Federal food, drug, and cosmetic act, a statement of its legislative record /

Mode of access: Internet.

Federal food, drug, and cosmetic act, a statement of its legislative record,

Mode of access: Internet.

Illinois' multiyear strategy to control drug and violent crime, FFY 2004.

In June 2000, the Authority convened a Criminal Justice Planning Assembly in which policy makers, service providers, researchers, practitioners, and elected officials participated. The goals and objectives for the criminal justice system, which came out of the Assembly, were refined in the following months and recommended action steps to address identified priorities were developed. This work resulted in a Criminal Justice Plan for the State of Illinois. A primary purpose of the Plan was the development of a framework for a comprehensive statewide approach to coordinating the allocation and expenditure of all federal and state funds appropriated to the Authority and made available for juvenile and criminal justice purposes. The Plan as well as past funding initiatives, the latest data on drug and violent crime in Illinois, and new criminal justice issues that have arisen in the last several years were taken into account in the development of the strategy. The strategy describes the role that Illinois' Anti-Drug Abuse Act Edward Byrne Memorial Fund award plays in the larger plan for Illinois, coordinating research, policy, and the legislative activities with funding initiatives.

Oil, paint and drug reporter.

Vols. include the proceedings (some summarized, some official stenographic reports) of the National Wholesale Druggists' Association (called 18 -1882, Western Wholesale Druggists' Association) and of other similar organizations.

Drug and chemical markets.

Mode of access: Internet.

Ionic interpretation of drug action in chemotherapeutic research.

Mode of access: Internet.

Difficult macrocyclizations: New strategies for synthesizing highly strained cyclic tetrapeptides

Cyclic tetrapeptides are an intriguing class of natural products. To synthesize highly strained cyclic tetrapeptides; we developed a macrocyclization strategy that involves the inclusion of 2-hydroxy-6-nitrobenzyl (HnB) group at the N-terminus and in the middle of the sequence. The N-terminal auxiliary performs a ring closure/ring contraction role, and the backbone auxiliary promotes cis amide bonds to facilitate the otherwise difficult ring contraction. Following this route, the all-L cyclic tetrapeptide cyclo-[Tyr-Arg-Phe-Ala] was successfully prepared.

A new principle for tight junction modulation based on occludin peptides

The aim of this study was to investigate whether peptides from the extracellular loops of the tight junction protein occludin could be used as a new principle for tight junction modulation. Peptides of 4 to 47 amino acids in length and covering the two extracellular loops of the tight junction protein occludin were synthesized, and their effect on the tight junction permeability in Caco-2 cells was investigated using [C-14] mannitol as a paracellular marker. Lipopeptide derivatives of one of the active occludin peptides (OPs), synthesized by adding a lipoamino acid containing 14 carbon atoms (C-14-) to the N terminus of the peptide, were also investigated. Peptides corresponding to the N terminus of the first extracellular loop of occludin increased the permeability of the tight junctions without causing short-term toxicity. However, the peptides had an effect only when added to the basolateral side of the cells, which could be partly explained by degradation by apical peptidases and aggregate formation. By contrast, the lipopeptide C-14-OP90-103, which protects the peptide from degradation and aggregation, displayed a rapid apical effect. The L- and D-diastereomers of C-14-OP90-103 had distinctly different effects. The D-isomer, which releases intact OP90-103 from the lipoamino acid, displayed a rapid and transient increase in tight junction permeability. The L- isomer, which releases OP90-103 more rapidly, gave a more sustained increase in tight junction permeability. In conclusion, C-14-OP90-103 represents a prototype of a new class of tight junction modulators that act on the extracellular domains of tight junction proteins.

Effects of reduction in heroin supply on injecting drug use: analysis of data from needle and syringe programmes

n early 2001 there was a dramatic decline in the availability of heroin in New South Wales (NSW), Australia, where previously heroin had been readily available at a low price and high purity.1 The decline was confirmed by Australia's strategic early warning system, which revealed a reduction in heroin supply across Australia and a considerable increase in price,2 particularly from January to April 2001. This "heroin shortage" provided a natural experiment in which to examine the effect of substantial changes in price and availability on injecting drug use and its associated harms in Australia's largest heroin market,2 a setting in which harm reduction strategies were widely used. Publicly funded needle and syringe programmes were introduced to Australia in 1987, and methadone maintenance programmes, which were established in the 1970s, were significantly expanded in 1985 and again in 1999.

The impact of changes to heroin supply on blood-borne virus notifications and injecting related harms in New South Wales, Australia

Background: In early 2001 Australia experienced a sudden and unexpected disruption to heroin availability, know as the 'heroin shortage'. This 'shortage has been linked to a decrease in needle and syringe output and therefore possibly a reduction in injecting drug use. We aimed to examine changes, if any, in blood-borne viral infections and presentations for injecting related problems related to injecting drug use following the reduction heroin availability in Australia, in the context of widespread harm reduction measures. Methods: Time series analysis of State level databases on HIV, hepatitis B, hepatitis C notifications and hospital and emergency department data. Examination of changes in HIV, hepatitis B, hepatitis C notifications and hospital and emergency department admissions for injection-related problems following the onset of the heroin shortage; non-parametric curve-fitting of number of hepatitis C notifications among those aged 15 - 19 years. Results: There were no changes observed in hospital visits for injection-related problems. There was no change related to the onset heroin shortage in the number of hepatitis C notifications among persons aged 15 - 19 years, but HCV notifications have subsequently decreased in this group. No change occurred in HIV and hepatitis B notifications. Conclusion: A marked reduction in heroin supply resulted in no increase in injection-related harm at the community level. However, a delayed decrease in HCV notifications among young people may be related. These changes occurred in a setting with widespread, publicly funded harm reduction initiatives.

