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Biomedical subjects

R Hardy

Publications and source records attributed to R Hardy.

At least 127 records · Page 7Linked to original sources

Some oxidation products of ethoxyquin including those found in autoxidising systems.

2,4-Dimethyl-6-ethoxyquinoline (2), 1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline nitroxide (3), 2,6-dihydro-2,2,4-trimethyl-6-quinone imine N-oxide (4), 2,6-dihydro-2,2,4-trimethyl-6-quinone imine (5), 1.8' -di(1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline) (6) and 1,2-dihydro-6-hydroxy-2,2,4-trimethylquinoline (7) have been prepared from 1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline (1) (ethoxyquin) and their spectroscopic properties (UV, IR, mass and NMR) examined.

Carbon Isotopes↗

Correlation between segmental flexibility and effector function of antibodies.

Mouse monoclonal anti-dansyl antibodies with the same antigen-binding sites but different heavy chain constant regions were generated. The extent of segmental flexibility in times of nanoseconds and the capacity to fix complement were greatest for IgG2b, intermediate for IgG2a, and least for IgG1 and IgE. Hence, the effector functions of immunoglobulin isotypes may be controlled in part by the freedom of movement of their Fab arms.

Animals↗

Development of a method for the determination of oxytetracycline in trout.

An HPLC method has been developed whereby oxytetracycline can be detected in trout muscle at 0.005 mg kg-1. Application of the method to retail samples has shown that a few contained the antibiotic. The amounts found ranged from 0.008-0.037 mg kg-1, these concentrations being considerably below that specified under the Medicine Act review procedures.

Animals↗

The importance of endogenous histamine relative to dietary histamine in the aetiology of scombrotoxicosis.

Deliberately spoiled mackerel samples and mackerel samples implicated in outbreaks of scombrotoxicosis were, under medical supervision, tested blind on normal, healthy volunteers of both sexes. These experiments identified batches of fish which could induce nausea/vomiting and/or diarrhoea when 50 g samples were consumed. It was also established that the fillets in a batch were neither of equal potency nor homogeneous with respect to histamine content. Strong evidence was obtained that dietary histamine is not a major determinant of scombrotoxicosis since potency was not positively correlated with the dose, and volunteers appeared to fall into susceptible and non-susceptible subgroups. However, there is no reason to suspect allergy as being solely responsible for these differences in sensitivity. It is also possible to discount body weight as a factor. While the data suggest that females may be more susceptible than males, this effect cannot be confirmed at the present time. Studies with susceptible volunteers predosed with either placebo or H1 antagonist (chlorpheniramine 4 mg) demonstrated convincingly that the antihistamine can abolish vomiting and diarrhoea associated with the ingestion of 50 g of scombrotoxic fish. It is therefore postulated that endogenous histamine released by mast cell degranulation has a significant role in the aetiology of scombrotoxicosis, whereas the role of dietary histamine is minor. The nature and origin of the agent responsible for mast cell degranulation is being investigated.

Chlorpheniramine↗

Is there a role for amines other than histamines in the aetiology of scombrotoxicosis?

Mackerel fillets associated with an outbreak of scombrotoxicosis have been analysed for their contents of cadaverine, histamine, putrescine, spermidine, spermine and tyramine, and fed to informed, healthy volunteers of both sexes under medical supervision. Of the 86 fillets examined, 30 rapidly induced nausea/vomiting and/or diarrhoea when 50 g were consumed. The remaining fillets failed to provoke such symptoms, even though 17 of them were tested by volunteers proven to be susceptible to scombro-intoxication. Statistical analysis failed to detect any differences in amines content between fillets shown to be scombrotoxic and those failing to induce nausea/vomiting and/or diarrhoea, and failed also to establish any significant relationships between the amines doses and volunteer responses, even after manipulations to simulate additive or synergistic interactions. Accordingly it is concluded that the content of such amines in mackerel have little or no role in the aetiology of scombrotoxicosis.

Amines↗

Do saxitoxin-like substances have a role in scombrotoxicosis?

Evidence is presented which establishes that mackerel fed in captivity can, by relay from contaminated shellfish via sand eels, accumulate paralytic shellfish poisons (PSP) in the edible flesh at a level (250 micrograms saxitoxin equivalents per kg) similar to that in the contaminated shellfish. Data from ELISAs performed independently in two laboratories show that commercial mackerel fillets which have been associated with incidents of scombrotoxicosis contained 0.02-1.30 micrograms saxitoxin equivalents per kg, concentrations some two to four orders of magnitude below that normally detectable by the mouse bioassay. The doses, expressed as saxitoxin equivalents, administered inadvertently during volunteer testing of such fillets ranged up to 0.5 ng/kg bw, at least four orders of magnitude less than the fatal oral dose for an adult. The doses associated with the rapid induction of nausea/vomiting and/or diarrhoea, 0.11-1.0 ng/kg bw, could not be distinguished from the doses which failed to produce such symptoms in susceptible volunteers (up to 0.5 ng/kg bw). Factors that might explain this lack of correlation between dose (saxitoxin equivalents) and volunteer response are discussed along with previously published reports of PSP relay through the food web. It is suggested that the relay of algal toxins, particularly PSP, but possibly in combination with diarrheic shellfish poisons, may be responsible for scombrotoxicosis.

Animals↗