摘要:

The interaction between nitric oxide (NO) synthesized in one cell and the haem group of cytosolic guanylate cyclase located in target cells to form NO‐haem‐guanylate cyclase represents a unique signal transduction mechanism that links extracellular stimuli to the synthesis of cyclic GMP in nearby target cells. Autacoids, neutrotransmitters, and macrophage‐ and neutrophil‐activating factors interact with selective extracellular receptors to trigger formation of NO from L‐arginine. NO may be viewed as a second messenger. The NO diffuses into adjacent target cells and causes haem‐dependent activation of guanylate cyclase, thereby stimulating cyclic GMP accumulation. Guanylate cyclase‐bound haem serves as a transducer in transferring the signal from NO to guanylate cyclase. Cyclic GMP acts as a third messenger in causing vascular smooth muscle relaxation, inhibition of platelet aggregation and adhesion, and modulation of macrophage, neutrophil, and other phagocytic cell functions. The unique physical and chemical properties of NO allow it to function as an intercellular modulator within a localized environment. This intercellular or transcellular signaling mechanism involving a common signal transduction mechanism permits the rapid initiation of localized complementary cellular functions leading to increased local blood flow, inhibition of local thrombosis, and modulation of phagocytosis and

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00772.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00773.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

An antibody raised against rat P450dbl was used to examine the heterogeneity of the human enzyme involved in the sparteine/debrisoquine polymorphism. The extent to which the antibody was able to inhibit sparteine metabolism varied in different human livers (10–80%, n = 9) and reflected the amount of sparteine metabolism carried out by the polymorphic P450IID6 in individual liver specimens. The individual sample variation in inhibition by the antibody correlated with the inhibition caused by quinidine, a prototype competitive inhibitor of the P450IID6 enzyme active site. Western immunoblots of the liver microsomes confirmed that the variation in the inhibition of sparteine metabolism by this antibody reflected the amount of P450IID6 protein. In addition, a detailed study of one of the livers (K 19) which demonstrated a lack of inhibition by the antibody was performed which confirmed the lack of P450IID6 in this liver specimen and suggested that the nascent sparteine metabolism activity was due to other forms of P45

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00774.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

This study reports the validation of an automatic assay for milk triglycerides, as well as the association between milk xenobiotic concentrations and milk triglycerides. The correlation between this assay and a gravimetric reference method for total fat was good (r = 0.997). Triglycerides and xenobiotics were measured in breast milk sampled from one mother. She received two water‐soluble drugs, tetracycline and doxycycline in two courses. The levels of organochlorines (DDE, PCB) were also measured and related to those of fat in milk samples from this mother. These and previous results indicate that milk triglyceride variations influence the concentrations of lipophilic xenobiotics in mil

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00775.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The toxic effects produced by 2, 3, 7, 8‐tetrachlorodibenzo‐p‐dioxin (TCDD) and its congeners include inhibition of lymphoid development. We have previously found an inhibition of B‐cell development in the bursa of Fabricius of chick embryos treated with TCDD congenersin ovo. In the present study, the bursae of ten‐day‐old chick embryos were removed and cultured on filter paper for 24 hr in media with or without TCDD or 3,3′,4,4′‐tetrachloroazoxybenzene (TCAOB). Following culture, the bursae were transplanted onto the chorioallantoic membrane (CAM) of ten‐day‐old eggs of the same strain or of a strain expressing a different B‐cell surface alloantigen. After 5 days on the CAM the number of B‐cells was determined or the grafts were sectioned for subsequent immunohistochemistry. Results were as follows: 1) A lower number of lymphoid cells (dose dependent) was observed in the TCDD‐treated transplants amounting to 40–50% of that in the controls at 10‐9M TCDD. Higher concentrations of TCDD compromised survival of the grafts. A single concentration of TCAOB (10‐8M) was tested, resulting in a lymphoid cell number of 60% of that of the controls. 2) The bursal epithelium showed relatively normal development even in cases where B‐cell development was affected. 3) Lymphoid cells in the grafted bursae originated from the embryo of the host egg. These findings suggest that the TCDD congeners had a direct effect on the bursa of Fabricius, leading to an inhibition of lymphoid development. It is likely that the microenvironment is affected by these compounds, thus resulting in a decrease in the attraction of stem cells and/or in the capacity to induce pr