The impact of a reduction in drug supply on demand for and compliance with treatment for drug dependence

Background: In early 2001, Australia experienced a sudden, dramatic and;sustained decrease in heroin availability that was accompanied by sharp increases in price and decreases in street level purity-the so-called heroin shortage. These unprecedented changes occurred in a context of widespread treatment availability, which made it possible for the first time to examine the impact of a sharp reduction in heroin supply in New South Wales (NSW) on entry to and adherence with treatment for heroin dependence. Given the evidence of drug substitution by some users. the current paper also examines the effects of the shortage on entry to treatment for other forms of drug dependence. Methods: Interrupted time-series analysis of the number of persons entering opioid pharmacotherapy and other treatment modalities in NSW for heroin dependence and for the treatment for other types of drug dependence. Findings: The heroin shortage was associated with a reduction in the number of younger persons entering opioid pharmacotherapy. There was a dramatic decrease in the number of persons entering heroin withdrawal or assessment only treatment episodes. There appear to have been small improvements in adherence to and retention in heroin treatment after the reduction in heroin supply. Relatively small increases were observed in numbers being treated for cocaine dependence. Conclusions: In the context of good treatment provision, a reduction in heroin supply appeared to produce modest improvements in intermediate outcomes. Supply and demand reduction measures, when both are implemented successfully, may be complementary. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Structure-activity relationships for a new family of sulfonylurea herbicides

Acetohydroxyacid synthase (AHAS; EC 2.2.1.6) catalyzes the first common step in branched-chain amino acid biosynthesis. The enzyme is inhibited by several chemical classes of compounds and this inhibition is the basis of action of the sulfonylurea and imidazolinone herbicides. The commercial sulfonylureas contain a pyrimidine or a triazine ring that is substituted at both meta positions, thus obeying the initial rules proposed by Levitt. Here we assess the activity of 69 monosubstituted sulfonylurea analogs and related compounds as inhibitors of pure recombinant Arabidopsis thaliana AHAS and show that disubstitution is not absolutely essential as exemplified by our novel herbicide, monosulfuron (2-nitro-N-(4'-methyl-pyrimidin-2'-yl) phenyl-sulfonylurea), which has a pyrimidine ring with a single meta substituent. A subset of these compounds was tested for herbicidal activity and it was shown that their effect in vivo correlates well with their potency in vitro as AHAS inhibitors. Three-dimensional quantitative structure-activity relationships were developed using comparative molecular field analysis and comparative molecular similarity indices analysis. For the latter, the best result was obtained when steric, electrostatic, hydrophobic and H-bond acceptor factors were taken into consideration. The resulting fields were mapped on to the published crystal structure of the yeast enzyme and it was shown that the steric and hydrophobic fields are in good agreement with sulfonylurea-AHAS interaction geometry.

Field evaluation of anthelmintic drug sensitivity using in vitro egg hatch and larval motility assays with Necator americanus recovered from human clinical isolates

A field-applicable assay for testing anthelmintic sensitivity is required to monitor for anthelmintic resistance. We undertook a study to evaluate the ability of three in vitro assay systems to define drug sensitivity of clinical isolates of the human hookworm parasite Necator americanus recovered from children resident in a village in Madang Province, Papua New Guinea. The assays entailed observation of drug effects on egg hatch (EHA), larval development (LDA), and motility of infective stage larvae (LMA). The egg hatch assay proved the best method for assessing the response to benzimidazole anthelmintics, while the larval motility assay was suitable for assessing the response to ivermectin. The performance of the larval development assay was unsatisfactory on account of interference caused by contaminating bacteria. A simple protocol was developed whereby stool samples were subdivided and used for immediate egg recovery, as well as for faecal culture, in order to provide eggs and infective larvae, respectively, for use in the egg hatch assay and larval motility assay systems. While the assays proved effective in quantifying drug sensitivity in larvae of the drug-susceptible hookworms examined in this study, their ability to indicate drug resistance in larval or adult hookworms remains to be determined. (c) 2005 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Documenting the heroin shortage in New South Wales

Australian heroin markets have recently undergone dramatic change, sparking debate about the nature of such markets. This study aimed to determine the onset, peak and decline of the heroin shortage in New South Wales (NSW), using the most appropriate available methods to detect market level changes. The parameters of the heroin shortage were determined by reviewing: reports of heroin users about availability and price (derived from the existing literature and the Illicit Drug Reporting System); qualitative interviews with injecting drug users, and health and law enforcement professionals working in the illicit drug field; and examining data on heroin seizures over the past decade. There was a marked reduction in heroin supply in NSW in early 2001. An increase in the price of heroin occurred in 2001, whereas it had decreased steadily since 1996. A reduction in purity also occurred, as reported by drug users and heroin seizures. The peak period of the shortage appears to have been January to April 2001. The market appears to have stabilised since that time, although it has not returned to pre- 2001 levels: heroin prices have decreased in NSW for street grams, but not to former levels, and the price of `caps' (street deals) remain elevated. Heroin purity in NSW has remained low, with perhaps a 10% increase above the lowest recorded levels. These data support the notion that the heroin market in NSW underwent significant changes, which appear to have involved a lasting shift in the nature of the market.