Signal Averaging of the Surface QRS Complex: Practical Applications

Signal-Averaged ECG. Signal averaging of the surface QRS complex has been used in recent years to detect electrical signals of small amplitude not otherwise evident on the surface ECG. The technique enables detection of low-amplitude signals in the terminal portion of the QRS complex and the ST segment. These low-amplitude signals termed late potentials (LPs) have been correlated with the presence of fragmented electrical activity recorded from endocardial and epicardial sites due to inhomogeneous propagation of conduction in scarred myocardium. Recent studies have supported the value of the signal-averaged ECG for risk stratification postmyocardial infarction, in the management of patients with syncope and patients with sustained ventricular tachycardia (VT), and survivors of cardiac arrest.     

Antimicrobial Effects of the Stem Bark Extracts of Parkia Biglobosa (Jacq.) Benth. on Shigellae

Total and hydroalcoholic extracts of the stem barks of Parkia biglobosa (Jacq) Benth. (Mimosaceae) were tested on strains belonging to three species of Shigellae: S. dysenteriae, S. flexneri and S. boydii collected from hospitals in Ouagadougou, Burkina Faso. The results showed that both extracts were active against Shigellae. The hydroalcoholic extract was more active than the decoction (aqueous one) prescribed by the traditional healer. Both extracts were particularly effective against S. dysenteriae, the most virulent of the three pathogenic species. The effects of the extracts have been compared to that of gentamicin. The phytochemical screening on the extracts revealed the presence of sterols, triterpenes, polyphenolic compounds including tanins, flavonoids, coumarins, anthocyanidins. Other components are saponosides and reducing sugars.     

Apoptosis and proliferation under conditions of deoxynucleotide pool imbalance in liver of folate/methyl deficient rats

Weanling male F344 rats were fed either a semi-purified diet low in methionine and lacking in choline and folic acid (folate/methyl deficient) or a supplemented control diet for periods of 2, 5, 7 days, 3 weeks, and 9 weeks. Two days after initiating the folate/methyl deficient diet in weanling F344 rats, the incidence of apoptotic bodies, identified by in situ end-labeling of 3'-OH DNA strand breaks, was significantly increased in liver sections from the deficient rats. Apoptotic cell death was confirmed biochemically by an increase in nuclear Ca2+/Mg2+-dependent endonuclease activity that paralleled the increase in apoptotic bodies over the 9-week feeding period. There was no morphologic evidence of necrotic foci or necrosis-associated inflammatory response over the 9-week period. Confirming that cell turnover is chronically elevated in this model, the increase in apoptotic rate was accompanied by a sustained increase in the mitotic index (MI). The DNA repair-associated enzyme, poly(ADPribose) polymerase (PARP), was similarly elevated and was associated with significant decreases in the substrate for ADPribose polymer synthesis, nicotinamide adenine dinucleotide (NAD). Because folate metabolites are essential for de novo purine and thymidine biosynthesis, prolonged deficiency in folic acid can induce an imbalance in the deoxynucleotide precursors for DNA replication/repair and negatively affect the fidelity of DNA synthesis. Using an HPLC method, hepatic deoxyuridine triphosphate (dUTP) levels were increased at 3 and 9 weeks after initiation of the deficient diet and levels of thymidine triphosphate (dTTP) were reduced. An increase in dUTP/ dTTP ratio is consistent with a block in folate-dependent de novo thymidylate biosynthesis and may predispose to uracil misincorporation and DNA repair-related DNA strand breaks.      

Ferroportin and hepcidin: a new hope in diagnosis,prognosis, and therapy for breast cancer

Breast cancer is the most prevalent malignancy in women. The success of breast cancer treatment relies on the ability to detect the disease and correct molecular abnormalities at an early stage of disease development. A recent article describes a marked decrease in the levels of ferroportin in breast cancer. More importantly, the presented results demonstrate convincingly the incredible diagnostic and prognostic value of ferroportin and hepcidin gene expression in breast cancer and suggest that determination of these two molecular markers may be used as guidance toward individualized therapy for breast cancer patients.     

