The amelioration of the suffering associated with spinal cord injury with subperception transcranial electrical stimulation.

STUDY DESIGN: Double blind, partial crossover. OBJECTIVES: To evaluate the analgesic activity of a novel cranial electrostimulus in people with spinal cord injury (SCI). SETTING: Hereward College, a residential centre that provides educational facilities for students with disabilities. METHODS: Subjects with SCI experiencing chronic pain were randomly assigned into two groups, one of which received sham and the other transcranial electrostimulation treatment (TCET) on two occasions daily for four successive days. After a 'wash-out' period of 8 weeks all subjects returned and received the identical stimulus that the treated cohort received on the first arm of the study. RESULTS: Pain measurements applied before and after each session indicated that the pain decreased in the treated group to 51% of that reported at the commencement of treatment; reported pain intensity did not decrease significantly in the sham treated subjects. The same (sham) subject group reported experiencing 59% of the pain at the end of the second arm of the study (TCET) as on the first arm (sham). No significant differences were determined between the mood of all subjects estimated before and after each sham or TCET treatment session. The reported analgesic, and combined antidepressant and anxiolytic drug use in subjects receiving TCET on the second arm of the study, was 46% and 53% respectively of the average pre-study drug use. No similar decrease in the use of the drugs was noted in the same subjects after sham treatment on the first arm of the study. Salivary cortisol determinations made prior to and after each sham and treatment session implicated this corticoid in the pain-relieving mode of action of the treatment, but could not be associated with any changes in mood. Subjects receiving TCET had significantly higher urinary 3-methoxy-4-hydroxy-phenylglycol (MHPG) output after the TCET treatment period than sham stimulation, implicating increased central noradrenaline (NA) metabolism in the observed effects. CONCLUSION: The subjects reported less pain during, and immediately after receiving this transcranial treatment, although they were using less medication than when receiving sham treatment.

Abnormal antioxidant defence in some tissues of congenitally obese mice.

The concentration of lipoperoxides (estimated as thiobarbituric acid-reactive material) and some components of the antioxidant defence system have been compared in various tissues of lean and congenitally obese mice. NADPH-stimulated lipoperoxide generation in vitro was significantly higher in microsomes (microsomal fractions) prepared from obese hepatic tissue than lean. Plasma, liver and brain lipoperoxide concentration was significantly higher in obese mice. In blood derived from obese mice the concentration of non-enzymic antioxidants including caeruloplasmin and vitamin A was higher, but hepatic retinol concentration was lower in these animals. In all the tissues assayed the glutathione peroxidase activity against H2O2 was less than its activity against cumene hydroperoxide. Assayed with either substrate, glutathione peroxidase activity was significantly higher in the brain and blood of obese mice than their lean counterparts. Conversely, liver glutathione peroxidase was decreased in obese animals, representing 43% of the activity of the lean-mouse liver enzyme against H2O2 and 81% of the cumene hydroperoxide-reducing activity. The liver of obese mice had significantly less, and the kidneys more, oxidized glutathione than the corresponding tissues of lean mice. Further investigations on hepatic tissue indicated that glutathione reductase activity was lower in the obese animals, but there was no significant difference between glucose-6-phosphate dehydrogenase activity in obese and lean mice.

The influence of cold restraint stress on some components of the antioxidant defence system in the tissues of rats of various ages.

Rats of various ages were subjected to stress by confinement in restraining cages at 2-4 degrees C. Analysis of the plasma of these animals revealed an elevation in corticosteroids of approximately 50% above the control level. The livers of all the groups of cold-restrained animals contained significantly more lipoperoxide (estimated as thiobarbituric-acid-reactive material) than did control hepatic tissue. The plasma of the 12-, 24-, and 32-wk-old groups of rats subjected to stressful treatment also contained significantly higher lipoperoxide levels. There was no significant difference between the lipoperoxide levels of the brain tissue of control or stress-treated rats. The activities of both glutathione peroxidase and glutathione reductase were increased in hepatic, but not brain, tissue of the stressed animals. The perturbation of the activities of these enzymes did not produce any significant change in the ratio of reduced, oxidized glutathione. The livers of the stressed animals had significantly less total glutathione than those of the controls.

Vitamin E retards the lipoperoxidation resulting from anticancer drug administration.

The administration of either 5-fluorouracil, methotrexate, cyclophosphamide or vincristine to rats produced an increase in liver and plasma, but not brain, lipoperoxide levels. There was no significant difference between the glutathione peroxidase activity in the liver and the brain tissue of cytotoxic drug-treated and control rats. Glutathione peroxidase activity was significantly lower in the erythrocytes of 5-fluorouracil-and methotrexate-treated rats than in control animals. The erythrocyte glutathione peroxidase levels of vincristine- and cisplatin-treated rats did not differ significantly from the control levels. Rats which received vitamin E supplementation concomitantly with 5-fluorouracil treatment had liver and plasma lipoperoxide levels which were significantly lower than those which had received only the anticancer drug. The tissue lipoperoxide levels in the vitamin E supplemented, 5-fluorouracil-treated rats were comparable with those of arachis oil-treated controls.

Serum galactosyl transferase levels in patients with advanced cancer.