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00776.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The cardiovascular effects of two organophosphorus, paraoxon and soman, as well as of antidotes advocated in the treatment of these intoxications have been investigated using a computerized analysis of arterial blood pressure in conscious unrestrained rats. Intravenous administration of paraoxon as well as of soman produced a marked, sustained and dose‐related increase in blood pressure associated with a bradycardia. Pyridostigmine, a quaternary carbamate, neither altered blood pressure nor heart rate. Benzodiaxepines, such as diazepam or loprazolam, and atropine induced a dose‐dependent tachycardia while pralidoxime decreased heart rate. A complete therapeutic scheme including the intravenous administration of pyridostigmine 10 min. before a postpoisoning therapy made of pralidoxime, diazepam and atropine induced a transient tachycardia, which was followed, after a return to control values, by a second and more stable tachycardia concurrently to a slight hypertension. Postpoisoning therapy alone suppressed the pressor effect of soman within a few minutes after its administration. Afterwards, this therapy reduced the importance of the cardiovascular effects produced by soman. Pyridostigmine pretreatment decreased the protection afforded by postpoisoning therapy in soman‐intoxicated rats. These results show that postpoisoning therapy with pralidoxime, diazepam and atropine has a noteworthy efficacy against cardiovascular manifestations of soman intoxications in th

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00777.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The effects on behaviour of single subtoxic doses of two potent organophosphorous compounds, sarin (isopropyl methylphosphonofluoridate, 12.5 and 50 μg/kg, intraperitoneally) and soman (pinacolyl methylphosphonofluoridate, 4 and 20 μg/kg, intraperitoneally) were studied in male Wistar rats. In the open field test, soman dose‐dependently decreased rearing and ambulation and increased non‐mobile exploration. The higher dose of sarin changed only the rearing and grooming behaviour. Sarin and soman decreased locomotor activity on the Animex for at least one hour at the beginning of the monitoring period. In the doses used, both organophosphates inhibitied acetylcholinesterase (AChE) activity significantly in the blood. The results suggest that small doses of sarin and soman have inactivating effects on the behaviour of rats. Although the findings cannot be extrapolated directly to behavioural changes in man, they indicate that subtle behavioural dysfunctions could also occur in humans at exposures which do not cause acute tox

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00778.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Twenty volunteers were exposed to 191 ± 7 p.p.m. 1,1,1‐trichloroethane or 50 ± 2 p.p.m. perchloroethylene vapour for 6 hr. They were then evaluated for their rate of caffeine metabolism, mephenytoin hydroxylation and debrisoquine hydroxylation. Seven subjects were idendified as ‘fast acetylators’ of caffeine and one person as a slow metabolizer of debrisoquine. The “slow acetylators” exposed to perchloroethylene excreted an average of 3.83 ± 0.35 mg trichloroacetic acid within 24 hr (N = 13, ± S.E.) and the ‘fast acetylators’ 3.58 ± 0.48 mg (N = 7, ± S.E.). The excretion of trichloroethanol by the same persons after 1,1,1‐trichloroethane exposure was 14.1 ± 1.12 mg and 16.7 ± 1.48 mg, respectively. The excretion of trichloroacetic acid in the latter exposure varied significantly between the seven ‘fast’ and 13 ‘slow acetylators’ (0.43 ± 0.08 mg versus 1.03 ± 0.19 mg; ± S.E.; P = 0.037). A multiple linear regression analysis confirmed this association when other factors, such as body weight, creatinine clearance, smoking habit and alcohol consumption, were taken into account. One volunteer proved to be a poor hydroxylator of debrisoquine and excreted half the amount of trichloroacetic acid in the perchloroethylene exposure and half the amount of trichloroethanol in the 1,1,1‐trichloroethane exposure compared to the others. A reduction in the solvent metabolism could thus be predicted by the debrisoquine test. On the other hand, the caffeine test predicted faster oxidation of trichloroethanol which could be of toxicological and pharmacological importance

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00779.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Phosphamidon was detected by thin‐layer chromatography (TLC) from various CNS regions of the rats intoxicated with three doses (1.0, 1.5 and 2.0 mg/kg body‐weight) intraperitoneally daily for seven days. A distinct dose‐related increase in its concentration was observed in all investigated areas of the CNS. Regions with higher gray matter composition showed greater uptake of phosphamidon compared to those rich in white matter. This is in accordance with our previous study (Naqviet al.1988) revealing similar pattern in the effect of phosphamidon on the phospholipids in the

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00780.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Female rats (SIV‐50, Sprague Dawley) given a diet enriched with corn oil (10% and 25% addition to rat chow, w/w) for four weeks showed changes in the energy metabolism of heart, liver and kidneys, that is, changes in oxygen consumption and uncoupling of oxidative phosphorylation of heart, liver and kidney mitochondria, concomitant to a decrease in heart mitochondrial creatine kinase activity and an increase in heart mitochondrial creatine content. The high fat diet also affected calcium binding and Na/K‐, Mg‐ and Ca‐ATPases of a cardiac myocyte membrane fraction. Lipid feeding also led to increase (biphasic and transient) of phospholipids, triglycerides and free fatty acids in the three organs studied, but in no case to hyper

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00781.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY