Current Issue : October - December Volume : 2011 Issue Number : 4 Articles : 9 Articles
Instability of repetitive sequences originates from strand misalignment during repair or replicative DNA synthesis. To investigate the activity of reconstituted T4 replisomes across trinucleotide repeats (TNRs) during leading strand DNA synthesis, we developed a method to build replication miniforks containing a TNR unit of defined sequence and length. Each minifork consists of three strands, primer, leading strand template, and lagging strand template with a 5' single-stranded (ss) tail. Each strand is prepared independently, and the minifork is assembled by hybridization of the three strands. Using these miniforks and a minimal reconstituted T4 replisome, we show that during leading strand DNA synthesis, the dNTP concentration dictates which strand of the structure-forming 5'CAG/5'CTG repeat creates the strongest impediment to the minimal replication complex. We discuss this result in the light of the known fluctuation of dNTP concentration during the cell cycle and cell growth and the known concentration balance among individual dNTPs....
Chronic exposure to arsenic in drinking water poses a major global health concern. Populations exposed to high concentrations of arsenic-contaminated drinking water suffer serious health consequences, including alarming cancer incidence and death rates. Arsenic is biotransformed through sequential addition of methyl groups, acquired from s-adenosylmethionine (SAM). Metabolism of arsenic generates a variety of genotoxic and cytotoxic species, damaging DNA directly and indirectly, through the generation of reactive oxidative species and induction of DNA adducts, strand breaks and cross links, and inhibition of the DNA repair process itself. Since SAM is the methyl group donor used by DNA methyltransferases to maintain normal epigenetic patterns in all human cells, arsenic is also postulated to affect maintenance of normal DNA methylation patterns, chromatin structure, and genomic stability. The biological processes underlying the cancer promoting factors of arsenic metabolism, related to DNA damage and repair, will be discussed here....
DNA is continuously exposed to many different damaging agents such as environmental chemicals, UV light, ionizing radiation, and reactive cellular metabolites. DNA lesions can result in different phenotypical consequences ranging from a number of diseases, including cancer, to cellular malfunction, cell death, or aging. To counteract the deleterious effects of DNA damage, cells have developed various repair systems, including biochemical pathways responsible for the removal of single-strand lesions such as base excision repair (BER) and nucleotide excision repair (NER) or specialized polymerases temporarily taking over lesion-arrested DNA polymerases during the S phase in translesion synthesis (TLS). There are also other mechanisms of DNA repair such as homologous recombination repair (HRR), nonhomologous end-joining repair (NHEJ), or DNA damage response system (DDR). This paper reviews bioinformatics resources specialized in disseminating information about DNA repair pathways, proteins involved in repair mechanisms, damaging agents, and DNA lesions....
Dihydroartemisinin (DHA) has been shown to be efficacious and rapid in malaria parasite clearance and malaria treatment. The discovery that dihydroartemisinin has anti-cancer effects suggested that dihydroartemisinin may have other beneficial or adverse systemic effects. We investigated the effects of dihydroartemisinin on the heart of Wistar albino fats.. The effects of four dosages of oral dihydroartemisinin on the heart of Wistar albino rats were investigated. The dosages of DHA administered were 1mg/kg, 2mg/kg, 60mg/kg and 80mg/kg. In a fifth experiment, the 1mg/kg dosage of DHA was administered twice to a group of rats with a one week period of rest between the two administrations. The results of the study showed that DHA produced dose, repetition and time dependent increases in the caliber of the blood vessels of the coronary circulation. These findings suggest that dihydroartemisinin might be useful for the management of myocardial infarction, congestive heart failure, angina pectoris and other conditions involving narrowing of coronary arteries....
Drugs are known to be distributed in the body through osmotic or bulk flow of drug molecules across membranes of the cells of receptive sites. Cell surface receptors were shown to be the sites of disease infectivity and attachment of anti-infective drugs. Cell surface receptors were shown to be interconnected throughout the body of an organism. A close attention to the mechanisms of transfer of Vernonia amygdalina leaf extract and Vernonia amygdalina leaf powder from administration sites to sites of drug [extract] action has produced some new data on the subject. The mechanisms of translocation of orally and topically administered Vernonia amygdalina (VA) leaf extract and leaf powder were studied by a subject. The aqueous extract of VA was ingested orally and the aqueous, pea nut oil and ethanol extracts as well as the powder of VA leaf were administered topically through the tongue; the nostrils; the vulva; the vagina; and the skin of a subject. The mode of transfer of the Vernonia amygdalina leaf extract and powder molecules from these various sites of its oral or topical application were noted by the subject, The results of the study revealed that V. amygdalina leaf extract bound to cell surface receptors on the administration site membranes and from there was translocated to cell surface receptors on infected (or disordered) body sites by an electromotive flow of its molecules. The flow of the V. amygdalina leaf extract molecules to cell surface receptor sites at target infection sites was observed to be swift, smooth and continuous (unbroken) like the flow of an electric current and reached target sites through Cell surface receptor channels in one to two seconds. The movement of V. amygdalina leaf extract molecules round the body through the interlinked cell surface receptor networks which ramify the whole body was like a systematic progressive systematic sweeping movement and was observable on the skin with the naked eyes and occurred in a total of 2 minutes. Administered VA extract was first distributed to infected organs before it was distributed to uninfected organs and its distribution to infected organs was in the order of the severity of their infections. These findings show that VA leaf extract was distributed round the human body in 2 minutes through an electromotive flow of the extract molecules in cell surface receptor channels along the thin layer of tissue that connects cell surface receptors to each other. These findings enable the researcher to put forward a new theory of drug distribution in the body of living things through electromotive flow of drug molecules in cell surface receptor channels which link the drug administration site cell membrane cell surface receptors to the drug’s target site cell surface receptors...
