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Biomedical subjects

N Gray

Publications and source records attributed to N Gray.

At least 19 recordsLinked to original sources
PubMed2005

Toward a comprehensive long term nicotine policy.

Global tobacco deaths are high and rising. Tobacco use is primarily driven by nicotine addiction. Overall tobacco control policy is relatively well agreed upon but a long term nicotine policy has been less well considered and requires further debate. Reaching consensus is important because a nicotine policy is integral to the target of reducing tobacco caused disease, and the contentious issues need to be resolved before the necessary political changes can be sought. A long term and comprehensive nicotine policy is proposed here. It envisages both reducing the attractiveness and addictiveness of existing tobacco based nicotine delivery systems as well as providing alternative sources of acceptable clean nicotine as competition for tobacco. Clean nicotine is defined as nicotine free enough of tobacco toxicants to pass regulatory approval. A three phase policy is proposed. The initial phase requires regulatory capture of cigarette and smoke constituents liberalising the market for clean nicotine; regulating all nicotine sources from the same agency; and research into nicotine absorption and the role of tobacco additives in this process. The second phase anticipates clean nicotine overtaking tobacco as the primary source of the drug (facilitated by use of regulatory and taxation measures); simplification of tobacco products by limitation of additives which make tobacco attractive and easier to smoke (but tobacco would still be able to provide a satisfying dose of nicotine). The third phase includes a progressive reduction in the nicotine content of cigarettes, with clean nicotine freely available to take the place of tobacco as society's main nicotine source.

Health Policy↗
PubMed2004

The impact of sludge amendment on gas dynamics in an upland soil: monitored by membrane inlet mass spectrometry.

Studies of the land disposal of biosolids and municipal sewage have focused largely on the potential pollution of the soil with pathogens, toxic compounds or heavy metals. Little is known about the impact of sludge amendment on carbon source and sink concentrations in soils. In this study gas concentrations in Scottish soil cores (from limed and unlimed plots) were monitored continuously at 3 cm depth before, during and after sludge application using membrane inlet mass spectrometry (MIMS). Following sludge application to soil cores, significant and sustained increases in CH4 (for 8 days) and CO2 (for between 16 and 120 days) concentration were observed. This suggested short-term stimulation of indigenous methanogens, provision of a new methanogenic inoculum, or inhibition of methane oxidizers (for example by heavy metals or NH4 in sludge). Soil microbial fermentative activity was enhanced over periods of a few months as shown by elevated CO2 concentrations.

Bacteria↗
PubMed2004

The case of the disappearing nitrosamines: a potentially global phenomenon.

The cigarette usually carries in its smoke significant doses of carcinogenic tobacco specific nitrosamines (TSNAs), which have been implicated as causes of oral, lung, oesophageal, and pancreatic cancer. However, there is substantial variation in nitrosamine content of the smoke of modern cigarettes. This variation is both unacceptable and unnecessary, as TSNAs can be readily removed during the manufacturing process. Removing a known carcinogen needs no justification, even though proof of benefit may not be forthcoming for decades.

Carcinogens↗
PubMed2004

Creating chemical diversity to target protein kinases.

Protein kinases play crucial roles in regulating virtually every cellular process and are currently attracting tremendous interest as drug targets from the pharmaceutical industry. The major challenges facing the development of the potential kinase inhibitor drugs are: selectivity, physical properties (solubility, molecular weight), and pharmacological properties (bioavailability, half life, toxicity, etc.) This review focuses on how selective protein kinase inhibitors that target the ATP and allosteric binding sites are currently being identified and optimized.

Animals↗
PubMed2003

More on the regulation of tobacco smoke: how we got here and where next.

The modern cigarette is unnecessarily dangerous. Despite being lower in tar yield, and consequently in squamo-carcinogenic polyaromatic hydrocarbons such as benzo[a]pyrene, the nitrosamine yields are often higher than they need to be. Also, reductions in tar levels have not led to the consequential reductions in mortality that were anticipated several decades ago. The modern cigarette is also smoother, easier to smoke and to learn how to smoke, highly addictive and facilitates compensatory smoking. Compensatory smoking leads to excess inhalation of carcinogens and toxins in the hunt for nicotine. Its labelling is misleading in that supposedly low-yielding cigarettes may, due to compensation occurring as a result of cigarette design, lead to inhalation of much higher amounts of nicotine, carcinogens and toxins than the smoker is led to expect. Regulation of the product is needed to provide the persistent smoker with a cigarette lower in risk, accurately labelled, providing a relatively consistent and known dose of nicotine, and less likely to facilitate compensatory smoking. This will not produce a safe cigarette but should result in a reduction in harm if seriously implemented.

Carcinogens↗
PubMed2003

The Australian tar derby: the origins and fate of a low tar harm reduction programme.

OBJECTIVE: To document the development of the low tar harm reduction programme in Australia, including tobacco industry responses. DATA SOURCES: Tobacco industry documents, retail tobacco journals, newspapers, medical journals, and Anti-Cancer Council of Victoria (ACCV) newsletters and archival records. STUDY SELECTION: Documents on the strategies and knowledge bases of the ACCV, other Australian health authorities, and the tobacco industry. RESULTS: The ACCV built a durable system for measuring and publicising the tar and nicotine yields of Australian cigarettes and influencing their development. The tobacco industry initially sought to block the development of this system but later appeared to cooperate with it, as is evidenced by the current market dominance of low tar brands. However, behind the scenes, the industry used its substantial knowledge advantage regarding compensatory smoking and its ability to re-engineer cigarettes to gain effective control of the system and subvert the ACCV's objectives. CONCLUSIONS: Replacement of the low tar programme with new means of minimising the harms from cigarette smoking should be a policy priority for the Australian government. This will require regulation, rather than further voluntary agreements, and stringent monitoring of successor programmes will be necessary.

