Protective Effects of Ginger (Zingiber officinale) Extract against Diabetes-Induced Heart Abnormality in Rats.

BACKGROUND: Diabetic cardiomyopathy is an important causal factor in morbidity and mortality among diabetic patients, and currently, no effective means are available to reverse its pathological progress. The purpose of the present study was to investigate the effect of ginger extract on apolipoproteins (apo) A and B, hyperhomocysteinemia, cathepsin G and leptin changes, as well as cardiac fibrosis and heart muscle cell proliferation under hyperglycemic conditions in vivo. METHODS: Twenty-four male Wistar rats were divided into three groups, namely: control, non-treated diabetic, and ginger extract-treated diabetic groups. The ginger extract-treated diabetic group received a 50 mg daily dose of ginger extract intragastrically for 6 weeks. RESULTS: The results revealed concurrent significant increases in plasma C-reactive protein (CRP), homocysteine (Hcy), cathepsin G and apoB levels and decreases in apoA and leptin levels in the non-treated diabetic group compared to the control group. Moreover, heart structural changes, including fibrosis and heart muscle cell proliferation, were observed in non-treated diabetic rats compared to the control rats. Significant amelioration of changes in the heart structure together with restoration of the elevated levels of Hcy and CRP, leptin, cathepsin G, and apoA and B were found in the ginger extract-treated diabetic group compared to the non-treated diabetic group. CONCLUSION: The findings indicated that ginger extract significantly reduces heart structural abnormalities in diabetic rats and that these effects might be associated with improvements in serum apo, leptin, cathepsin G, and Hcy levels and with the antioxidant properties of ginger extract.

The protective effect of vitamin E against prenatal and early postnatal ethanol treatment-induced heart abnormality in rats: a 3-month follow-up study.

Ethanol consumption during pregnancy is associated with fetal heart malformation. However, the underlying mechanism of prenatal ethanol exposure causing heart malfunction is not well known. The current study examined the effect of prenatal and early postnatal ethanol consumption on heart abnormality resulting from oxidative and inflammatory stress. It was also intended to find out whether vitamin E inhibits the abnormality induced by ethanol in rats' heart tissue. Pregnant Wistar rats received ethanol with/without vitamin E from the seventh day of gestation (GD7) throughout lactation. The proliferation in heart muscle cells and coronary smooth muscle cells, protein carbonyl, IL-6, TNF-α, homocysteine levels, also lipid profile in heart and plasma of male pups were measured at the end of lactation (PN 21) and 90 days after birth (PN 90). The results indicated proliferation of heart muscle and coronary smooth muscle cells along with heart structural alteration, protein oxidation, lipid peroxidation, inflammatory reaction, and hyperhomocysteinemia in offspring after 21 and 90 days of birth compared with the controls. Vitamin E treatment significantly decreased cell proliferation and heart structural alteration, compared with the group treated by ethanol alone. Furthermore, it reduced the elevation of protein carbonyl, lipid peroxidation, and increased inflammatory proteins to levels as those of the controls. These findings strongly support the idea that ethanol intake by dams during pregnancy and early postnatal days induces heart abnormality mediated by oxidative stress and inflammatory reactions, and that these effects can be alleviated by using vitamin E as an antioxidant and anti-inflammatory molecule.

The Protective Effect of Vitamin E on Morphological and Biochemical Alteration Induced by Pre and Postnatal Ethanol Administration in the Testis of Male Rat Offspring: A Three Months Follow-up Study.

BACKGROUND: Dysmorphology and dysfunction caused by prenatal ethanol consumption in different organs of the offspring are wellknown phenomena. The objective of the present study was to explore the antioxidant effect of vitamin E supplementation on testis damage induced by maternal ethanol consumption during pregnancy and early postnatal days. METHODS: Pregnant Wistar rats on gestation day 7 were assigned to 3 groups, namely, control, ethanol and ethanol-vitamin E groups. Ethanol-treated rats received 4.5 g/kg BW ethanol once per day from day 7 and the procedure continued through postnatal day 21. Vitamin E group received 300 mg of vitamin E and the same amount of ethanol. The male offspring from each group were anesthetized by 10% chloral hydrate (0.5 ml/kg body weight) on day 21 and 90 (n=8 offspring form each group on day 21 and day 90). The results were analyzed by one-way ANOVA. A p<0.05 was considered significant. RESULTS: The results revealed significant (p<0.05) changes in oxidative stress parameters, luteinizing hormone and follicle-stimulating hormone, as well as testis structural alteration in offspring of ethanol group after 21 and 90 days of birth as compared to the control. Significant amelioration of changes in testis structure, along with restoration of the elevated level of oxidative stress parameters were found in vitamin E-treated animals. CONCLUSION: The findings revealed that prenatal and postnatal ethanol-induced toxicity in testis was exerted through oxidative stress and implied that these effects could be alleviated by vitamin E as an antioxidant.

