Distribution of trace metal concentrations in paired cancerous and non-cancerous human stomach tissues.

AIM: To assess whether trace metal concentrations (which influence metabolism as both essential and non-essential elements) are increased or decreased in cancerous tissues and to understand the precise role of these metals in carcinogenesis. METHODS: Concentrations of trace metals including Cd, Ni, Cu, Zn, Fe, Mg and Ca in both cancerous and non-cancerous stomach tissue samples were determined by atomic absorption spectrometry (AAS). Tissue samples were digested using microwave energy. Slotted tube atom trap was used to improve the sensitivity of copper and cadmium in flame AAS determinations. RESULTS: From the obtained data in this study, the concentrations of nickel, copper and iron in the cancerous human stomach were found to be significantly higher than those in the non-cancerous tissues, by using t-test for the paired samples. Furthermore, the average calcium concentrations in the cancerous stomach tissue samples were found to be significantly lower than those in the non-cancerous stomach tissue samples by using t-test. Exceedingly high Zn concentrations (207-826 mg/kg) were found in two paired stomach tissue samples from both cancerous and non-cancerous parts. CONCLUSION: In contrast to the literature data for Cu and Fe, the concentrations of copper, iron and nickel in cancerous tissue samples are higher than those in the non-cancerous samples. Furthermore, the Ca levels are lower in cancerous tissue samples than in non-cancerous tissue samples.

The effects of low dose leukotriene receptor antagonist therapy on airway remodeling and cysteinyl leukotriene expression in a mouse asthma model.

Airway structural changes that occur in patients with asthma in response to persistent inflammation are termed airway remodeling. The cysteinyl leukotrienes (LTC(4), D(4) and E(4)) are known to play important roles in the pathobiology of asthma. To evaluate the effect of low dose montelukast (MK) on the development of airway remodeling using a chronic murine model of allergic airway inflammation with subepithelial fibrosis, BALB/c mice, after intraperitoneal ovalbumin (OVA) sensitization on days 0 and 14, received intranasal OVA periodically on days 14-75. MK treated mice received montelukast sodium intraperitoneally on days 26-75. The OVA sensitized/challenged mice developed an extensive eosinophil cell inflammatory response, goblet cell hyperplasia, mucus occlusion, and smooth muscle hypertrophy of the airways. In addition, in OVA sensitized/challenged mice, dense collagen deposition/fibrosis was seen throughout the lung interstitium surrounding the airways, blood vessels, and alveolar septae. The cysteinyl leukotriene 1 (CysLT1) receptor antagonist, MK significantly reduced the airway eosinophil infiltration, goblet cell hyperplasia, mucus occlusion, and lung fibrosis except airway smooth muscle hypertrophy in the OVA sensitized/challenged mice. The OVA sensitized/challenged mice had significantly increased epithelial desquamation compared with control mice. MK markedly reduced epithelial desquamation of airways in OVA/MK treated animals compared with OVA sensitized/challenged mice. MK treatment did not affect the levels of CysLT in lung tissue. Our results show that the important role of cysteinyl leukotrienes in the pathogenesis of asthma. Lower dose of CysLT1 receptor antagonism has a significant anti-inflammatory effect on allergen-induced lung inflammation and fibrosis but not airway smooth muscle hypertrophy in an animal model of asthma.

Protective role of alpha-tocopherol on retinal injury in experimental uveitis in guinea pigs.

PURPOSE: PURPOSEof the study was to determine whether alpha-tocopherol (AT) can protect the retina from oxidative damage in experimental uveitis (EU). MATERIAL AND METHODS: The eyes of 36 adult male guinea pigs were studied. The guinea pigs were divided into three groups of 12 animals each. The first group was used as control. The right eyes of groups 2 and 3 received an intravitreal injection of bovine serum albumin for EU induction. At the same time and also on the consecutive third and fifth days, group 3 received intraperitoneal AT injections. The samples were collected on the eighth day. Retinal malondialdehyde (MDA) levels and the average thickness of the inner plexiform layer were measured and the histopathology of the eyes was studied. RESULTS: The MDA level was significantly lower in the control group than in the groups 2 (p<0.01) and 3 (p<0.05). When compared with the EU group 2, there was a significant lowering of MDA in the AT injected group 3 (p<0.01). The thickness of the inner plexiform layer in the control group 1 was significantly lower than in the other groups (p<0.01). Its thickness in the group 3 supplied with AT was significantly lower than in the group 2 (p<0.01). CONCLUSIONS: The data indicate that intraperitoneal AT administration protects against EU injury in the guinea pig retina as evidenced by the reduced MDA and the thickness of retina.