Serum galactosyl transferase was significantly higher in patients with various types of cancer than in age-matched controls. The highest serum enzyme levels were observed in the breast and respiratory cancer, followed by ovarian and gastrointestinal tumours; whereas the enzyme activity in prostatic cancer patients was not significantly higher than in the control subjects. In the cancer patients the serum levels of this enzyme were not significantly higher in the presence of metastases. In terminally ill patients, the serum enzyme activity decreased proportionately in accordance with the progression of their disease.

Comparison of concentrations of some trace, bulk, and toxic metals in the hair of normal and dyslexic children.

Hair from dyslexic children, analyzed by flameless atomic absorption spectrometry, showed significantly higher concentrations of magnesium and copper than did hair from control subjects. The hair from dyslexic children also contained significantly higher concentrations of aluminum and cadmium than that from control children; the cadmium concentration exceeded the normal acceptable range. There were no significant differences in the case of lead, calcium, selenium, or mercury. Our results indicate that excessive cadmium burden could be implicated in this form of learning disorder.

The influence of zinc status on the anti-Lewis lung tumour activity of cisplatin and gallium.

Treatment of C57/BL mice with either cisplatin or gallium nitrate inhibited the growth and metastasis of the Lewis lung tumour and these anti-tumour agents also lowered the zinc levels of some tissues. Nutritional zinc deficiency or the deficiency arising from treatment with the chelating agent, penicillamine, also restricted tumour growth. Although the anti-tumour activity of cisplatin was enhanced in zinc-deficient mice, many of these animals died before sacrifice 14 days after tumour inoculation. The results indicate that zinc status could have considerable bearing on the therapeutic index of the mental-containing anti-cancer drugs.

The effect of isolation stress on some hepatic drug and carcinogen metabolising enzymes in rats.

Rats were subjected to stress by isolation for periods of up to eight days, which produced an elevation in plasma cortisol. In vivo drug metabolism as estimated by the plasma elimination rate of orally-administered antipyrine was not significantly affected by this treatment although there was an apparent decrease in the absorption rate of the drug. In vitro experiments on hepatic microsomal preparations derived from stressed animals indicate that this stress increased in the activity of some enzyme systems concerned with benzo(a)pyrene activation and this correlated with an increased binding of the carcinogen to DNA. The activity of conjugating enzyme which could catalyze the excretion of such carcinogens was not significantly altered. The results indicated that stress could have an important bearing on carcinogenesis by enhancing to a greater extent enzyme systems responsible for activation than those involved in the excretion of polycyclic aromatic hydrocarbons.

The effect of chloroform inhalation on hepatic glucuronidation and de-glucuronidation mechanisms.

The effect of 2, 4, 6 or 8 exposures to chloroform vapour on hepatic glucuronidating (UDPGA transferase) and de-glucuronidating (beta-glucuronidase) levels has been studied in rats. Successive treatments progressively decreased hepatic UDPGA transferase to a minimum of 53% of the control level. beta-Glucuronidase activity was increased two-fold after only two exposures and remained elevated for subsequent exposures. Cytochrome P450 levels decreased with each exposure. The level of this coenzyme in the treated animals remained lower than that of the control animals for at least 48 hours after treatment. UDPGA transferase was diminished to its lowest levels 9 hours after the final exposure to chloroform and did not achieve the control value for a further 48 hours. The beta-glucuronidase activity remained elevated for 12 hours after final exposure. The present experiment demonstrates that inhalation of toxic solvents such as chloroform decreases the glucuronidating capacity of the liver.

Hepatic function assessed (in rats) during chemotherapy with some anti-cancer drugs.

Using rats, we studied how best to assess hepatic damage after administering therapeutic doses of each of five anti-cancer drugs or of the hepatotoxin, carbon tetrachloride. As indexes, we compared measurement of the concentration of administered antipyrine in plasma with measurement in serum of alpha-fetoprotein or of the activities of five enzymes that reportedly best reflect hepatic damage. The biological half-life of antipyrine in the plasma was increased more than threefold on pretreating the rats with any of the five cytotoxic drugs or with carbon tetrachloride. In contrast, the concentrations of alpha-fetoprotein, alkaline phosphatase, gamma-glutamyltransferase, or glutamate dehydrogenase were not consistently increased. Of the enzymes tested in serum, aspartate aminotransferase and ornithine carbamoyltransferase best indicated hepatic impairment resulting from the treatment with anti-cancer drugs. Our results imply that determination of the pharmacokinetics of marker drugs such as antipyrine better indicates hepatic dysfunction induced by cytotoxic agents than does measurement of the enzymes liberated into serum as a result of damage to liver mitochondria.

Correlation between tumour size, metastatic spread and galactosyl transferase activity in cyclophosphamide-treated mice bearing the Lewis lung carcinoma.

Galactosyl transferase activity was measured in tumour and normal tissues of mice receiving cyclophosphamide treatment for Lewis lung carcinoma. Animals which responded to cyclophosphamide therapy had significantly smaller tumours with fewer metastases than the untreated mice. The level of galactosyl transferase was significantly reduced in the tumours which were inhibited by the cyclophosphamide treatment.

The effect of chronic ethanol intake on the growth and spread of some murine tumors.

The effect of chronic ethanol intake on the growth and spread of some murine tumors has been investigated. The treatment had no effect on the B 16 melanoma but tended to decrease the number of Ehrlich ascites cells. In the case of the Lewis lung carcinoma, administration of ethanol for two weeks tended to lower the number of metastases to the lung without significantly affecting the primary tumor size, whereas more prolonged ethanol intake decreased the weight of the primary tumor in addition to decreasing its dissemination.