Ethanol promotes rat aortic vascular smooth muscle cell proliferation via increase of homocysteine and oxidized-low-density lipoprotein.

BACKGROUND: Increased levels of homocysteine and oxidized low-density lipoprotein (Ox-LDL) are considered independent risk factors for atherosclerosis. However, no previous study has examined the effects of ethanol-induced increase of homocysteine and Ox-LD on aortic vascular smooth muscle cell (VSMC) proliferation. The aim of the present study was to investigate the relationship between ethanol consumption, increase in homocysteine, Ox-LDL, and aortic VSMC proliferation in rats. METHODS AND RESULTS: To address this issue, 24 male Wistar rats were randomly divided into three groups: control, sham, and ethanol-treated. Homocysteine, Ox-LDL, lipid profile, and aortic VSMC proliferation were assessed after 42 days. The results revealed a concurrent, significant increase in homocysteine and Ox-LDL levels, lipid profile levels, and aortic VSMC proliferation in the ethanol-treated group compared with the control and sham groups. CONCLUSION: Based on these results, we conclude that ethanol apparently exerts aortic VSMC proliferation through increase in homocysteine and Ox-LDL-mediated oxidative stress, which in turn trigger proatherogenic changes in the aortic wall.

Vasoprotective effect of vitamin E: rescue of ethanol-induced atherosclerosis and inflammatory stress in rat vascular wall.

Chronic ethanol consumption increases the incidence of cardiovascular disease. The mechanisms underlying ethanol-induced susceptibility to cardiovascular disease continue to be defined. This study examines the hypothesis that chronic ethanol consumption plausibly induces vascular wall abnormalities via inflammatory reactions. In addition, it intends to find out whether vitamin E inhibits the abnormalities induced by ethanol in rats' vascular wall. Twenty four male Wistar rats were divided into three groups (n=8): Control ©, ethanol (E), and vitamin E treated ethanol (VETE) group. After 6weeks, the aortic and coronary wall changes, vascular endothelial growth factor (VEGF), alpha-1 glycoprotein and haptoglobin amounts in plasma, C-reactive protein levels(CRP), as well as the amount of aortic IL-6 were evaluated. The results revealed the elevation of polymorphonuclear (PMN) leukocyte in the vascular wall, disorganization of endothelium with ballooning of cells, proliferation of vasa-vasorum with an increase in the IL-6, CRP, as well as a decrease in VEGF and an increase in alpha-1 glycoprotein and haptoglobin in the ethanol group compared to the control group. Significant amelioration of aortic and coronary wall changes, along with the restoration of elevated level of IL6, CRP, and the decreased level of VEGF compared to that of the controls were found in vitamin E-treated animals. These findings strongly support the idea that heavy and chronic ethanol consumption initiates atherosclerosis by inflammatory stress, and that these effects can be alleviated by vitamin E as an anti-inflammatory agent.

Long-term ethanol consumption initiates atherosclerosis in rat aorta through inflammatory stress and endothelial dysfunction.

Controversy exists on whether alcohol has a direct cardioprotective effect or it provokes atherosclerosis, so the present study sought to assess the effect of chronic consumption of ethanol on the markers of endothelial function, vessel rigidity, and atherosclerosis in the aorta of rat. Male Wistar rats were selected randomly and exposed to ethanol (4.5g/kg of 20% w/v solution in saline) once per day for 6weeks. Blood pressure, hemodynamic parameters, foam cell formation, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelial-leukocyte adhesion molecule-1, and high-sensitivity C-reactive protein (CRP) were assessed in ethanol treated rats and compared with either sham or control rats. The results revealed a concurrent significant increase of adhesion molecules, CRP levels, systolic, diastolic, pulse, and dicrotic pressures as well as enhanced formation of foam cell in ethanol-treated rats. These findings implicate that long-term ethanol exposure provokes atherogenic and hemodynamic changes via significant induction of proinflammatory response, augmenting of cell adhesion molecules, stiffness in rat aorta wall and induction of foam cell formation.

Decreased blood pressure with a corresponding decrease in adhesive molecules in diabetic rats caused by vitamin E administration.