Effect of vitamin E on follicular cell proliferation and expression of apoptosis-associated factors in rats with 6-N-propyl-2-thiouracil-induced goitrogenesis.

We have investigated immunohistochemically the effect of dl-alpha-tocopherol (vitamin E) on thyroid gland with 6-n-propyl-2-thiouracil (PTU)-induced hypothyroidism in rats. The animals were divided into four groups. Rats in group I were designated as control, rats in group II were treated with injections of PTU (10 mg/kg) for 15 days, rats in group III were treated with injections of PTU+vitamin E (10 mg/100 g) for 15 days. Rats in group IV were treated with injections PTU for 15 days and kept for 15 next days after cessation of PTU treatment. At the end of experiment, the animals were killed by decapitation, blood samples were obtained, thyroid tissues were collected and processed for quantitative evaluation of immunohistochemical PCNA (marker of cell proliferation), Bax (pro-apoptotic marker) and Bcl-2 (anti-apoptotic marker) staining. There was an increase in the number of PCNA-immunopositive cells in follicular epithelial cells of group II rats compared with other groups (p<0.05). After vitamin E treatment, the number of PCNA-immunopositive cells decreased (p<0.05) while the number of Bax-immunopositive cells increased (p<0.05). The number of Bcl-2-positive follicular epithelial cells of group IV rats was higher than in those of other groups (p<0.05). The results of this study indicate that hypothyroidism induces cell proliferation in the thyroid gland and vitamin E may promote involution of the gland.

Protective effects of melatonin against carbon tetrachloride-induced hepatotoxicity in rats: a light microscopic and biochemical study.

The aim of this study was to examine the protective effects of melatonin against CCl4-induced hepatotoxicity in the rat. Twenty-four male Wistar rats were divided into three groups. Group I was used as a control. Rats in group II were injected every other day with CCl4 for 1 month, whereas rats in group III were injected every other day with CCl4 and melatonin for 1 month. At the end of the experiment, all animals were killed by decapitation and blood samples were obtained. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total and conjugated bilirubin levels were determined. For histopathological evaluation, livers of all rats were removed and processed for light microscopy. All serum biochemical parameters were significantly higher in animals treated with CCl4 than in the controls. When rats injected with CCl4 were treated with melatonin, significantly reduced elevations in serum biochemical parameters were found. In liver sections of the CCl4-injected group, necrosis, fibrosis, mononuclear cell infiltration, haemorrhage, fatty degeneration and formation of regenerative nodules were observed. Additionally, apoptotic figures, microvesicular steatosis and hydropic degeneration in hepatocytes were seen in this group. In contrast, the histopathological changes observed after administration of CCl4 were lost from rats treated with CCl4 and melatonin. Except for mild hydropic degeneration of the hepatocytes, a normal lobular appearance was seen in the livers of this group. The results of our study indicate that melatonin treatment prevents CCl4-induced liver damage in rats.

Investigation of Epstein-Barr virus DNA in formalin-fixed and paraffin- embedded breast cancer tissues.

OBJECTIVE: To investigate etiological role of Epstein-Barr virus (EBV) DNA in breast cancer. MATERIALS AND METHODS: The presence of EBV DNA in 57 breast cancer tissues was investigated with a sensitive PCR assay. The breast cancer tissues were from invasive ductular (n=28), lobular (n=20) and other miscellaneous carcinomas (n=9). Tissues from normal breasts and patients with various benign breast diseases (n=55): fibrocystic disease (n=34), fibroadenoma (n=16), hyperplasia, and granulomatous mastitis (n=5), were used as control samples. RESULTS: EBV DNA was detected in 13 (23%) cancerous tissues (7 ductular, 4 lobular, 2 other carcinoma) and 19 (35%) in the control tissues. The difference between EBV presence in malignant and benign tissues was not statistically significant (p>0.05). CONCLUSION: The presence of EBV DNA was detected almost equally in both breast cancer and normal tissues, which indicates no etiological role for EBV in breast cancer. We suggest further etiological studies.

Effect of melatonin on wound healing in normal and pinealectomized rats.