Australia↗
PubMed2003

A comparitive study of ammonia-oxidizing bacteria in lab-scale industrial wastewater treatment reactors.

The diversity and community structure of the beta-proteobacterial ammonia oxidising bacteria (AOB) in a range of different lab-scale industrial wastewater treatment reactors were compared. Three of the reactors treat waste from mixed domestic and industrial sources whereas the other reactor treats waste solely of industrial origin. PCR with AOB selective primers was combined with denaturing gradient ge electrophoresis to allow comparative analysis of the dominant AOB populations and the phylogenetic affiliation of the dominant AOB was determined by cloning and sequencing or direct sequencing of bands excised from DGGE gels. Different AOB were found within and between different reactors. All AOB sequences identified were grouped within the genus Nitrosomonas. Within the lab-scale reactors there appeared to be selection for a low diversity of AOB and predominance of a single AOB population. Furthermore, the industrial input in both effluents apparently selected for salt tolerant AOB, most closely related to Nitrosococcus mobilis and Nitrosomonas halophila.

Ammonia↗
PubMed2001

Structure-activity relationships and inhibitory effects of various purine derivatives on the in vitro growth of Plasmodium falciparum.

The development of novel chemotherapeutic agents has become an urgent task due to the development and rapid spread of drug resistance in Plasmodium falciparum, the protozoan parasite responsible for cerebral malaria. Cyclin-dependent kinases (CDKs) are essential for the regulation of the eukaryotic cell cycle, and several enzymes of this family have been identified in P. falciparum. In recent years, a number of purine-derived kinase inhibitors have been synthesised, some of which display selective activity against CDKs. This report describes a study in which various purine derivatives were screened for in vitro antimalarial activity. The erythrocytic asexual stages of the chloroquine-resistant P. falciparum strain (FCR-3) were cultivated in vitro in the presence of the various purines, and their effect on parasite proliferation was determined by the [3H]hypoxanthine incorporation assay. Our results show considerable variation in the sensitivity of P. falciparum to the different purines, as well as a general independence from their effect on purified starfish CDK1/cyclin B activity, which has been the standard assay used to identify CDK-specific inhibitors. Two subfamilies of purines with moderate to poor activity against CDK1/cyclin B activity showed submicromolar activity against P. falciparum. Structure-activity analysis indicates that certain structural features are associated with increased activity against P. falciparum. These features can be exploited to synthesise compounds with higher activity and specificity towards P. falciparum.

Adenine↗
PubMed2001

American Indian and Alaska Native substance abuse: co-morbidity and cultural issues.

The devastating impact of substance abuse on American Indians and Alaska Natives (AI/ANs) is reviewed with an emphasis on psychological and physical effects. Co-morbidity of substance abuse, trans-generational trauma, Post Traumatic Stress Disorder, and depression among AI/ANs is also discussed since each condition may cause, impact, and/or exacerbate the others. The Medicine Wheel, one respected and accepted treatment approach developed by AI/AN communities, is described in detail since it helps address all of the co-morbid issues discussed.

Adolescent↗
PubMed2000

Case reports of olanzapine treatment of anorexia nervosa.

Two females with severe anorexia nervosa were treated with olanzapine in open trials. Olanzapine was tried because it has caused weight gain in other patient groups. Both anorexic patients had a chronic illness and had failed multiple other treatments. Olanzapine administration was associated with weight gain and maintenance as well as reduced agitation and resistance to treatment. These case histories support further exploration of this class of drugs in anorexia nervosa.

Adolescent↗
PubMed2000

Intracellular targets of cyclin-dependent kinase inhibitors: identification by affinity chromatography using immobilised inhibitors.

BACKGROUND: Chemical inhibitors of cyclin-dependent kinases (CDKs) have great therapeutic potential against various proliferative and neurodegenerative disorders. Olomoucine, a 2,6,9-trisubstituted purine, has been optimized for activity against CDK1/cyclin B by combinatorial and medicinal chemistry efforts to yield the purvalanol inhibitors. Although many studies support the action of purvalanols against CDKs, the actual intracellular targets of 2,6, 9-trisubstituted purines remain unverified. RESULTS: To address this issue, purvalanol B (95. ) and an N6-methylated, CDK-inactive derivative (95M. ) were immobilized on an agarose matrix. Extracts from a diverse collection of cell types and organisms were screened for proteins binding purvalanol B. In addition to validating CDKs as intracellular targets, a variety of unexpected protein kinases were recovered from the 95. matrix. Casein kinase 1 (CK1) was identified as a principal 95. matrix binding protein in Plasmodium falciparum, Leishmania mexicana, Toxoplasma gondii and Trypanosoma cruzi. Purvalanol compounds also inhibit the proliferation of these parasites, suggesting that CK1 is a valuable target for further screening with 2,6,9-trisubstituted purine libraries. CONCLUSIONS: That a simple batchwise affinity chromatography approach using two purine derivatives facilitated isolation of a small set of highly purified kinases suggests that this could be a general method for identifying intracellular targets relevant to a particular class of ligands. This method allows a close correlation to be established between the pattern of proteins bound to a small family of related compounds and the pattern of cellular responses to these compounds.

Amino Acid Sequence↗