BACKGROUND: Hypertension is one of the important clinical problems of diabetic cardiovascular disease. The aim of this study was to determine the effect of vitamin E on blood pressure parameters and adhesive molecule amounts in diabetic rats. METHODS: Twenty-four male Wistar rats were divided into three groups (each of n = 8): the controls (C), non-treated diabetic (NTD), and vitamin E treated diabetic (VETD) groups. A single intraperitoneal injection of buffered streptozotocin (60 mg/kg) in cold sodium citrate (pH 4.5) was used to induce diabetes. The VETD group received 300 mg of vitamin E daily intragastrically for 6 weeks. Systolic and diastolic blood pressure, mean arterial pressure, as well as the dicrotic pressure, crest time, systolic and diastolic periods, and plasma levels of intercellular adhesion molecule-1 and E-selectin were measured after 6 weeks. RESULTS: The results revealed that there was a significant increase in systolic and diastolic blood pressures, mean arterial pressure, crest time, systolic duration, and the amount of sICAM-1 and E-selectin in diabetic rats. There was no significant difference in the heart rate or cardiac cyclic duration among the different groups. Significant improvement of blood pressure parameters as well as attenuation of the elevated ICAM-1 and E-selectin amounts was found in the vitamin E treated group. CONCLUSIONS: These findings indicate that vitamin E significantly improved blood pressure elevation in diabetic rats and that these effects could be associated with reducing adhesive molecule and antioxidant properties of vitamin E.

Synergistic effects of glutamine and ciprofloxacin in reduction of Pseudomonas aeruginosa-induced septic shock severity.

BACKGROUND: Systemic inflammatory response induced by over expressing inflammatory mediators is the main pathogenic mechanism of septic shock. Glutamine (Gln) has been demonstrated to inhibit pro-inflammatory cytokine release through enhanced heat shock protein (HSP) expression. OBJECTIVE: To assess the effect of co-administration of Gln and antibiotic ciprofloxacin in reduction of septic shock severity caused by Pseudomonas aeruginosa in mice. METHODS: Six- to eight-week old male BALB/c mice were used. At first, P. aeruginosa susceptibility to ciprofloxacin was determined. Then, 75% lethal dose (LD 75) of P. aeruginosa in a 10-day period was assessed. For determining survival rate, fifty mice were divided into 5 groups which included control (+), control (-), Gln, ciprofloxacin, and "glutamine+ciprofloxacin" group. All mice, except for control (-), were given an LD75 dose of P. aeruginosa and after 30 min each group received its special treatment: control (-) and control (+) groups received only 500λ phosphate buffer saline (PBS). Gln group received 500λ Ala-Gln, Cip group received 500λ ciprofloxacin. The Cip+Gln group received 500λ Gln and ciprofloxacin. Finally serum TNF-α, IL-10 and HSP-70 concentrations were measured and the severity of liver necrosis was examined. RESULTS: Glutamine in combination with ciprofloxacin significantly increased survival rate and serum HSP-70 and IL-10 concentration and significantly decreased serum TNF-α concentration and the liver necrosis severity in comparison to control (+) group. CONCLUSION: Gln has synergistic effects with ciprofloxacin in reduction of P. aeruginosa-induced septic shock.

Impact of triple negative phenotype on prognosis and early onset of breast cancer in Iranian females.

BACKGROUND: Breast cancer in Iranian women occurs about a decade earlier than in Western countries. This study sought to evaluate the impact of triple negative phenotype on early onset of ductal cell breast cancer and its prognosis in Iranian females. METHODS: Estrogen and progesterone receptors, Her-2 overexpression and nuclear accumulation of P53 were assessed in sixty surgically resected formalin-fixed paraffin embedded breast invasive ductal carcinomas. They were divided into triple negative and non triple negative phenotypes and impact of the phenotypes were evaluated on prognostic factors of all patients and based on menopausal status. RESULTS: The result showed that the mean age of patients with triple negative breast tumors, especially in postmenopausal group, was significantly lower than with non triple negative phenotypes. Although the latter was significantly associated with higher histological grade, it also showed a significant correlation with smaller size of tumor and a lower rate of axillary lymph node metastasis in young patients. CONCLUSION: The higher rate of breast cancer with triple negative phenotype in Iranian females is a feasible reason for the reported lower mean age of breast cancers. In premenopausal patients, triple negative phenotype reveals a positive impact on prognostic factors, but it is associated with a poorer prognosis in postmenopausal patients. Hence, a distinct ethnic profile of triple negative phenotype in Iranian females is suggested.