Melatonin usage is increasing gradually, but reports of its effects on wound healing are inconsistent. It has been shown that the hormone is synthesized in and secreted from the gastrointestinal system independently of the pineal gland. We have investigated, by means of a comparative study on the healing of incision and anastomotic wounds, whether melatonin has an effect on wound healing independent of the pineal gland. Rats were divided in five groups (n = 10), all of which were subjected to small intestine anastomosis. The first group (control) was otherwise untreated. Exogenous melatonin was given to the rats in second group. The calvaria was opened then closed in the third group (sham operated), whereas the fourth group was pinealectomized and the fifth group were pinealectomized and then treated with melatonin. After anastomosis bursting pressures and incision wound breaking strength were measured on the 7th postoperative day, tissue hydroxyproline levels were determined, and histopathological investigation was performed. It was found that while collagen deposition and epithelization increased concurrently in incision wounds after pinealectomy, only collagen deposition increased at the anastomosis line. Exogenous melatonin decreased collagen synthesis and epithelium proliferation and had negative effects on wound healing in both normal and pinealectomized rats.

Protective effects of vitamin E forms (alpha-tocopherol, gamma-tocopherol and d-alpha-tocopherol polyethylene glycol 1000 succinate) on retinal edema during ischemia-reperfusion injury in the guinea pig retina.

PURPOSE: The purpose of this study is to provide evidence that free radical damage is a component of retinal ischemia-reperfusion (I/R) injury, and to determine whether alpha-tocopherol, gamma-tocopherol and d-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS) can protect the retina from this injury. METHODS: The right eyes of 40 male guinea pigs weighing 500-600 g were used. The animals were randomly assigned to group 1 (control), group 2 (I/R), group 3 (I/R plus alpha-tocopherol), group 4 (I/R plus gamma-tocopherol) and group 5 (I/R plus TPGS). Groups 3, 4 and 5 received four subcutaneous injections at six-hour intervals for total dosage of 800 IU/kg alpha-tocopherol, 1000 IU/kg gamma-tocopherol and 750 IU/kg TPGS, respectively. The first dose of each substance was administered 5 minutes before retinal ischemia. Retinal ischemia was induced for 90 minutes, then followed by reperfusion for 24 hours. Injections of three substances were repeated at 6, 12 and 18 hours during reperfusion. The animals were killed at 24 hours of reperfusion. Sagittal sections of 4 microm were cut and stained with hematoxylin and eosin for light microscopic evaluation. The average thickness (edema) of the inner plexiform layer for each eye was measured in sagittal sections near the optic nerve and expressed in microns. RESULTS: All the three substances showed statistically significant protection against the formation of retinal edema during ischemia-reperfusion injury. The mean thickness of the inner plexiform layer were 15.0, 25.44, 19.81, 21.38 and 20.88 microm in control, I/R, I/R plus alpha-tocopherol, I/R plus gamma-tocopherol and I/R plus TPGS groups, respectively. The results showed that the thickness of the inner plexiform layer in group 1 (control) was significantly lower than the other groups (p<0.001). The inner plexiform layer was thicker in the I/R group than with I/R plus alpha-tocopherol (p<0.001), I/R plus gamma-tocopherol (p<0.001) and I/R plus TPGS (p<0.01). The inner plexiform layer was not thicker in the I/R plus TPGS group than in the I/R plus alpha-tocopherol and I/R plus gamma-tocopherol groups. Compared to the I/R plus alpha-tocopherol group, the inner plexiform layer was significantly thicker in the I/R plus gamma-tocopherol group (p<0.01). CONCLUSIONS: The results from these experiments indicate that vitamin E forms have protective effects on the retina during retinal ischemia-reperfusion injury, but, the effects of alpha-tocopherol and TPGS appear to be much greater than that of gamma-tocopherol.

L-carnitine in experimental retinal ischemia-reperfusion injury.

The effect of L-carnitine on retinal ischemia-reperfusion injury was evaluated in guinea pigs. 90 min of pressure-induced retinal ischemia followed by 24 h of reperfusion was established in both eyes of 2 groups of animals receiving either L-carnitine (100 mg/kg repeated in 5 doses) or saline intraperitoneally. After enucleation of all the eyes, including those of a control group, malonyldialdehyde (MDA) levels and the thickness of the retinal tissue were measured in 3 groups. The mean MDA value and the tissue thickness of the L-carnitine-treated group were statistically insignificant versus the control group (p > 0.05 and p > 0.05, respectively). However, these values were significantly different in the group receiving saline versus the control group and that receiving L-carnitine (p < 0.001, p < 0.001 and p < 0.001, p < 0.001 respectively). L-Carnitine might be an alternative drug for ischemia-reperfusion injury of the retina.