scholarly journals A RELATIVE STUDY TO FIND OUT THE RISK POPULATION IN VINDHYAN REGION BY CARCINOGEN ACTIVATING AND DEACTIVATING THE GSTM1 POLYMORPHISM

2016 ◽  
Vol 4 (5) ◽  
pp. 133-138
Author(s):  
Snehlata Pandey ◽  
Pallavi Indurkar ◽  
Arvind Tripathi ◽  
Jitendra Thipathi ◽  
Sanjeev Dubey

The Glutathione S-transferase are a family of phase II isoenzymes, believed to protect cells from reactive chemical intermediates and oxidative stress, resulting from a wide range of electrophilic xenobiotics (Example-PAH) and endogenous intermediates. Inheritance of null (gene deletion) alleles of the GSTM1 (chromosome 1p 13.3) genes is common in the population varies by ethnicity and is associated with the loss of enzymatic activity and cytogenetic damage. The studies have linked the gene deletion of GSTM1 to susceptibility to various cancers, including lung, bladder, Head, Neck, Colon and basal cell carcinoma. Variation in metabolism of carcinogens could increase or decrease exposure of cells to carcinogens. Ethnic variation in cancer incidence and mortality may be due in part because of differences in the distribution of polymorphisms, as well as differences in environmental and dietary exposures.

2019 ◽  
Vol 2 (2) ◽  
pp. 1-21 ◽  
Author(s):  
Elina Mitra ◽  
Bharati Bhattacharjee ◽  
Palash Kumar Pal ◽  
Arnab Kumar Ghosh ◽  
Sanatan Mishra ◽  
...  

Cadmium (Cd) is a notorious environmental pollutant known for its wide range of toxicities to organisms. Thus, the present study is designed to examine whether melatonin, a potent antioxidant, protects against Cd-induced oxidative damage in the heart, liver and kidney of rats. Cd treatment at a dose of 0.44 mg/kg for 15 days caused severe damage in all these organs. These included significantly increased activities of SGPT, SGOT, lactate dehydrogenase- 1 and 5 and ALP and levels of total lactate, creatinine, lipid peroxidation, protein carbonyl content and reduced glutathione while the activities of superoxide dismutases, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase along with mitochondrial pyruvate dehydrogenase, isocitrate dehydrogenase, α-keto glutarate dehydrogenase, succinate dehydrogenase, NADH-cytochrome-c-oxidoreductase and cytochrome-c-oxidase were significantly reduced by Cd. However, if melatonin was given orally 30 min before Cd injection, all these alterations induced by Cd were significantly preserved by melatonin. Histological observations also demonstrated that Cd exposure caused cellular lesions, promoting necrotic or apoptotic changes. Notably, all these changes were significantly protected by melatonin. The results suggest that melatonin is a beneficial molecule to ameliorate Cd-induced oxidative damage in the heart, liver and kidney tissues of rats with its powerful antioxidant capacity, heavy metal chelating activity and competition of binding sites with Cd to the GSH and catalase.


Arthroplasty ◽  
2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Toni Wendler ◽  
Torsten Prietzel ◽  
Robert Möbius ◽  
Jean-Pierre Fischer ◽  
Andreas Roth ◽  
...  

Abstract Background All current total hip arthroplasty (THA) systems are modular in design. Only during the operation femoral head and stem get connected by a Morse taper junction. The junction is realized by hammer blows from the surgeon. Decisive for the junction strength is the maximum force acting once in the direction of the neck axis, which is mainly influenced by the applied impulse and surrounding soft tissues. This leads to large differences in assembly forces between the surgeries. This study aimed to quantify the assembly forces of different surgeons under influence of surrounding soft tissue. Methods First, a measuring system, consisting of a prosthesis and a hammer, was developed. Both components are equipped with a piezoelectric force sensor. Initially, in situ experiments on human cadavers were carried out using this system in order to determine the actual assembly forces and to characterize the influence of human soft tissues. Afterwards, an in vitro model in the form of an artificial femur (Sawbones Europe AB, Malmo, Sweden) with implanted measuring stem embedded in gelatine was developed. The gelatine mixture was chosen in such a way that assembly forces applied to the model corresponded to those in situ. A study involving 31 surgeons was carried out on the aforementioned in vitro model, in which the assembly forces were determined. Results A model was developed, with the influence of human soft tissues being taken into account. The assembly forces measured on the in vitro model were, on average, 2037.2 N ± 724.9 N, ranging from 822.5 N to 3835.2 N. The comparison among the surgeons showed no significant differences in sex (P = 0.09), work experience (P = 0.71) and number of THAs performed per year (P = 0.69). Conclusions All measured assembly forces were below 4 kN, which is recommended in the literature. This could lead to increased corrosion following fretting in the head-neck interface. In addition, there was a very wide range of assembly forces among the surgeons, although other influencing factors such as different implant sizes or materials were not taken into account. To ensure optimal assembly force, the impaction should be standardized, e.g., by using an appropriate surgical instrument.


