Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction

Melatonin is uncommonly effective in reducing oxidative stress under a remarkably large number of circumstances. It achieves this action via a variety of means: direct detoxification of reactive oxygen and reactive nitrogen species and indirectly by stimulating antioxidant enzymes while suppressing the activity of pro-oxidant enzymes. In addition to these well-described actions, melatonin also reportedly chelates transition metals, which are involved in the Fenton/Haber-Weiss reactions; in doing so, melatonin reduces the formation of the devastatingly toxic hydroxyl radical resulting in the reduction of oxidative stress. Melatonin's ubiquitous but unequal intracellular distribution, including its high concentrations in mitochondria, likely aid in its capacity to resist oxidative stress and cellular apoptosis. There is credible evidence to suggest that melatonin should be classified as a mitochondria-targeted antioxidant. Melatonin's capacity to prevent oxidative damage and the associated physiological debilitation is well documented in numerous experimental ischemia/reperfusion (hypoxia/reoxygenation) studies especially in the brain (stroke) and in the heart (heart attack). Melatonin, via its antiradical mechanisms, also reduces the toxicity of noxious prescription drugs and of methamphetamine, a drug of abuse. Experimental findings also indicate that melatonin renders treatment-resistant cancers sensitive to various therapeutic agents and may be useful, due to its multiple antioxidant actions, in especially delaying and perhaps treating a variety of age-related diseases and dehumanizing conditions. Melatonin has been effectively used to combat oxidative stress, inflammation and cellular apoptosis and to restore tissue function in a number of human trials; its efficacy supports its more extensive use in a wider variety of human studies. The uncommonly high-safety profile of melatonin also bolsters this conclusion. It is the current feeling of the authors that, in view of the widely diverse beneficial functions that have been reported for melatonin, these may be merely epiphenomena of the more fundamental, yet-to-be identified basic action(s) of this ancient molecule.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jpi.12360

Melatonin as an antioxidant: under promises but over delivers.

Two of the most important prognostic indicators for breast cancer are tumor size and extent of axillary lymph node involvement. Data on 24,740 cases recorded in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute were used to evaluate the breast cancer survival experience in a representative sample of women from the United States. Actuarial (life table) methods were used to investigate the 5-year relative survival rates in cases with known operative/pathologic axillary lymph node status and primary tumor diameter. Survival rates varied from 45.5% for tumor diameters equal to or greater than 5 cm with positive axillary nodes to 96.3% for tumors less than 2 cm and with no involved nodes. The relation between tumor size and lymph node status was investigated in detail. Tumor diameter and lymph node status were found to act as independent but additive prognostic indicators. As tumor size increased, survival decreased regardless of lymph node status; and as lymph node involvement increased, survival status also decreased regardless of tumor size. A linear relation was found between tumor diameter and the percent of cases with positive lymph node involvement. The results of our analyses suggest that disease progression to distant sites does not occur exclusively via the axillary lymph nodes, but rather that lymph node status serves as an indicator of the tumor's ability to spread.

Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases

Peutz-Jeghers syndrome (PJS, MIM175200) is an autosomal dominant condition defined by the development of characteristic polyps throughout the gastrointestinal tract and mucocutaneous pigmentation. The majority of patients that meet the clinical diagnostic criteria have a causative mutation in the STK11 gene, which is located at 19p13.3. The cancer risks in this condition are substantial, particularly for breast and gastrointestinal cancer, although ascertainment and publication bias may have led to overestimates in some publications. Current surveillance protocols are controversial and not evidence-based, due to the relative rarity of the condition. Initially, endoscopies are more likely to be done to detect polyps that may be a risk for future intussusception or obstruction rather than cancers, but surveillance for the various cancers for which these patients are susceptible is an important part of their later management. This review assesses the current literature on the clinical features and management of the condition, genotype-phenotype studies, and suggested guidelines for surveillance and management of individuals with PJS. The proposed guidelines contained in this article have been produced as a consensus statement on behalf of a group of European experts who met in Mallorca in 2007 and who have produced guidelines on the clinical management of Lynch syndrome and familial adenomatous polyposis.

