LE Magazine, August 2000 - Medical Updates

August 2000
Table Of Contents

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2. IGF-1 is not a useful marker of prostate cancer

   Full source: BJU International 83 (9), 996-999

   A study determined whether the use of blood levels of insulin-like growth factor 1 (IGF-l) is more efficient in predicting prostate cancer in those undergoing prostatic biopsy than the use of prostate specific antigen (PSA) levels. Ninety-four individuals required biopsies of their prostate. Thirty-seven were found to have prostate cancer and 57 had no evidence of malignancy. There was no statistical difference in blood IGF-l levels between these groups. The PSA level and age of the individuals differed significantly between the groups. There was no correlation between IGF-l and PSA levels, and even when the age difference in the groups was considered, there was still no significant relationship between IGF-l levels and the incidence of prostate cancer. In individuals with a PSA level of 4-20 g/L there was no statistically significant difference in IGF-l levels between the groups. Thus, blood IGF-l level as a tumor marker does not help to predict prostate cancer. PSA level and even age were better predictors of the presence of prostate cancer than were IGF-1 levels.

   
   
   

3. NAC boosts glutathione level in immune system

   Full source: American Journal of Physiology-Lung Cellular and Molecular Physiology, 1999, Vol. 277, lss 4, pp L743-L748
   
   A study evaluated the critical role of glutathione (GSH), (an endogenous antioxidant) in silica-induced oxidative stress, cytotoxic (cell toxicity), and genotoxicity (DNA damage that may cause mutation or cancer) in rat macrophages (immune cells). The intracellular GSH content was modulated by N-acetylcysteine, a GSH precursor, and buthionine sulfoximine, a GSH synthesis inhibitor. It was found that the silica-induced stress led to a dose- and time-dependent decrease in GSH content in the macrophages. N-acetylcysteine (NAC) increased intracellular GSH level and protected against silica-induced free radical formation, lactate dehydrogenase leakage, and DNA strand breaks in macrophages. In contrast, buthionine sulfoximine pretreatment depleted cellular GSH and enhanced the susceptibility of macrophages to the cytotoxic and genotoxic effects of silica. Glutathione plays a critical role in protecting against cell injury, most probably through its antioxidant activity.
   
   

   
   
   

4. Beneficial effects of NAC in diabetes

   Full source: Diabetes, 1999, Vol. 48, 1ss 12, PP 2398-2406

   Free radicals are produced under diabetic conditions and possibly cause various forms of tissue damage in those with diabetes. A study examined the involvement of free radicals in the progression of pancreatic cell dysfunction in type 2 diabetes and evaluated the potential usefulness of N-acetyl-L-cysteine (NAC) in the treatment of type 2 diabetes. The treatment with NAC retained glucose-stimulated insulin secretion and moderately decreased blood glucose levels showing possible protection of pancreatic beta-cells against glucose toxicity. The beta-cell mass was significantly larger in the diabetic mice treated with NAC than in the untreated mice. The antioxidant treatment suppressed apoptosis (programmed cell death) in beta-cells without changing the rate of beta-cell proliferation. The antioxidant treatment also preserved the amounts of insulin content and insulin mRNA, and the activity of a beta-cell-specific transcription factor ( transfer of genetic code information from one kind of nucleic acid to another), was more clearly visible in the nuclei of islets of Langerhans cells of the pancreas. Thus, the antioxidant treatment with NAC can exert beneficial effects in diabetes, with preservation of beta-cell function. This finding suggests a potential usefulness of antioxidants for treating diabetes and provides further support for the implication of free radicals in beta-cell dysfunction in diabetes.

   
   
   

5. Effect of Ginkgo/drug combination on pancreatic cancer

   Full source: Arzneimittel-Farschung-Drug Research, 1999, Val. 49, Is 12, PP 1030-1034

   A study evaluated the efficacy and tolerability as well as the quality of life under treatment with a drug, 5-fluorouracil (5-FU), combined with ginkgo biloba extract (GEE) in 32 individuals with locally or metastatic advanced pancreatic cancer. The treatment was repeated every three weeks until progression. Response to therapy was evaluated after 2 and 4 treatment courses. Progressive disease was observed in 22 ( 68.8 % ) individuals, no change in 7 (21.9 % ) and partial response in 3 (9.4 % ). The overall response was 9.4 %. Adverse events were judged as related to the drug 5-FU and consisted of liver toxicity. In comparison with the results of the studies with the drug, gemcitabine, the combination of 5-FU/GEE shows comparable response rates. The toxicity of the 5-FU/GEE combination was low. The results suggest a good benefit-risk ratio of the combination of the drug 5-FU and GEE in the treatment of pancreatic cancer.