2021 ◽  
Vol 22 (5) ◽  
pp. 2754
Author(s):  
Naila Qayyum ◽  
Muhammad Haseeb ◽  
Moon Suk Kim ◽  
Sangdun Choi

Thioredoxin-interacting protein (TXNIP), widely known as thioredoxin-binding protein 2 (TBP2), is a major binding mediator in the thioredoxin (TXN) antioxidant system, which involves a reduction-oxidation (redox) signaling complex and is pivotal for the pathophysiology of some diseases. TXNIP increases reactive oxygen species production and oxidative stress and thereby contributes to apoptosis. Recent studies indicate an evolving role of TXNIP in the pathogenesis of complex diseases such as metabolic disorders, neurological disorders, and inflammatory illnesses. In addition, TXNIP has gained significant attention due to its wide range of functions in energy metabolism, insulin sensitivity, improved insulin secretion, and also in the regulation of glucose and tumor suppressor activities in various cancers. This review aims to highlight the roles of TXNIP in the field of diabetology, neurodegenerative diseases, and inflammation. TXNIP is found to be a promising novel therapeutic target in the current review, not only in the aforementioned diseases but also in prolonged microvascular and macrovascular diseases. Therefore, TXNIP inhibitors hold promise for preventing the growing incidence of complications in relevant diseases.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nermin S. Ahmed ◽  
Marek Samec ◽  
Alena Liskova ◽  
Peter Kubatka ◽  
Luciano Saso

AbstractTamoxifen is the gold standard drug for the treatment of breast cancer in pre and post-menopausal women. Its journey from a failing contraceptive to a blockbuster is an example of pharmaceutical innovation challenges. Tamoxifen has a wide range of pharmacological activities; a drug that was initially thought to work via a simple Estrogen receptor (ER) mechanism was proven to mediate its activity through several non-ER mechanisms. Here in we review the previous literature describing ER and non-ER targets of tamoxifen, we highlighted the overlooked connection between tamoxifen, tamoxifen apoptotic effects and oxidative stress.


Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 114
Author(s):  
Pahriya Ashrap ◽  
Deborah J. Watkins ◽  
Ginger L. Milne ◽  
Kelly K. Ferguson ◽  
Rita Loch-Caruso ◽  
...  

Metal exposure has been associated with a wide range of adverse birth outcomes and oxidative stress is a leading hypothesis of the mechanism of action of metal toxicity. We assessed the relationship between maternal exposure to essential and non-essential metals and metalloids in pregnancy and oxidative stress markers, and sought to identify windows of vulnerability and effect modification by fetal sex. In our analysis of 215 women from the PROTECT birth cohort study, we measured 14 essential and non-essential metals in urine samples at three time points during pregnancy. The oxidative stress marker 8-iso-prostaglandin F2α (8-iso-PGF2α) and its metabolite 2,3-dinor-5,6-dihydro-15-15-F2t-IsoP, as well as prostaglandin F2α (PGF2α), were also measured in the same urine samples. Using linear mixed models, we examined the main effects of metals on markers of oxidative stress as well as the visit-specific and fetal sex-specific effects. After adjustment for covariates, we found that a few urinary metal concentrations, most notably cesium (Cs) and copper (Cu), were associated with higher 8-iso-PGF2α with effect estimates ranging from 7.3 to 14.9% for each interquartile range, increase in the metal concentration. The effect estimates were generally in the same direction at the three visits and a few were significant only among women carrying a male fetus. Our data show that higher urinary metal concentrations were associated with elevated biomarkers of oxidative stress. Our results also indicate a potential vulnerability of women carrying a male fetus.


2018 ◽  
Vol 314 (4) ◽  
pp. L642-L653 ◽  
Author(s):  
Louise Hecker

The rapid expansion of the elderly population has led to the recent epidemic of age-related diseases, including increased incidence and mortality of chronic and acute lung diseases. Numerous studies have implicated aging and oxidative stress in the pathogenesis of various pulmonary diseases; however, despite recent advances in these fields, the specific contributions of aging and oxidative stress remain elusive. This review will discuss the consequences of aging on lung morphology and physiology, and how redox imbalance with aging contributes to lung disease susceptibility. Here, we focus on three lung diseases for which aging is a significant risk factor: acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). Preclinical and clinical development for redox- and senescence-altering therapeutic strategies are discussed, as well as scientific advancements that may direct current and future therapeutic development. A deeper understanding of how aging impacts normal lung function, redox balance, and injury-repair processes will inspire the development of new therapies to prevent and/or reverse age-associated pulmonary diseases, and ultimately increase health span and longevity. This review is intended to encourage basic, clinical, and translational research that will bridge knowledge gaps at the intersection of aging, oxidative stress, and lung disease to fuel the development of more effective therapeutic strategies for lung diseases that disproportionately afflict the elderly.


