The ophthalmic and intradermic tests for glanders /

Mode of access: Internet.

A source-book of biological names and terms.

Mode of access: Internet.

Chemosterilants screened against the boll weevil in dipping and feeding tests /

"In cooperation with Mississippi Agricultural Experiment Station."

Biological warfare and terrorism : the military and public health response : student material /

"Satellite broadcast, September 21-23, 1999."

Roles of transmembrane domain 2 and the first intracellular loop in human noradrenaline transporter function: pharmacological and SCAM analysis

The aim was to investigate the roles of transmembrane domain 2 and the adjacent region of the first intracellular loop in determining human noradrenaline transporter (hNET) function by pharmacological and substituted-cysteine accessibility method (SCAM) analyses. It was first necessary to establish a suitable background NET for SCAM. Alanine mutants of endogenous hNET cysteines, hC86A, hC131A and hC339A, were examined and showed no marked effects on expression or function. hNET and the mutants were also resistant to methanethiosulfonate (MTS), ethylammonium (MTSEA) and MTStrimethylammonium (MTSET). Hence, wild-type hNET is an appropriate background for production of cysteine mutants for SCAM. Pharmacological investigation showed that all mutants except hT99C and hL109C showed reduced cell-surface expression, while all except hM107C showed a reduction in functional activity. The mutations did not markedly affect the apparent affinities of substrates, but apparent affinities of cocaine were decreased 7-fold for hP97C and 10-fold for hF101C and increased 12-fold for hY98C. [H-3]Nisoxetine binding affinities were decreased 13-fold for hP97C and 5-fold for hF101C. SCAM analysis revealed that only hL102C was sensitive to 1.25 mM MTSEA, and this sensitivity was protected by noradrenaline, nisoxetine and cocaine. The results suggest that this region of hNET is important for interactions with antidepressants and cocaine, but it is probably not involved in substrate translocation mechanisms.

Synthesis, biological activity, and preliminary pharmacokinetic evaluation of analogues of a phosphosulfomannan angiogenesis inhibitor (PI-88)

The phosphosulfomannan 1 (PI-88) is a mixture of highly sulfated oligosaccharides that is currently undergoing clinical evaluation in cancer patients. As well as it's anticancer properties, 1 displays a number of other interesting biological activities. A series of analogues of 1 were synthesized with a single carbon (pentasaccharide) backbone to facilitate structural characterization and interpretation of biological results. In a fashion similar to 1, all compounds were able to inhibit heparanase and to bind tightly to the proangiogenic growth factors FGF-1, FGF-2, and VEGF. The compounds also inhibited the infection of cells and cell-to-cell spread of herpes simplex virus (HSV-1). Preliminary pharmacokinetic data indicated that the compounds displayed different pharmacokinetic behavior compared with 1. Of particular note was the n-octyl derivative, which was cleared 3 times less rapidly than 1 and may provide increased systemic exposure.

Biological monitoring and Biological Limit Values (BLV): The strategy of the European Union

Occupational standards concerning allowable concentrations of chemical compounds in the ambient air of workplaces have been established in several countries worldwide. With the integration of the European Union (EU), there has been a need of establishing harmonised Occupational Exposure Limits (OEL). The European Commission Directive 95/320/EC of 12 July 1995 has given the tasks to a Scientific Committee for Occupational Exposure Limits (SCOEL) to propose, based on scientific data and where appropriate, occupational limit values which may include the 8-h time-weighted average (TWA), short-term limits/excursion limits (STEL) and Biological Limit Values (BLVs). In 2000, the European Union issued a list of 62 chemical substances with Occupational Exposure Limits. Of these, 25 substances received a skin notation, indicating that toxicologically significant amounts may be taken up via the skin. For such substances, monitoring of concentrations in ambient air may not be sufficient, and biological monitoring strategies appear of potential importance in the medical surveillance of exposed workers. Recent progress has been made with respect to formulation of a strategy related to health-based BLVs. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Biological, antigenic and phylogenetic characterization of the flavivirus Alfuy

Alfuy virus (ALFV) is classified as a subtype of the flavivirus Murray Valley encephalitis virus (MVEV); however, despite preliminary reports of antigenic and ecological similarities with MVEV, ALFV has not been associated with human disease. Here, it was shown that ALFV is at least 10(4)-fold less neuroinvasive than MVEV after peripheral inoculation of 3-week-old Swiss outbred mice, but ALFV demonstrates similar neurovirulence. In addition, it was shown that ALFV is partially attenuated in mice that are deficient in alpha/beta interferon responses, in contrast to MVEV which is uniformly lethal in these mice. To assess the antigenic relationship between these viruses, a panel of monoclonal antibodies was tested for the ability to bind to ALFV and MVEV in ELISA. Although the majority of monoclonal antibodies recognized both viruses, confirming their antigenic similarity, several discriminating antibodies were identified. Finally, the entire genome of the prototype strain of ALFV (MRM3929) was sequenced and phylogenetically analysed. Nucleotide (73%) and amino acid sequence (83 %) identity between ALFV and IMVEV confirmed previous reports of their close relationship. Several nucleotide and amino acid deletions and/or substitutions with putative functional significance were identified in ALFV, including the abolition of a conserved glycosylation site in the envelope protein and the deletion of the terminal dinucleotide 5'-CUOH-3' found in all other members of the genus. These findings confirm previous reports that ALFV is closely related to IMVEV, but also highlights significant antigenic, genetic and phenotypic divergence from MVEV. Accordingly, the data suggest that ALFV is a distinct species within the serogroup Japanese encephalitis virus.

