A. Al-Bader

SELENIUM AND LIVER CIRRHOSIS

Effects of selenium deficiency, induced by thioacetamide, were investigated in rats. Thioacetamide (0.3 g/L) given in drinking water, as expected, caused a significant loss of selenium from the liver. It was accompanied by liver cirrhosis and a significant increase in the liver weight as well as liver to body weight ratio. A significant loss of selenium from spleen was also accompanied by an increase in its weight. Weights of lungs, testis and kidney, however, were not affected by thioacetamide and there was no change in their selenium content. Plasma levels of selenium were significantly reduced in the thioacetamide treated group. All these changes were confirmed to be due to selenium deficiency caused by thioacetamide, as supplementation with selenium reversed these changes. The mode of action of selenium is unknown but may involve anti-oxidant defense mechanisms.

Effect of green tea in the prevention and reversal of fasting-induced intestinal mucosal damage

OBJECTIVE Epidemiologic studies have suggested that high consumption of green tea protects against the development of chronic active gastritis and decreases the risk of stomach cancer. The effect of green tea on the intestinal mucosa was not studied previously, so we examined the effects of green tea on the intestinal mucosa of fasting rats in a controlled experimental setting. METHODS Two sets of experiments were performed. In the recovery set, rats were fasted for 3 d, after which they were allowed free access to water, black tea, green tea, or vitamin E for 7 d. On day 8, the animals were killed, and small bowels were removed for histologic examination. In the pretreatment set, rats were allowed a normal diet, but the water supply was replaced with green tea, black tea, or vitamin E for 14 d. They were subsequently fasted for 3 d. On day 4, the rats were killed, and small bowels were removed for histologic examination. RESULTS In the recovery set, fasting for 3 d caused shortening of villi, atrophy, and fragmentation of mucosal villous architecture, with a significant (P < 0.0001) reduction in the length and surface area of the villi. Ingestion of green tea and, to a lesser extent, vitamin E for 7 d helped in the recovery of villi to normal. In the pretreatment set, drinking green tea, black tea, or vitamin E for 14 d before fasting protected intestinal mucosa from damage. CONCLUSION The mucosal and villous atrophy induced by fasting was reverted to normal by the ingestion of green tea and, to a lesser extent, vitamin E. Black tea ingestion had no effect. In addition, ingestion of black tea, green tea, and vitamin E before fasting protected the intestinal mucosa against atrophy.

Cholangiocarcinoma and liver cirrhosis in relation to changes due to thioacetamide

Different doses of thioacetamide (0.05, 0.1 and 0.15%) were used to induce liver cirrhosis in Wistar rats. Thioacetamide at 0.5% caused cirrhosis by the twelfth week of treatment. A severe bile duct proliferation and cholangiocarcinoma was seen at longer intervals. Animals treated with higher doses (0.1 and 0.15%) of thioacetamide developed more severe intense degenerative changes in the liver and died in the twelfth and eighth week respectively. The serum and tissue contents of Zn and Cu changed in a characteristic fashion that was consistent with the severity of the liver damage. Serum Zn and Cu concentrations were at their lowest in the animals that developed severe degenerative liver and died at higher dose (0.15%) of thioacetamide.This study indicates that treatment of rats with 0.05% thiocetamide is more effective and appropriate for the induction of liver cirrhosis. Continued administration of the drug at this dosage led to the development of further changes in the liver. This model may be suitable for studying these long term changes that occur in the liver and lead to cirrhosis. Events that precede the development of severe bile duct proliferation and cholangiocarcinoma may also be studied.

Serum changes in trace elements during thyroid cancers

The objective was to examine changes in trace elements due to thyroid cancer in humans. Serum levels and tissue contents of trace elements (Zn, Cu, Mn, Mg, Fe and Se) were measured in 43 patients with thyroid cancer before and 4 days after surgery were compared to normal values. The serum levels of zinc in cancer patients were lower than those of normal subjects. Surgical removal of the cancer resulted in the restoration of these levels. Although serum Cu levels in patients were not different from normal, but post-operatively these levels rose significantly (p < 0.001). Levels of Fe, Mg and Mn were significantly lower (p < 0.001) post-operatively. There was no significant change in Serum Se levels. The thyroid tissue contents of these trace elements did not show a difference between the normal (Juxta-tumor) thyroid tissue and the cancerous lesion. Out of the six trace elements examined, the decrease of serum levels of zinc in cancer patients may be linked to the disease condition. It is suggested that this change: (a) may be used to demonstrate successful cancer surgery and (b) may have implications for a long-term follow-up of thyroid cancer patients.

Serum zinc and copper concentrations in pregnant women from Kuwait

Although it is well known that plasma concentrations of certain essential trace elements such as zinc and copper are altered during pregnancy, such data are not available for women in Kuwait. We analyzed the plasma of 120 pregnant Kuwaiti women aged 19–40 years (mean age 27 ± 5.7 years) and 40 controls of similar age. Blood samples from the pregnant women were collected during the first (n = 40), second (n = 40), and third (n = 40) trimesters. The trace elements were analyzed by flame as well as graphite furnace atomic absorption spectrophotometry. The results indicated that the levels of zinc decreased steadily and significantly from the first trimester through the third trimester, with a reciprocal increase in the level of copper during the same period. Thus, the copper/zinc ratio increased steadily from first trimester to the third trimester (3.5 ± 1.8, 3.9 ± 1.1, and 5.8 ± 3.3, respectively) compared to the control ratio, which was 2 ± 1. The maximum decrease in zinc and maximum increase in copper were observed during weeks (35–36) of pregnancy. Such changes could be due to the requirements of the fetus for growth. J. Trace Elem. Exp. Med. 10:209–215, 1997.