Cosmetics ◽  
2021 ◽  
Vol 8 (4) ◽  
pp. 111
Author(s):  
Punniamoorthy Thiviya ◽  
Ashoka Gamage ◽  
Dinushika Piumali ◽  
Othmane Merah ◽  
Terrence Madhujith

The excess level of reactive oxygen species (ROS) disturbs the oxidative balance leading to oxidative stress, which, in turn, causes diabetes mellites, cancer, and cardiovascular diseases. These effects of ROS and oxidative stress can be balanced by dietary antioxidants. In recent years, there has been an increasing trend in the use of herbal products for personal and beauty care. The Apiaceae (previously Umbelliferae) family is a good source of antioxidants, predominantly phenolic compounds, therefore, widely used in the pharmaceutical, cosmetic, cosmeceutical, flavor, and perfumery industries. These natural antioxidants include polyphenolic acids, flavonoids, carotenoids, tocopherols, and ascorbic acids, and exhibit a wide range of biological effects, including anti-inflammatory, anti-aging, anti-atherosclerosis, and anticancer. This review discusses the Apiaceae family plants as an important source of antioxidants their therapeutic value and the use in cosmetics.


2010 ◽  
Vol 43 (13-14) ◽  
pp. 1124-1128 ◽  
Author(s):  
M.D. Mustafa ◽  
Rahul Pathak ◽  
Tanzeel Ahmed ◽  
Rafat S. Ahmed ◽  
A.K. Tripathi ◽  
...  

1994 ◽  
Vol 1 (3) ◽  
pp. 169-175 ◽  
Author(s):  
J Chamberlain

Screening infants for the early detection of neuroblastoma is advocated by many paediatric oncologists and is practised in a limited number of places in the developed world, most notably in Japan where a national screening programme has been in operation since 1985. The screening test consists of measurements of the levels of vanillylmandelic acid and homovanillic acid in the urine; these metabolites of catecholamine are excreted in the urine of 92% of patients with clinically presenting neuroblastoma. The prognosis for children with symptomatic neuroblastoma is dependent both on age and stage, with children aged under 1 year and those with tumours of stages I, II, and IVS having a much better prognosis. Screening aims at detecting and treating during the first year those neuroblastomas which would otherwise present at an advanced stage in older children. Evidence from Japan shows that screening achieves the interim outcomes of a shift in the age distribution and stage distribution of neuroblastomas in populations for whom screening has been provided, and that survival of subjects detected by screening is over 90%, compared with around 50% for symptomatic subjects. However, there is not yet any clear evidence that screening results in a reduction in the incidence of advanced neuroblastoma in children over the age of 1, nor a reduction in mortality. Recent cross sectional analyses of age specific incidence and mortality suggest that screening may be having a limited effect, but as yet no analysis of these outcomes in cohorts for whom screening has been provided has been published. Other factors, such as improved chemotherapy, may also be contributing to lower mortality. A number of missed (interval) cancers have been diagnosed in children who screened negative both in the Japanese programme and in Canadian and English studies, indicating that there is a problem with the sensitivity of screening. But the screening test is highly specific with less than 0.1% of infants having false positive results requiring investigation. The natural history of neuroblastoma ranges from highly malignant tumours to biologically benign variants that regress without active treatment, the prevalence of the latter being inversely related to age. Serial measurements of biological markers, including ploidy, chromosome 1p deletion, and N-mycamplification, performed within the same patient at different times indicate that malignant potential does not progress over time. The distribution of these markers in cases detected by screening shows that they are inherently tumours with a good prognosis, whereas the reverse is true of interval cases. Thus screening is differentially picking up the tumours that are least likely to progress and failing to detect at least some tumours of those destined to die from the disease. Comparison of the yield of cancers detected by screening and the expected cumulative incidence of neuroblastoma throughout childhood suggest that screening “overdiagnoses” many nonprogressive cases, with consequent physical and psychological morbidity. On balance present evidence suggests that the number of deaths that could be prevented by screening is small and the potential for overdiagnosis is great. Unless further evidence from Japan or the results of a current North American trial conclude otherwise, screening cannot be recommended.


1996 ◽  
Vol 16 (10) ◽  
pp. 5264-5275 ◽  
Author(s):  
E Bi ◽  
J R Pringle

A genetic screen for GTPase-activating proteins (GAPs) or other negative regulators of the Rac/Rho family GTPase Cdc42p in Saccharomyces cerevisiae identified ZDS1, a gene encoding a protein of 915 amino acids. Sequence from the yeast genome project identified a homolog, ZDS2, whose predicted product of 942 amino acids is 38% identical in sequence to Zds1p. Zds1p and Zds2p have no detectable homology to known Rho-GAPs or to other known proteins. However, by several assays, it appears that overexpression of either Zds1p or Zds2p decreases the level of Cdc42p activity. Deletion analysis also suggests that Zds1p and Zds2p are at least partially overlapping in function. Deletion of ZDS2 produced no obvious phenotype, and deletion of ZDS1 produced no obvious phenotype other than a mild effect on cell shape. However, the zds1 zds2 double mutant grew slowly with an apparent mitotic delay and produced elongated cells and buds with other evidence of abnormal morphogenesis. A glutathione S-transferase-Zds1p fusion protein that fully complemented the double mutant localized to presumptive bud sites and the tips of small buds. The similarity of this localization to that of Cdc42p suggests that Zds1p may interact directly with Cdc42p. As ZDS1 and ZDS2 have recently been identified also by numerous other groups studying a wide range of biological phenomena, the roles of Cdc42p in intracellular signaling may be more diverse than has previously been appreciated.


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