibitor, PD98059 (20 microM), suggesting the involvement of PKC-MAP kinase pathway in the neuroprotection. These findings may have implication for the possible disease modifying action of rasagiline in treatment of Parkinson's disease.

Rasagiline: Neurodegeneration, Neuroprotection, and Mitochondrial Permeability Transition

Journal of Neuroscience Research. Jan 1-15, 2005  |  Pubmed ID: 15573406

Mitochondria are involved directly in cell survival and death. The assumption has been made that drugs that protect mitochondrial viability and prevent apoptotic cascade-induced mitochondrial permeability transition pore (MPTp) opening will be cytoprotective. Rasagiline (N-propargyl-1R-aminoindan) is a novel, highly potent irreversible monoamine oxidase (MAO) B inhibitor anti-Parkinson drug. Unlike selegiline, it is not derived from amphetamine, and is not metabolized to neurotoxic L-methamphetamine derivative. In addition, it does not have sympathomimetic activity. Rasagiline is effective as monotherapy or adjunct to levodopa for patients with early and late Parkinson's disease (PD) and adverse events do not occur with greater frequency in subjects receiving rasagiline than in those on placebo. Phase III controlled studies indicate that it might have a disease-modifying effect in PD that may be related to its neuroprotective activity. Its S isomer, TVP1022, is more than 1,000 times less potent as an MAO inhibitor. Both drugs, however, have neuroprotective activity in neuronal cell cultures in response to various neurotoxins, and in vivo in response to global ischemia, neurotrauma, head injury, anoxia, etc., indicating that MAO inhibition is not a prerequisite for neuroprotection. Their neuroprotective effect has been demonstrated to be associated directly with the propargylamine moiety, which protects mitochondrial viability and MTPp by activating Bcl-2 and protein kinase C (PKC) and by downregulating the proapoptotic FAS and Bax protein families. Rasagiline and its derivatives also process amyloid precursor protein (APP) to the neuroprotective, neurotrophic, soluble APP alpha (sAPPalpha) by PKC- and MAP kinase-dependent activation of alpha-secretase. The identification of the propargylamine moiety as the neuroprotective component of rasagiline has led us to development of novel bifunctional anti-Alzheimer drugs (ladostigil) possessing cholinesterase and brain-selective MAO inhibitory activity and a similar neuroprotective mechanism of action.

Novel Multifunctional Anti-Alzheimer Drugs with Various CNS Neurotransmitter Targets and Neuroprotective Moieties

Current Alzheimer Research. Dec, 2007  |  Pubmed ID: 18220515

Traditionally, drug design programs are focused on optimizing the specificity of lead compounds against a carefully selected drug target. Disappointingly, this approach to discover a "magic bullet" drug has not met with the expected success for CNS disorders. Transcriptomics and proteomic profiling of neurodegenerative diseases have indicated that they are poly-etiological in origin and that the processes leading to neuronal death are multifactorial. An emerging concept is the design of drug ligands that modulate multiple drug targets identified for a particular disease. In this review we explore some examples of multifunctional drugs which may be useful in the treatment of neurodegenerative diseases, such as Alzheimer's and Parkinson's disease.

The Inactivation of a New Peptidoglycan Hydrolase Pmp23 Leads to Abnormal Septum Formation in Streptococcus Pneumoniae

The Open Microbiology Journal. 2008  |  Pubmed ID: 19088920

The bacterial peptidoglycan is the major component of the cell wall which integrity is essential to cell survival. In a previous work, we identified, in the positive-Gram pathogen Streptococcus pneumoniae , a unique protein containing a new putative peptidoglycan hydrolytic domain named PECACE (PEptidoglycan CArbohydrate Cleavage Enzyme). In this study, we characterise the physiological function of this protein called Pmp23 (Pneumococcal Membrane Protein of 23 kDa). A cell wall hydrolytic activity is observed with the recombinant protein. Inactivation of the pmp23 gene in the pneumococcus led to a decreased flocculation, an increased sensitivity to beta-lactam antibiotics and morphological alterations affecting the formation and localisation of the division septa. Taken together these observations indicate that Pmp23 is a hydrolase whose function is linked to peptidoglycan metabolism at the septum site.

Gonadotrophin Releasing Hormone Antagonist in IVF/ICSI

Journal of Human Reproductive Sciences. Jan, 2008  |  Pubmed ID: 19562061

To study the efficacy of gonadotrophin releasing hormone (GnRH) antagonist in In-vitro-fertilization/Intracytoplasmic sperm injection (IVF/ICSI) cycles.