/pdf/peutz-jeghers-syndrome-a-systematic-review-and-56s1mqly6r.pdf

Peutz–Jeghers syndrome: a systematic review and recommendations for management

BACKGROUND & AIMS
A cascade of precursor lesions (eg, atrophic gastritis, intestinal metaplasia, and dysplasia) precedes most gastric adenocarcinomas. Quantification of gastric cancer risk in patients with premalignant gastric lesions is unclear, however. Consequently, endoscopic surveillance is controversial, especially in Western populations.


METHODS
To analyze current surveillance practice and gastric cancer risk in patients with premalignant gastric lesions, all patients with a first diagnosis between 1991 and 2004 were identified in the Dutch nationwide histopathology registry (PALGA); follow-up data were evaluated until December 2005.


RESULTS
In total, 22,365 (24%) patients were diagnosed with atrophic gastritis, 61,707 (67%) with intestinal metaplasia, 7616 (8%) with mild-to-moderate dysplasia, and 562 (0.6%) with severe dysplasia. Patients with a diagnosis of atrophic gastritis, intestinal metaplasia, or mild-to-moderate dysplasia received re-evaluation in 26%, 28%, and 38% of cases, respectively, compared with 61% after a diagnosis of severe dysplasia (P < .001). The annual incidence of gastric cancer was 0.1% for patients with atrophic gastritis, 0.25% for intestinal metaplasia, 0.6% for mild-to-moderate dysplasia, and 6% for severe dysplasia within 5 years after diagnosis. Risk factors for gastric cancer development were increasing severity of premalignant gastric lesions at initial diagnosis (eg, severe dysplasia, hazard ratio 40.14, 95% confidence interval 32.2-50.1), increased age (eg, 75-84 years, hazard ratio 3.75, 95% confidence interval 2.8-5.1), and male gender (hazard ratio 1.50, 95% CI 1.3-1.7).


CONCLUSIONS
Patients with premalignant gastric lesions are at considerable risk of gastric cancer. As current surveillance of these patients is inconsistent with their cancer risk, development of guidelines is indicated.

Gastric cancer risk in patients with premalignant gastric lesions

OBJECTIVE. The aim of this study was to investigate dynamic contrast-enhanced MRI (DCE-MRI) for the noninvasive measurement of bladder cancer angiogenesis by correlation with microvessel density, histologic grade, and tumor staging, and to predict the outcome of local recurrence.MATERIALS AND METHODS. Twenty-four patients with bladder cancer were examined using DCE-MRI. Hemodynamic parameters obtained by DCE-MRI included peak time enhancement in the first minute (Emax/1) after contrast administration, second minute (Emax/2), third minute (Emax/3), fourth minute (Emax/4), and fifth minute (Emax/5), and the steepest slope. Microvessel density was identified by immunostaining of endothelial cells using FVIII-related antigen. The Mann-Whitney U test, multivariate discriminant analysis, Spearman's correlation coefficient, and analysis of variance were used for statistical analysis.RESULTS. Correlation was seen between DCE-MRI parameters (Emax/1 and steepest slope) and microvessel density (p < 0.05). Emax/1 and...

https://www.ajronline.org/doi/pdfplus/10.2214/AJR.08.1332

Value of dynamic contrast-enhanced MRI and correlation with tumor angiogenesis in bladder cancer.

Protective effect of melatonin on contractile activity and oxidative injury induced by ischemia and reperfusion of rat ileum.

