摘要:

Abstract:Effects of fixed and fluctuating concentrations of m–xylene in air were studied on human psychophysiological functions. Nine healthy male volunteers were exposed to m–xylene 4 hrs a day, 3 hrs in the morning and 1 hr in the afternoon, with a 40 min. break in between. The subjects were sedentary or exercised at 100 W for 10 min at the beginning of each session in the chamber. The m–xylene concentrations in the air were fixed (8.2 μmol/1; 870 mg/m3) or fluctuated with peaks (5.2–16.4 μmol/1; 550–1740 mg/m3) but the TWA (8 hrs) concentration of m–xylene was always 4.1 μmol/1 (435 mg/m3). The two control days, with and without exercise, were similar to the exposure days, but without exposure. Reaction times were measured with a device in which subjects responded to visual and auditory stimuli. Body sway was measured with the subjects' eyes open and closed with a strain gauge transducer platform. Changes in reaction times did not correlate with m–xylene concentrations in the air. Changes of average and maximal body sway were, however, consistently negatively correlated with the intensity of the atmospheric exposure to m–xylene at the beginning of each session in the chamber. Physical exercise combined with exposure to m–xylene improved rather th

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb00012.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Abstract:The effect of varying concentrations of cadmium, copper, zinc, and selenite on the ativity of aryl hydrocarbon hydroxylase (AHH) of rat lungs was studiedin vitro.All the metals resulted in a strong inhibition of enzyme activity. Copper and zinc were more inhibitory to rat lung AHH than cadmium and selenite. There was an additive inhibition of AHH activity when copper or zinc was added in the presence of cadmium. EDTA or glutathione exerted a protective effect on cadmium–induced inhibition of AHH activity. Prior incubation of the microsomes with N–ethylmaleimide, a thiol–blocking agent, had no effect on the inhibition of AHH activity caused by cadmium. Addition of cadmium along with zinc–thionein resulted in increased inhibition of rat

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb00013.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Abstract:Findings made by computerized tomography scanning of pelvis of patients suggested that the majority of injections intended to be intramuscular in fact are delivered in the fat tissue. This finding has raised the question what difference it makes when drugs are injected intramuscularly or intralipomatously. We have studied local toxicity after intramuscular or intralipomatous injection of different drugs in pigs, which have a subcutaneous layer of fat comparable to that of man. The pigs were killed 1, 3, 7 or 14 days after injection of antibiotics, vitamins, neuroleptics, diazepam, digoxin, pentazocine, sulphadimidine and vehicles. The tissues at the injection site were examined macro– and microscopically. In another series of experiments an aqueous or two different oily preparations of the neuroleptic drug cis(Z)–clopenthixol were given intramuscularly or intralipomatously to pigs and a series of blood samples were taken for drug level determination. The tissue examinations showed that all drugs causing local muscle damage after intramuscular injection caused considerably less extensive damage with a faster regeneration after intralipomatous injection. The pharmacokinetic study showed that there was virtually no difference between plasma–concentration–time curves after intramuscular or intralipomatous injection. Our findings indicate that intralipomatous injection of irritating drugs is better tolerated than intramuscular injection since intralipomatous injection causes less local toxicity. Our findings also suggest that the pharmacokinetics are not different. However, further studies are required to substantiate whether the findings are of general r

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb00014.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Abstract:The effects of glyceryl–trinitrate (GTN) and dipyridamole (DIP) on relaxation of bovine coronary arteries and on inhibition of aggregation of human platelets have been studiedin vitrowith special reference to the cyclic GMP (cGMP) system. GTN had a dose–dependent relaxant effect on bovine coronary arteries, and at a high concentration (10–5M) it had an inhibiting effect on platelet aggregation. The effects were associated with an increase in the cGMP levels of the tissues. DIP (5 × 10–7M respectively 5 × 10–6M) potentiated the coronary artery relaxation induced by GTN (10–8M) and the inhibition of platelet aggregation caused by GTN in the concentrations 10–7–10–4M. The potentiation was associated with higher levels of cGMP than those produced by GTN alone, at least in bovine coronary arteries. However, at a concentration of 10–4M, GTN, in combination with DIP, caused a significant fall in the cGMP level compared to GTN alone. GTN and DIP were not found to significantly increase the cAMP levels in the concentrations tested. DIP was shown to inhibit phosphodiesterase (PDE) from both platelets and bovine coronary arteries. This might be one of the possible mechanisms that can explain the above mentioned potentiation. It is suggested that the combination of DIP+GTN may be of some clinical importance since the potentiating effects were seen at concentrations comparable to the therapeutic plasma concentration fo

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb00015.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Abstract:N–Acetyl, N–propionyl, and N–pivaloyl derivatives of taurine were synthesized by applying a modified Schotten–Bauman method starting from taurine and using the corresponding acid chloride or acid anhydride for direct acylation reactions. The central nervous system actions of these lipid soluble taurine derivatives, which were presumed to pass the blood–brain barrier, were studied and compared to those of taurine in mice. A large dose (15 mmol/kg) of intraperitoneally administered taurine lengthened the pentobarbitone induced sleep by 30%. N–Pivaloyltaurine was 45 times more potent but not more effective than taurine. Neither N–acetyl– nor N–propionyltaurine lengthened the pentobarbitone induced sleep in doses up to 3 mmol/kg. Intraperitoneally administered N–pivaloyltaurine depressed the locomotor activity in a smaller dose and for a longer period than taurine. However, when administered intracerebroventricularly neither N–acetyl– nor N–pivaloyltaurine altered the locomotor activity in three times larger dose than in which taurine clearly depressed it. Intraperitoneally administered N–pivaloyltaurine decreased the rectal temperature slightly more than taurine, whereas intracerebroventricularly administered taurine was clearly more potent in inducing hypothermia than its acyl derivatives. Intraperitoneally administered N–pivaloyltaurine was about three times more potent than taurine in increasing the striatal concentration of dopamine. Intraperitoneally administered N–pivaloyltaurine only in a very large dose (3 × 15 mmol/kg) slightly and transiently increased the cerebral taurine concentration. Carboxylesterase inhibition by bis–p–nitrophenyl phosphate (BNPP) did not modify this increase. Furthermore, BNPP pretreatment modified neither the hypothermic nor the striatal dopamine concentration elevating effects of N–pivaloyltaurine. Our results suggest that N–pivaloyltaurine possesses taurine–like pharmacological actions. It is not converted to taurine to produce these actions. When administered intracerebroventricularly it is less potent than taurine. However, when administered intraperitoneally it is more potent than taurine because it seems to pass the blood–brain–barrier more easily than taurine. Thus N–pivaloyltaurine could be used to study the behavioural an