Trust in Nanotechnology? On Trust As Analytical Tool in Social Research on Emerging Technologies

Nanoethics. Apr, 2011  |  Pubmed ID: 21603037

Trust has become an important aspect of evaluating the relationship between lay public and technology implementation. Experiences have shown that a focus on trust provides a richer understanding of reasons for backlashes of technology in society than a mere focus of public understanding of risks and science communication. Therefore, trust is also widely used as a key concept for understanding and predicting trust or distrust in emerging technologies. But whereas trust broadens the scope for understanding established technologies with well-defined questions and controversies, it easily fails to do so with emerging technologies, where there are no shared questions, a lack of public familiarity with the technology in question, and a restricted understanding amongst social researchers as to where distrust is likely to arise and how and under which form the technology will actually be implemented. Rather contrary, 'trust' might sometimes even direct social research into fixed structures that makes it even more difficult for social research to provide socially robust knowledge. This article therefore suggests that if trust is to maintain its important role in evaluating emerging technologies, the approach has to be widened and initially focus not on people's motivations for trust, but rather the object of trust it self, as to predicting how and where distrust might appear, how the object is established as an object of trust, and how it is established in relation with the public.

Centre and Periphery of Nano-A Norwegian Context

Nanoethics. Apr, 2011  |  Pubmed ID: 21603038

This work describes the nano field in Norway as currently emerging in the dynamics between two forms of nano research activities described along a centre-periphery axis. 1) There are strategic research initiatives committed to redeem the envisioned potential of the field by means of social and material reorganisation of existing research activities. This activity is seen as central as it is one of our premises that the standard circulating nano vision implies such a work of reorganisation. The fact that nano is often taken as a paradigmatic example of the shift from Mode-1 to Mode-2 research, supports this assumption. 2) In parallel to this activity, a wide variety of research projects pursuing nano strategies are being funded. We regard such research activity as peripheral in so far as the activity is not marked by being committed to the circulating nano vision, as may often be the case. In the process of reorganising, this article argues, the research activity at the periphery provides a crucial arena for discussing and validating what is to be achieved through the work of reorganisation that takes place at the centre. Our analysis is informed by two Norwegian cases. We examine a major nano research initiative at a Norwegian university as a centre and a research project utilising nanoparticles in fish vaccines as a periphery.

Trust As Glue in Nanotechnology Governance Networks

Nanoethics. Apr, 2011  |  Pubmed ID: 21603041

This paper reflects on the change of relations among participants in nanotechnology governance through their participation in governance processes such as stakeholder dialogues. I show that policymaking in practice-that is, the practice of coming and working together in such stakeholder dialogues-has the potential for two-fold performative effects: it can contribute to the development of trust and mutual responsibility on the part of the involved actors, and it may bring about effects on the formation of boundaries of what is sayable and thinkable in nanotechnology governance. Three vignettes about the work of the German NanoKommission indicate the development of new relations of trust, recognition and mutual responsibility among actors. It is concluded that governance in practice can assemble new collectives in which relations of trust are the glue holding the complex structure together. While such a consensus-based progress may be favourable for smooth technology development, it can be considered problematic if evaluated against the ideals of deliberative democracy, which often form the premises on which public engagement is based. Stakeholder forums were set in place with the intention of including various actors, but this is Janus-faced: if a dialogue becomes encapsulated in new governance networks, new exclusions can arise. For example, a policing of which information is released to a wider audience can occur.

Epidemiological Risk Factors Associated with Inflammatory Breast Cancer Triple Negative Subtype

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. Feb, 2012  |  Pubmed ID: 22337546

BACKGROUND: Inflammatory breast cancer (IBC) is rare and accounts for ∼1% of all invasive breast cancers. The 5-year survival rates are significantly lower than for other types of breast cancer, highlighting the significance of cancer prevention in IBC. A disproportionately higher percentage of IBC patients have triple-negative breast cancer (TNBC; ER(-), PR(-) and Her2(-)) than patients with non-IBC. TNBCs are thought to arise from normal breast stem cells. Our preliminary data indicates that normal breast stem cells are enriched in adjacent normal tissues of patients with TN IBC. We hypothesize that parity and breastfeeding, risk factors that influence the normal stem cell compartment in the breast, will differ between TN IBC and non-TN IBC subtypes.METHODS: We identified 144 patients diagnosed with IBC in 1991-2011 at MD Anderson. Breast cancer risk factors including parity and breast-feeding were compared between patients with TN and non-TN IBC with chi square or Wilcoxon rank sum tests.RESULTS: The average age at diagnosis was 54 years; 83% of patients were non-Hispanic white; and 36% were TN IBC. We found that patients with TN IBC had significantly lower frequency (p = 0.02) and duration of breastfeeding (p = 0.02) compared with non-TN IBC patients. No differences were found in the frequency of other breast cancer risk factors.CONCLUSION: The association between breastfeeding and TNBC indicates that stem cells that are retained in the absence of breastfeeding may be the cell of origin for TN IBC. These results highlight the importance of evaluating epidemiologic risk factors of IBC according to receptor subtype, which could lead to the identification of distinct etiologic pathways that could be targeted for prevention. Cancer Epidemiol Biomarkers Prev; 21(3); 1-9. ©2012 AACR.