   
   
   

6. Melatonin and deprenyl protect against free radical induced brain damage

   Full source: British Journal of Pharmacology, 1999, Vol. 128, Iss 8, PP 1754-1760

   A study examined the effect of melatonin, a potent antioxidant, and deprenyl, a neuroprotectant, as inhibitors of use of an excitotoxic compound, quinolinic acid. Quinolinic acid induces damage to the hippocampus of the brain. Co-administration of melatonin prevented the Quinolinic acid (120 nmols) induced damage to the pyramidal cell layer of the brain. Quinolinic acid increased the formation of lipid peroxidation products from hippocampal tissue and this effect was prevented by melatonin. Deprenyl also prevented quinolinic acid- induced damage at a dose of 50 nmols but not at 10 nmols. The monoamine oxidase inhibitor nialamide (10 and 50 nmols) did not afford protection. The results suggest that quinolinic acid-induced neuronal damage can be prevented by melatonin and deprenyl, which can act as a potent free radical scavenger and can increase the activity of endogenous antioxidant enzymes. This suggests that free radical formation contributes significantly to quinolinic acid-induced damage in vivo.

   
   
   

7. The role of ultrasound in detection of stroke risk

   Full source: Journal of Computer Assisted Tomography, 1999, Vol. 23, Suppl. 1, PP S75-S81

   Stroke is the third leading cause of death in the western world and the major cause of disability among the middle aged and elderly populations. Carotid artery stenosis (vessel narrowing) is the single most important risk factor for stroke. The risk of stroke is reduced by surgery in those with high-grade stenosis. Carotid plaque structure also plays an important role; plaques that are ulcerated are associated with a higher risk of stroke. An x-ray of an artery has been the standard diagnostic tool for evaluation of carotid artery disease, but it is an invasive and costly technique that carries the risk of potentially serious complications. On the other hand, Doppler ultrasound can provide functional and anatomical information on vessel narrowing and plaque structure and is an inexpensive and noninvasive tool. Color and Spectral Doppler ultrasound are now recognized as the best screening tests for carotid artery stenosis. The recent availability of ultrasound contrast agents helps to distinguish between false and true obstructions in the artery, improves ultrasound images, and should help to reduce operator variability.
   
   

   
   

8. Neuroprotective effects of progesterone

   Full source: Journal of the Neurological Sciences, 1999, Vol. 171, Iss 1, PP 24-30

   Treatment of cerebral ischemia ( anemia due to arterial narrowing) in rodents with administration of progesterone, dissolved in dimethyl sulfoxide (DMSO), has demonstrated therapeutic efficacy. A study tested whether IV administration of progesterone 2 hours after the onset of blockage of the cerebral artery provides therapeutic benefit for the treatment of stroke. The results indicated that IV administration of progesterone at a dose of 8 mg/kg significantly reduces the volume of cerebral infarction (sudden insufficiency of blood supply due to clotting) and significantly improves outcome. However, treatment with a dose of 4 mg/kg or 32 mg/kg of progesterone failed to provide any therapeutic benefit. Thus, progesterone may have important therapeutic benefits for the treatment of stroke.

   
   

9. Protective effect of aminoguanidine on the liver

   Full source: Life Sciences, 2000, Vol. 66; Iss 3, PP 265-270

   A study evaluated the effect of aminoguanidine (AG) on carbon tetrachloride (CC14)-induced liver toxicity in rodents. Treatment with CC14 resulted in damage to the liver, increase in blood aminotransferase (enzyme) and rise in lipid peroxides level 24 hours after CC14 administration. Pretreatment of rodents with AG 30 minutes before CC14, was found to protect rodents from the CC14- induced liver toxicity. This protection was evident from the significant reduction in blood aminotransaferase, inhibition of lipid peroxidation and prevention of CC14-induced liver death. Aminoguanidine is also a relatively specific inhibitor of inducible nitric oxide synthase. This enzyme plays significant roles in blood vessel widening, kidney function, and vascular tone. It is induced by endotoxins in liver cells. Aminoguanidine did not, however, inhibit the in vitro lipid peroxidation. The results suggest a potential role of nitric oxide as an important mediator of carbon tetrachloride-induced liver toxicity.