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb00016.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Abstract:Allyl chloride, bromide and iodide were investigated for their properties as sensory irritants in mice. The concentrations of the chemicals necessary to depress the respiratory rate by 50% (RD50) within the first 10 min. of exposure due to irritation of the upper respiratory tract were 2330, 257 and 79.8 p.p.m., respectively. No pulmonary irritation was observed. In the period 20 to 30 min., however, pulmonary irritation was observed for allyl bromide and iodide. The effect was not prominent in non–cannulated mice probably due to the scrubbing effect of the nose. According to RD50 values, thermodynamic activity as well as apparent association rate with the receptor the sensory irritating potencies of the halides were low compared to those of allyl alcohol, acetate, and ether. A mechanistic explanation could not be ascribed to metabolites, lipophilicity or chemical reactivity. Only a hydrogen bond donor ability of the receptor offered an explanation. As many industrial chemicals e.g. alcohols, ketones and esters can function as hydrogen bond acceptors this receptor–feature cannot be overemphas

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb00017.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Abstract:The metabolism of debrisoquine, 7–ethoxyresorufin and benzo(α)pyrene has been studied in human liver microsomes. There was a significant correlation (r = 0.70, P<0.05) between debrisoquine hydroxylation and 7–ethoxyresorufin 0–deethylation among various livers, and debrisoquine inhibited 7–ethoxyresorufin deethylation competitively. These results suggest that debrisoquine and 7–ethoxyresorufin may be metabolised by a common P–450 form in human liver. The effect of cytochrome P–450 inducers on the metabolismofthe three substrates was also examined in rat liver. Debrisoquine hydroxylation was not enhanced by phenobarbitone, β–naphthofla

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb00018.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Abstract:Fenflumizole is a substituted triaryl–imidazole with anti–inflammatory activity. Its disposition in man was studied after single intravenous and oral doses to 8 healthy male volunteers. Formation of the prostanoids thromboxane B2(TXB2) and 6–keto–prostaglandin F1α(6–k–PGF1α) in clotting blood was studied concomitantly. The pharmacokinetics after intravenous doses (0.1 mg/kg) could be fitted to a three compartment model and the half–lives (t1/2) corresponding to the three phases were 2 min., 1 hour and 15 hours, respectively. The volume of distribution was 386 1 and the plasma clearance 0.5 1 per min. Oral doses (0.5 mg/kg) were rapidly absorbed (t1/2= 0.2 hr) and the following elimination from plasma had two phases with half–lives of 1 hour and 14 hours. Bioavailability was 50% due to a pronounced first–pass effect. The two metabolites mono– and didemethylfenflumizole were detected after both oral and intravenous doses and their maximum plasma concentrations occurred after 1–2 hours irrespective of the administration route. A concentration dependent depression of prostanoid formation was seen, the IC50 for TXB2and 6–k–PGF1αbeing

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb00019.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Abstract:A recently discovered neurotoxic compound, l–methyl–4–phenyl–l,2,3,6–tetrahydropyridine, has been found to cause a parkinsonian–like syndrome in man and monkey, but not in laboratory animals such as rat, mouse and guinea pig. MPTP seems to selectively destroy the melanin containing dopaminergic cells in pars compacta of substantia nigra. Lower mammalian species do not have melanin in these cells, which indicates that the presence of neuromelanin may be of importance for the development of MPTP–induced lesions. By means of whole–body autoradiography of3H–MPTP in mice, accumulation and retention was observed in the dopaminergic pathways, in locus caeruleus and in structures in the medulla oblongata and spinal cord. A high uptake was also seen in melanin–containing tissues such as in the eyes of pigmented mice. MPTP has earlier been found to have high affinityin vitrofor dopamine melanin, which is similar to the pigment in substantia nigra. The typical features of the MPTP–induced neurotoxicity with destruction of pigmented nerve cells and development of parkinsonism may be due to accumulation and retention of MPTP and its metabolites in these cells. In species with pigmented nerve cells, such as man and monkey, the accumulation may be much more pronounced because of the melanin affinity of MP

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb00020.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Abstract:The activity of carboxylesterase and cholinesterase in plasma, liver and lung of young rats at different ages (5–31 days old) have been measured. The cholinesterase activity in the tissues of both sexes were almost constant during the development, and were similar to adult male activity. The carboxylesterase activity towards methyl butyrate and 4–nitrophenyl butyrate in plasma of both sexes increased from negligible (5 days old) to adult male value (31 days old). The carboxylesterase activities in liver increased markedly during the period, whereas the lung activities increased only slightly. The toxicity of soman was 6–7 fold higher in 5 days old rats compared to 30 days old rats. The decrease in toxicity correlated well with the increase in plasma carboxyles

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb00021.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY