Studies with guinea-pigs

DIETARY FLAVONOIDS AND TISSUE ASCORBIC ACID Studies with guinea-pigs 

the elevation of tissue ascorbic acid is most readily demonstrated when the ascorbic acid intake is marginal reports of an effect in ascorbic acid-sufficient animals are rare  

the flavonoid-induced elevation of tissue ascorbic acid is most marked in, and is sometimes limited to, the adrenal glands. 

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Chamomile tea produced from the flowers of Matricaria, recutita has long been used as an antispasmodic for gastric and menstrual cramps. Studies with guinea-pig ileum have shown that the water-soluble flavonoid fraction and especially apigenin has antispasmodic activity three times that of papaverine. 

Interactions of ascorbic acid with folic acid have also been observed. Studies with guinea pigs have shown that folic acid deficiency is related to decreased concentrations of ascorbic acid in liver and adrenals (Lewis et ai, 1982). 

The dermal adsorption of DEBT in humans has been studied in the Netherlands by appHcation of DEBT as undiluted technical material or as 15% solutions in alcohol. Labeled material was recovered from the skin, and absorption of DEBT was indicated by the appearance of label in urine after two hours of skin exposure. About 5—8% of the appHed treatments was recovered as metaboHtes from urine, and excretion of metaboHtes in the urine came to an end four hours after exposure ended. DEBT did not accumulate in the skin, and only a small (less than 0.08%) amount ended up in feces. Curiously, less has been absorbed through skin from 100% DEBT appHcation (3—8%, mean of 5.6%) than from 15% alcohol appHcation (4—14%, mean of 8.4%). These results have been described as consistent with previous absorption/metaboHsm studies using guinea pigs, rats, and hairless dogs. Other pubHcations on DEBT toxicology have been cited (92). 

As was the case with guinea pigs, the few acute lethality studies of phosgene in rabbits do not contain experimental details such as strain or gender, number of animals exposed, or analytical methodology. These less than adequate studies are summarized in Table 1-9. 

In another study, Hartley guinea pigs (five per group) were exposed to phosgene at 0, 0.25, or 0.5 ppm for 4 h (Slade et al. 1989). The exposure chamber and atmosphere generation and measurement systems were similar to those used by Hatch et al. (1986). The LFP concentrations were measured 16 to 18 h after exposure. These investigators found that the LFP concentrations were elevated by 90% in animals exposed to phosgene at 0.25 ppm and 250% in animals exposed at 0.5 ppm, when compared with controls. 

A benzopyran derivative, RP-58866 (70) is under development by Rhone-Poulenc. Patch clamp studies in guinea-pig ventricular myocytes indicate that RP-58866 inhibits the inward rectifying potassium current (7ki) with no effects on the delayed rectifier, ATP-sensitive potassium currents or calcium currents [200]. RP-58866 increases APD90 of Purkinje fibres by about 45% at 0.3 yuM without affecting K ax [201]. The compound was effective... 

The quinolinone derivative, OPC-88117 (73), is yet another compound described as possessing both Class I and Class III electrophysiological activities. Studies in guinea-pig papillary muscle showed that OPC-88117 at 30 increased APDgo by about 15% and decreased F ,ax by only 4% however, at 100 /iM APDgo was prolonged by 23 % and was decreased by 23 % [206]. Further experiments in isolated rabbit hearts demonstrated that OPC-88117 increased atrio-His bundle (A-H) and His bundle-ventricle (H-V) conduction times and refractory periods with a profile that was similar to, but more potent than that of lidocaine [207]. 

The most recent reports on the action of the water soluble toxin from G, toxicus concluded that this toxin, referred to as maitotoxin, invokes an unmediated stimulatory (contractile) response on contact with guinea pig ileal smooth muscle preparations. Furthermore, this response was said to be due to an activation of calcium channels in the smooth muscle membranes (J7). Previous studies of this toxin from the same source indicated that it produces an inhibitory effect on guinea pig atrial muscle (28, 19). 

In a multispecies study, rabbits, guinea pigs, and rats were exposed 7 hours/day, 5 days/ week to levels of 150, 800, and 1200ppm. At 12 00 ppm all animals except for one rat died after a single exposure. At 800 ppm fractional mortality occurred after repeated exposures. At 150ppm four of five rats and two guinea pigs survived 70 hours of exposure, but one rabbit died after only 7 hours. Effects were irritation of the respiratory tract and eyes with the development of corneal opacities. 

Hie first efficacy studies were performed with guinea pig l-ASP, but bulk preparation of the enzyme turned out not to be feasible. Large-scale production... 

Acute toxicity of PCDEs has been studied in guinea pig, rabbit, rat, and trout [13, 81-83], Guinea pig is quite sensitive to PCDEs. Lethal doses of tetra- through hexaCDEs were between 0.05 g kg-1 and 0.1 g kg-1 after 30 days in a single dose oral feeding study [12, 13]. Repeated oral feeding (20 doses) of rabbits with hexaCDEs have caused liver injuries at 0.001 g kg1 (1 mg kg-1) dose [12,13]. 

Photosensitization potentials and cross-reactivities of ketoprofen, suprofen, tiaprofenic acid, and benzophenone have been studied in guinea pigs (192). Ketoprofen and benzophenone were the strongest photosensitizers. Crossreactivity was most frequent after sensitization with... 

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