Toxicity of arsenic and protective role of N-acetyl cysteine (NAC) was assessed on cardiac, renal and testicular biomarkers. Twenty four male Wistar rats were divided into 4 groups of 6 animals each and treated as follows: Group 1: sham control, 2: arsenic control (sodium arsenite @ 10 mg/kg b. wt orally for 4 wks), 3: Pre-treatment with NAC (@ 300 mg/kg orally for 2 wks) followed by sodium arsenite along with NAC (as per above doses) and 4: Sodium arsenite + NAC (as per above doses for 4 wks).. The concentration of thiobarbituric acid reacting substances (TBARS), protein carbonyls in heart, kidney and testis were significantly (p<0.05) increased, while the concentration of reduced glutathione (GSH) in heart, kidney and testis was significantly (p<0.05) reduced in group 2 as compared to control group. Groups 3 and 4 revealed improvement in the parameters in study. In conclusion, the study revealed that arsenic induces cardiac, renal and testicular toxicity by inducing oxidative stress and supplementation of NAC is beneficial in countering the adverse effects....
The article aims to provide a comparative estimation of Cerebrocurin®, Cortexin® and Cerebrolisin® neuroprotective effect on the outcome of experimental chronic alcoholism in rats. 50 Wistar rats were subjected to transient, experimental chronic alcoholism and were randomly assigned to 5 groups (n=10 each): (1) Intact, (2) Control, (3) Cerebricurin®, (4) Cortexin®, (5) Cerebrolisin®. Investigated preparations were administered during 14 days parenteraly after 30-days of violent alcoholization. Functional deficits were quantified by daily neurological examinations (Garcia et al., 1995); rats’ behavior was quantified in the test of Passive Avoidance Conditioned Response (PACR). Nitrotirosine values were measured after treatment. Against the background of chronic alcohol intoxication in rats, we have elevated indicators, nitrozile proteins in plasma and brain reflecting the activation processes of nitrozine stress in each groups. We have conducted correlation between the level of nitrotirozine in rat brain and the manifestations of neurological deficit in scores on McGrow in the control group at the end of the experiment. The most active drug was Cerebrocurin®, which demonstrated a significant reduction of nitrotirozine in plasma and especially in the brain of the rats relative vs vehicle-treated controls and normalized neurological status. This is an experimental justification for inclusion of Cerebrocurin® in the traditional model of treatment of chronic alcoholism....
Ranking one of the most critical worldwide health troubles relating to mortality, hepatocellular carcinoma (HCC) has been a grievous scourge of humanity for a long time. Despite that plentiful attempts have been made, it still remains being a great challenge for us to conquer this disease. Multiple molecular alterations can be frequently detected in the pathogenesis and development of HCC, such as members of Ras family, Bcl-2 family and tumor suppressors. Importantly, most of these alterations are responsible for disrupting the balance between cell proliferation and apoptosis, which has been generally voted as a key event closely associated with carcinogenesis. Hence, this review aims to update the current related articles and provide a further understanding about such molecular changes relevant to trigger imbalances in the regulation of apoptosis in HCC....
The neoplastic microenvironment has been recognized to play a critical role in the development of cancer. Although a large body of evidence has established the importance of the cancer microenvironment, the manners of crosstalk between it and the cancer cells still remains unclear. Emerging mechanisms of communication include microRNAs (miRNAs). miRNAs are small noncoding RNA molecules that are involved in the posttranscriptional regulation of mRNA. Both intracellular and circulating miRNAs are differentially expressed in cancer and some of these alterations have been correlated with clinical patient outcomes. The role of miRNAs in the tumor microenvironment has only recently become a focus of research, however. In this paper, we discuss the influence of miRNAs on the tumor microenvironment as it relates to cancer progression. We conclude that miRNAs are a critical component in understanding invasion and metastasis of cancer cells....
Loading....