Expression of E-cadherin in human colorectal cancer

AIM To investigate the expression of E-cadherin, a calcium-dependent cell-cell adhesion molecule in colorectal carcinoma. Antibodies to E-Cadherin were used to establish the association of their expression with the clinicopathological characteristics of this disease using immunohistochemical methods. METHODS Immunohistochemical analysis for E-cadherin was carried out in formalin-fixed, paraffin-embedded sections of neoplastic colorectal tissues and non-neoplastic ones adjacent to the lesion from 49 patients who underwent surgery, by the standard peroxidase-antiperoxidase method. Expression of this antigen in normal and malignant epithelium and stromal cells was compared. RESULTS Both neoplastic and normal tissues showed expression of E-cadherin. There was, however, higher expression of E-cadherin in epithelial cells in both tumour and normal tissues than stromal cells. The percentage of expression in epithelial cells of well-differentiated tumours was significantly higher than moderately differentiated tumours. Loss of normal membranous expression and the presence of cytoplasmic and mixed staining were found frequently in tumour tissues (p = 0.004). This loss of membranous expression, however, did not correlate with Dukes staging, tumour grade, sex, size or site of the tumour. CONCLUSION This study suggests that the lower expression of E-cadherin in less differentiated tumours may explain their aggressive nature, although loss of membranous expression was not significantly correlated to Dukes staging, tumour grade, sex, size and site of tumour.

Thioacetamide induced changes in trace elements and kidney damage

Toxic effects of thioacetamide on the rat kidney were investigated by conducting trace element analysis as well as histological and histochemical assessments, at 0, 3, 6, and 12 weeks posttreatment durations. A decrease in serum as well as tissue copper was noted at 3, 6, and 12 weeks, whereas the decrease in kidney zinc was a delayed event occurring only at 12 weeks. Copper/zinc ratio was also decreased in serum as well as kidney. Serum selenium was higher, whereas kidney selenium was decreased. Manganese was the only element that showed increase in serum as well as kidneys in response to this acetamide treatment. First structural injury in the kidneys became apparent at 6 weeks, and it was represented by congestion of the glomeruli and focal mesengial cell proliferation. Structure of proximal and distal convoluted tubules was unchanged up to this point. At 12 weeks, there was an increased deposition of the collagen in the renal medulla and fibrin in the cortex. PAS positive material increased in the glomeruli and basement membrane of the tubules. Study shows that changes in trace elements precede structural damage in the kidney. Further studies are needed to establish the cause and effect relationship between these two pathologies in the kidney. J. Trace Elem. Exp. Med. 12:1–14, 1999.

Induction of prematurely condensed chromosomes by mitoplasts.

The objective of this study was to obtain pure prematurely condensed chromosomes (PCC) by a fusion between mitoplasts and interphase G1 cells. The stabilization of mitoplasts with spermine (25 microM) and a modification of the Sendai virus-mediated fusion enabled us to obtain pure PCC without contaminating mitotic chromosomes. This study clearly suggests that the factors for premature chromosome condensation induction are present in the cytoplasm of the mitotic cells. Pure PCC obtained by this method may help us to understand the nature of the factors initiating chromosome condensation and cell division.

Expression of CD44s in human colorectal cancer

CD44s is a cell adhesion molecule, which belongs to the family of hyaluronan binding proteins. Anti-body to CD44s is used to establish the association of its expression with the clinicopathological characteristics of colorectal cancer using immunohistochemical methods. The aim of this study is to investigate the expression of the standard form of CD44 (CD44s) in colorectal cancer tissues as compared to adjacent normal colonic tissues. Furthermore, the level of expression of CD44s in colorectal cancer tissues was correlated with the degree of histological differentiation, Duke’s classification, sex, size and site of the tumor. Immunohistochemical analysis for CD44s was carried out in 49 paraffin-fixed sections of neoplastic colorectal tissues and nonneoplastic ones adjacent to the lesion, by the standard peroxidase-antiperoxidase method. Expression of these antigens were compared in normal and malignant epithelium and stromal cells. The results show that the level of CD44s in the epithelial and stromal cells was significantly higher in the colorectal cancer tissues than the normal ones. However, there was no association between the percentages of expressions of CD44s and the degree of histological differentiation, Duke’s classification, sex or size of the tumor. There was however, a significantly higher expression of CD44s in the epithelium of rectal cancer than that of colonic cancer. This study indicates that the expression of CD44s is significantly higher in colorectal cancer tissues. However, further studies are required to understand its role in tumor progression and metastasis of this disease.

Serum Values of Copper, Zinc and Selenium in Adults Resident in Kuwait

Objective: The populations of Kuwait and other Arabian Gulf States are very heterogeneous. Expatriates with different dietary habits constitute approximately 60% of the Kuwaiti population. The aim of this study was to establish a reference range of trace element levels in the serum of the normal population in Kuwait. Method: A total of 379 healthy males (n = 262) and females (n = 117) of various nationalities living in the State of Kuwait were studied. The serum concentrations of zinc (Zn), copper (Cu) and selenium (Se) were measured and the copper/zinc (Cu/Zn) ratio was calculated. Results: The study established the serum Zn, Cu and Se levels in the studied population. The results showed that there was no significant difference in the serum levels of these elements among the different nationalities tested. A significantly higher serum Cu level and Cu/Zn ratio were seen in females. Conclusion: These findings can form the basis and reference for any future studies on trace elements in different pathologic conditions in the Arabian Gulf region.