Endobronchial metastasis from oral fibrosarcoma 13 years after treatment of primary tumor.

Endobronchial metastasis (EBM) is uncommon and frequently is seen in renal, breast, and colorectal carcinomas. Other reported primary tumors include melanoma, sarcomas, and tumors of the uterine cervix, testis, ovary, prostate, thyroid, pancreas, and adrenal glands. With reviewing the literature, we were able to find only one report of EBM from fibrosarcoma (in Spanish). We described a 56-year-old woman with EBM of oral fibrosarcoma with local recurrence 13 years after treatment of primary tumor. We conclude that the possibility of central airway metastasis should be kept in mind if patients with a past history of malignancy present with symptoms consistent with bronchial tumors, even if there are 13 years interval. Of several mechanisms EBM, we assume direct aspiration and implantation of tumor cells to bronchus from oral cancer.

Cardioprotective effect of vitamin E: rescues of diabetes-induced cardiac malfunction, oxidative stress, and apoptosis in rat.

AIM: This study was designed to assess the effect of vitamin E on cardiac autonomic neuropathy, cardiomyocyte apoptosis, and the status of oxidative stress in the heart under hyperglycemic conditions, in vivo. METHODS: Wistar male rats (n=16) were made hyperglycemic by streptozotocin at 6 months of age. Normal Wistar rats (n=8) of the same age were used as the control group. Diabetic rats were divided into two groups, nontreated and those treated with vitamin E (300 mg/day). Stable hyperglycemic status was proved by levels of blood sugar and HbA(1c). Lipid peroxidation, protein oxidation, and cellular antioxidant defense were measured by 8-isoprotane, protein carbonyl content, and superoxide dismutase (SOD) activity, respectively. RESULTS: Cardiac complications such as autonomic neuropathy as prolonged QT interval along with significant increases in level of 8-isoprotane, protein carbonyl content, and SOD activity were observed after 6 weeks. Structural abnormality was also observed as severe induction of apoptosis in cardiomyocytes. CONCLUSION: Significant decline in apoptosis, lipid peroxidation, protein oxidation, and QT interval resulted from vitamin E administration, which strongly implies that this radical scavenger may promote a convalescing effect on diabetic cardiomyopathy through the attenuation of oxidative stress and abrogation of apoptotic signals, which was verified by restoring normal QT interval.

Recurrent laryngeal papillomatosis with bronchopulmonary spread in a 70-year-old man.

Recurrent laryngeal papillomatosis (RRLP) which is characterized by wart like growths in the larynx is a rare benign disease seen in children and young adults and a few cases are reported in old aged adults. The spread of RRLP throughout the respiratory tract occurs rarely; and involvement of the distal bronchi, bronchioles, and lung parenchyma is very rare. We report a case of tracheobronchial and pulmonary spread of RRLP in a 70-year-old man after two previous surgeries. Despite the rarity of this disease in adults, the correct diagnosis may be suggested by a characteristic combination of clinical, radiographic, and pathologic features.

The effect of post-burn local hyperthermia on the reducing burn injury: the possible role of opioids.

PURPOSE: This paper studied the effect of post-burn local hyperthermia on burn induced injury. METHODS: A second-degree burn injury was induced on the right and left flanks of Balb/c mice. Thirty-two burn wounds were divided into four groups. Opioid receptor blocking was done for groups 3 and 4 by intra-peritoneal administration of Naloxone (NLX) 30 min before the thermal injury. Local hyperthermia (45 degrees C, 30 s) was applied only for the burn wounds of groups 2 and 4. Twenty-four hours after burn injury, the burned wounds were assessed for the level of iNOS (by immunohistochemistry) and the number of hair follicles (as an indicator of tissue injury). RESULTS: The wounds that received hyperthermia (group 2) had significantly more hair follicles (p < 0.001) compared to the control wounds (group 1). There was no significant difference between the number of hair follicles and acute inflammation of group 1 and group 3 (NLX + burn). Group 4 (NLX + burn + hyperthermia) had significantly fewer hair follicles compared to group 1 (p < 0.001), group 2 (p < 0.001) and group 3 (p < 0.001). The level of iNOS in groups 1, 3 and 4 was not significantly different but significantly more than group 2 (p < 0.001, p < 0.001 and p < 0.001, respectively). CONCLUSIONS: The results showed that local hyperthermia after second degree burn decreased the tissue injury and iNOS expression. It is also concluded that endogenous opioid response may have a key role in the above mentioned effects of post-burn local hyperthermia.