Preliminary report: the short-term effects of direct p53 DNA injection in primary hepatocellular carcinomas.

A pilot study, to assess the therapeutic potential of percutaneous injection of wild-type p53 (wt-p53) in five patients with primary hepatocellular carcinoma is reported. Three of the five patients showed objective tumor response with reduction of the tumor volume on computed tomographic (CT) scan measurements as well as a significant fall of serum alphafetoprotein. Much further work will be needed to elucidate the mechanism of action.

In vivo and in vitro studies on the effect of larvin and cypermethrin on adenosine triphosphatase activity of male rats.

Liver is removed from albino rat and assayed for total adenosine triphosphatase (ATPase) activity following administration with single and repeated doses of larvin and cypermethrin. The data indicate that the total (Na+, K+; Mg2+) dependent ATPase in the liver tissue is significantly inhibited by single and repeated doses of both insecticides. This inhibition is more pronounced by the repeated dose of cypermethrin than that of larvin. The in vitro study revealed that the inhibition encountered by different concentration of both larvin and cypermethrin is of the irreversible non-competitive type. This data indicate that these insecticides can cause biochemical and histopathological changes in the liver ATPase activity which may inhibit several biochemical functions of ATPase system such as: the active transport of metal ions, oxidative phosphorylation of liver cells and generally the muscle contraction.

Studies on serum beta-glucuronidase activity and urinary tryptophan metabolites in human fascioliasis.

In the last few years, human fascioliasis has been reported more frequently from different parts of the world including Egypt. The present work aimed to study the ability of fascioliasis affected patients to metabolize tryptophan and to explore how this disease can affect the activity of the hydrolytic lysosomal enzyme beta-glucuronidase. Liver and kidney functions and complete blood pictures of the studied patients were considered. Eleven tryptophan metabolites together with 4-pyridoxic acid, the major metabolite of vitamin B6, were determined. Fascioliasis showed an abnormal pattern of tryptophan metabolism which resembled that described earlier by Kupke and Knapp and which indicated that those patients were suffering from vitamin B6 deficiency. This conclusion was proved by the decreased levels of 4-pyridoxic acid. Abnormally high levels of beta-glucuronidase were also encountered in the fascioliasis cases which points to the liver damage caused by the fluke.

An experimental study on the effect of praziquantel and oltipraz on some lysosomal enzymes.

The in-vivo effect of the schistosomicidal drugs praziquantel and oltipraz on the activities of the liver lysosomal enzymes in Schistosoma mansoni-infected and non-infected mice was studied. The effect of S. mansoni infection and the administration of the schistosomicidal drugs on the activities of beta-glucuronidase, acid ribonuclease and alpha-naphthyl acetate esterases may be considered as indices for carcinogenicity. Drugs were given orally in subcurative doses, either in a single dose of 400 mg kg-1 for praziquantel or in five daily doses of 50 mg kg-1 oltipraz. The increase in enzymatic activities in infected animals was attributed to deranged metabolic function as a result of liver cell injury. Treatment of uninfected animals with either praziquantel or oltipraz significantly increased the activities of the three lysosomal enzymes. Praziquantel possesses reversible and less toxic effects on the liver than oltipraz. The role of these antischistosomal drugs cannot be ignored as a possible aetiological factor implicated in the process of carcinogenesis associated with schistosomiasis infection through modulation of the operating potential of the enzymes concerned with detoxification, protein and fat metabolism.

In vivo studies on the effect of some insecticides on the hepatic activities of L-tryptophan 2,3-dioxygenase and pyridoxal phosphokinase of male mice.

The effect of Dimethoate, Carbaryl and Permethrin on the activities of liver L-tryptophan 2,3-dioxygenase (total-, holo-, and apo-forms) and pyridoxal phosphokinase of male mice was investigated. Dimethoate inhibited both enzyme systems after single and repeated dose treatment; except the dioxygenase holo-enzyme after repeated doses. Single dose of Carbaryl treatment inhibited the pyridoxal phosphokinase, total and holo-enzyme of L-tryptophan dioxygenase. However, the repeated dose treatment do not affect both enzyme systems. Permethrin inhibited only total-, holo- and apo-enzymes of L-tryptophan dioxygenase whereas repeated administration has no significant effect on both enzymes. The data indicate that these insecticides may induce abnormal tryptophan metabolism through which some endogenous bladder carcinogens are formed.

The correlation between certain tryptophan metabolites and the N-nitrosamine content in the urine of bilharzial bladder cancer patients.

The present work is an up-to-date approach to study the correlation between the excretion pattern of tryptophan metabolites along the kynurenine pathway (after loading with 2 gm. L-tryptophan), and the N-nitrosamine content in urine of bilharzial bladder cancer patients. The control group was composed of healthy subjects who had no reported history of S. haematobium infection and no current bacterial cystitis. The N-nitrosamine content was determined by the colorimetric method of Eisebrand and Preussmann (1970). It was demonstrated that 64 per cent of the patients metabolized the tryptophan load abnormally and the others metabolized it almost normally. Moreover, the N-nitrosamines were present in 43 per cent of controls and 93 per cent of patients have these derivatives in higher values. The presence of an inverse correlation between certain tryptophan metabolites, shown previously to be bladder carcinogens, and the N-nitrosamine content, especially after loading, was interpreted in view of the possible conversion of some tryptophan metabolites into N-nitrosamines either under endovesical conditions or during the execution of the colorimetric determination of these compounds. Therefore, thorough investigation is urgently needed to study the origin of these urinary N-nitrosamines. Moreover, improved method(s) for their colorimetric determination are also urgently needed.

In vitro studies of the effect of metal ions, EDTA and their mixtures on kynurenine aminotransferase and kynurenine hydrolase.

In the present study use was made of the chelating ability of EDTA and the activating property of some metal ions Ca(II), Mg(II) or Mn(II) to counteract the inhibitory effect of Cu(II), Co(II), Pb(II) or Zn(II) ions on the B6-dependent kynurenine hydrolase and on kynurenine aminotransferase. These may be of help in studying the therapeutic trials in the treatment of metal poisoning. EDTA was able to counteract the inhibitory effect of Cu(II) or Co(II) on kynurenine aminotransferase and partially counteract the inhibitory effect of Cu(II), Co(II) on kynurenine aminotransferase and partially counteract the inhibitory effect of Cu(II), Co(II), Pb(II) or Zn(II) ions on kynurenine hydrolase. The difference in the response of the two B6-dependent enzymes to EDTA is attributed to the difference in the functional groups involved in the active site(s) of the two apoenzymes. Moreover, Mn(II), Ca(II) and Mg(II) ions have the ability to counteract some of the inhibitory effect of these metal ions.