Nitrate incorporation in humans takes place via
drinking water and food. The water used for drinking and
cooking in the goitrous areas is high in nitrate content. The
aim of the present study was to evaluate both chronic
effects and the dose–response relationship of nitrate on
thyroid functions. A total of rats were divided into 5 work
groups and sodium nitrate was added to their drinking
water in different concentrations (0, 50, 100, 250 and 500
mg/l) over a 30–week period. The radioiodine uptake of
thyroid was decreased in the 50 mg/l nitrate group, whereas
it was increased in the 250 and 500 mg/l nitrate groups
as compared to control. All hormones of thyroid gland
except total thyroxine and thyroid–stimulating hormone
were decreased in the 50, 250 and 500 mg/l nitrate groups.
However, the level of total thyroxin was increased in the
100 mg/l nitrate group. Thyroid gland weights were
increased in all experimental groups. Histomorphological
changes were observed in the 250 and 500 mg/l nitrate
groups. These findings suggest that nitrate impairs thyroid
function involving the hypothalamo–hypophysio–thyroid
axis. This observation could contribute to the current discussion
about the acceptable daily intake of nitrate, as well
as drinking water nitrate standard safety margins.

The effects of taking chronic nitrate by drinking water on thyroid functions and morphology.

AIM: To investigate whether antioxidants vitamin E and C can retard development of hepatic fibrosis in the biliary-obstructed rats.

METHODS: Fifty Wistar albino rats were randomly assigned to 5 groups (10 rats in each). Bile duct was ligated in 40 rats and they were treated as follows: group vitC, vitamin C 10 mg/kg sc daily; group vitE, vitamin E 15 mg/kg sc daily; group vitEC, both of the vitamins; bile duct-ligated (BDL, control) group, physiological saline sc. The fifth group was assigned to sham operation. At the end of fourth week, the rats were decapitated, and hepatic tissue biochemical collagen content and collagen surface area were measured. Hepatic tissue specimens were histopathologically evaluated according to Scheuer system. Serum hyaluronate levels were measured by ELISA method.

RESULTS: Despite being higher than sham group, hepatic collagen level was significantly decreased in each of the vitC, vitE and vitEC groups (32.7 ± 1.2, 33.8 ± 2.9, 36.7 ± 0.5 μg collagen/mg protein, respectively) compared to BDL (48.3 ± 0.6 mg collagen/g protein) (P < 0.001 for each vitamin group). Each isolated vitamin C, isolated vitamin E and combined vitamin E/C supplementation prevented the increase in hepatic collagen surface density (7.0% ± 1.1%, 6.2% ± 1.7%, 12.3% ± 2.0%, respectively) compared to BDL (17.4% ± 5.6%) (P < 0.05 for each). The same beneficial effect of vitamin C, vitamin E and combined vitamin E/C treatment was also observed on the decrease of serum hyaluronate levels compared to BDL group (P < 0.001). The relative liver and spleen weights, serum transaminases, cholestatic enzymes, bilirubins and histopathological inflammation scores were not different between the antioxidant treatment groups and the control. However, fibrosis staging scores were obviously reduced only in the vitamin E/C combination group (vit EC: 2.4 ± 0.8 vs BDL: 3.1 ± 0.7; P < 0.05).

CONCLUSION: Each antioxidant vitamin E, vitamin C and their combination retard hepatic fibrosis in biliary-obstructed rats. Oxidative stress may play a role in the pathogenesis of hepatic fibrosis in secondary biliary cirrhosis.

Antioxidants vitamin E and C attenuate hepatic fibrosis in biliary-obstructed rats.

https://www.fertstert.org/article/S0015-0282(03)02230-1/pdf

Semsi Altaner

Papers

Value of dynamic contrast-enhanced MRI and correlation with tumor angiogenesis in bladder cancer.

Protective effect of melatonin on contractile activity and oxidative injury induced by ischemia and reperfusion of rat ileum.

The effects of taking chronic nitrate by drinking water on thyroid functions and morphology.

Antioxidants vitamin E and C attenuate hepatic fibrosis in biliary-obstructed rats.

Comparison of the effects of letrozole and clomiphene citrate on ovarian follicles, endometrium, and hormone levels in the rat