Structural plasticity of the cyclic-cystine-knot framework: implications for biological activity and drug design

The cyclotide family of plant proteins is of interest because of their unique topology, which combines a head-to-tail cyclic backbone with an embedded cystine knot, and because their-remarkable chemical and biological properties make them ideal candidates as grafting templates for biologically active peptide epitopes. The present Study describes the first steps towards exploiting the cyclotide framework by synthesizing and structurally characterizing two grafted analogues of the cyclotide kalata B1. The modified peptides have polar or charged residues substituted for residues that form part of a surface-exposed hydrophobic patch that plays a significant role in the folding and biological activity of kalata B1. Both analogues retain the native cyclotide fold, but lack the undesired haemolytic activity of their parent molecule, kalata B1. This finding confirms the tolerance of the cyclotide framework to residue Substitutions and opens up possibilities for the Substitution of biologically active peptide epitopes into the framework.

A review of non-pharmacological and pharmacological management of seasonal and perennial allergic conjunctivitis

Allergic eye disease encompasses a group of hypersensitivity disorders which primarily affect the conjunctiva and its prevalence is increasing. It is estimated to affect 8% of patients attending optometric practice but is poorly managed and rarely involves ophthalmic assessment. Seasonal allergic conjunctivitis (SAC) is the most common form of allergic eye disease (90%), followed by perennial allergic conjunctivitis (PAC; 5%). Both are type 1 IgE mediated hypersensitivity reactions where mast cells play an important role in pathophysiology. The signs and symptoms are similar but SAC occurs periodically whereas PAC occurs year round. Despite being a relatively mild condition, the effects on the quality of life can be profound and therefore they demand attention. Primary management of SAC and PAC involves avoidance strategies depending on the responsible allergen(s) to prevent the hypersensitivity reaction. Cooled tear supplements and cold compresses may help bring relief. Pharmacological agents may become necessary as it is not possible to completely avoid the allergen(s). There are a wide range of anti-allergic medications available, such as mast cell stabilisers, antihistamines and dual-action agents. Severe cases refractory to conventional treatment require anti-inflammatories, immunomodulators or immunotherapy. Additional qualifications are required to gain access to these medications, but entry-level optometrists must offer advice and supportive therapy. Based on current evidence, the efficacy of anti-allergic medications appears equivocal so prescribing should relate to patient preference, dosing and cost. More studies with standardised methodologies are necessary elicit the most effective anti-allergic medications but those with dual-actions are likely to be first line agents.

Use of complementary and alternative medicine and self-tests by coronary heart disease patients

Background: Coronary heart disease patients have to learn to manage their condition to maximise quality of life and prevent recurrence or deterioration. They may develop their own informal methods of self-management in addition to the advice they receive as part of formal cardiac rehabilitation programmes. This study aimed to explore the use of complementary and alternative medicines and therapies (CAM), self-test kits and attitudes towards health of UK patients one year after referral to cardiac rehabilitation. Method: Questionnaire given to 463 patients attending an assessment clinic for 12 month follow up in four West Midlands hospitals. Results: 91.1% completed a questionnaire. 29.1% of patients used CAM and/or self-test kits for self-management but few (8.9%) used both methods. CAM was more often used for treating other illnesses than for CHD management. Self-test kit use (77.2%,) was more common than CAM (31.7%,) with BP monitors being the most prevalent (80.0%). Patients obtained self-test kits from a wide range of sources, for the most part (89.5%) purchased entirely on their own initiative. Predictors of self-management were post revascularisation status and higher scores on 'holism', 'rejection of authority' and 'individual responsibility'. Predictors of self-test kit use were higher `holism' and 'individual responsibility' scores. Conclusion: Patients are independently using new technologies to monitor their cardiovascular health, a role formerly carried out only by healthcare practitioners. Post-rehabilitation patients reported using CAM for self-management less frequently than they reported using self-test kits. Reports of CAM use were less frequent than in previous surveys of similar patient groups. Automatic assumptions cannot be made by clinicians about which CHD patients are most likely to self-manage. In order to increase trust and compliance it is important for doctors to encourage all CHD patients to disclose their self-management practices and to continue to address this in follow up consultations.