Epigenetic events in tumorigenesis: putting the pieces together

The development of cancer is a complex multifactorial process traditionally viewed as the stepwise accumulation of genetic alterations. However, recent advances in field of cancer research have established that all major human cancers, in addition to a large number of genetic alterations, exhibit prominent epigenetic abnormalities. This review presents current evidence that epigenetic alterations are not only key features of cancer cells, but they also may be key events in the initiation of carcinogenesis. The early appearance of cancer-linked epigenetic changes that are similar to those found in malignant cells provides a unique opportunity to use them as biomarkers in early cancer detection, indicators of carcinogenic exposure, and in the assessment of the carcinogenic potential of environmental chemical and physical agents.     

Radiation-induced molecular changes in rat mammary tissue: possible implications for radiation-induced carcinogenesis

PURPOSE: Ionizing radiation is a potent mammary gland carcinogen, yet the exact molecular etiology of radiation-induced breast cancer remains unknown. MATERIALS AND METHODS: Our study utilized a rat model of breast carcinogenesis to analyse the molecular and epigenetic changes induced in mammary gland tissue upon exposure to ionizing radiation (IR). Using a methylation-sensitive cytosine extension assay we studied the IR-induced changes in DNA methylation. In parallel, we analysed the expression of proteins involved in DNA methylation, DNA repair and cell proliferation control. Molecular changes were related to cellular proliferation and apoptosis. RESULTS: We found that IR led to a loss of genomic cytosine methylation in the exposed mammary tissue. Global DNA hypomethylation was paralleled by reduction in the levels of maintenance (DNMT1) and de novo (DNMT3a and 3b) DNA methyltransferases and methyl-binding protein MeCP2. The observed DNA hypomethylation was linked, at least in part, to activation of DNA repair processes. Concurrently, we observed increased levels of phosphorylated extracellular signal-regulated kinase (p-ERK1/2), phosphorylated AKT kinase (p-AKT), cyclin D1 and proliferating cells nuclear antigen (PCNA) proteins, suggesting IR alters intra-cellular signaling and cell cycle control mechanisms in mammary tissue. We also noted a significant induction of apoptosis in the exposed tissue 6 hours after irradiation. The observed apoptosis levels were paralleled by the slight elevation of cellular proliferation. CONCLUSIONS: We have demonstrated that a single exposure to 5 Gy of X rays leads to noticeable epigenetic changes in the rat mammary gland that occurred in the context of activation of DNA damage repair and alterations in the pro-survival growth-stimulatory cellular signaling pathways. The possible cellular repercussions of the observed changes in relationship to breast carcinogenesis are discussed.     

Determination of the DDE and PCB contents of peregrine Falcon eggs: A comparison of whole egg measurements and estimates derived from eggshell membranes

A method using eggshell membranes to determine egg content levels of DDE and polychlorobiphenyls (PCBs), two of the most ubiquitous environmental contaminants, has been validated. A comparison was made between the residue levels determined from the egg contents of 40 Peregrine Falcon (Falco peregrinus) eggs and from hexanesoluble extracts of the dried eggshell membranes. The results confirm the use of museum eggshells for estimations of DDE and PCB levels of the original egg contents. This method should be valid for other lipophilic compounds. The data generated are of use not only to determine the records of past contamination, but may be expected to provide useful information on patterns of contamination encountered in different geographical areas. The membrane extraction technique allows pollutant levels to be measured without removing viable material from endangered species.     

Dynamics of the selenium content and selenium-dependent glutathione peroxidase activity in mice and rats with transplantable tumors

Guerin's adenocarcinoma in rats and Ehrlich ascites tumor in mice involved loss of selenium in visceral organs matched by its simultaneous accumulation in tumor tissue. The activity of selenium-dependent glutathione peroxidase was found to increase. The said changes seem to be due to antioxidizing properties of selenium.