The Human Genome

2015 ◽  
Vol 27 (1) ◽  
pp. 25-44
Author(s):  
Gerald Bergman ◽  
Keyword(s):  
Genetic Variation ◽  
Adverse Effects ◽  
Beneficial Effect ◽  
Human Genome ◽  
Scientific Literature ◽  
Genetic Change ◽  
Medical Community ◽  
Deleterious Mutations ◽  
Beneficial Effects ◽  
Gene Damage

This essay explores the influence of randomness in genetic change based on findings in the scientific literature. In many cases, random mutations are not the source of genetic variation that allows adaptation to an environmental change. Rather, innate mechanisms are the cause. Typical examples are used to illustrate how these systems work, and the evidence for them. Randomness appears to have less effect in causing micro-evolution then once assumed. But it has a significant influence in causing near neutral and deleterious mutations, resulting in genetic entropy. Some random mutations have a beneficial effect. However, all are due to gene damage that in some situations have limited beneficial effects. This suggests that major steps should be taken by the medical community to help ameliorate the adverse effects of random mutations on the human genome.

Helenalin: An Anti-Inflammatory and Anti-Neoplastic Agent: A Review

2020 ◽  
Vol 16 (8) ◽  
pp. 1134-1146
Author(s):  
Priyanka Kriplani ◽  
Kumar Guarve ◽  
Uttam S. Baghel
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Effects ◽  
Chronic Conditions ◽  
Review Article ◽  
Google Scholar ◽  
Medical Community ◽  
Inflammatory Agent ◽  
Skin Cancers ◽  
Medicinal Properties ◽  
Anti Inflammatory

Objective: Helenalin is a natural anti-inflammatory agent that is proving its efficacy to treat various medical conditions. Though many plants are proving their effectiveness but their mechanisms are still not well understood. The objective of the review is to summarize various mechanisms of helenalin to treat inflammatory disorders and cancers, adverse effects, and avenues of further research. Methods: Structured research was carried out including Pub med, Science direct Medline, Research Gate and Google Scholar to find all articles published on helenalin. Various keywords used were “helenalin”, “Arnica”, “cancer”, “anti-inflammatory”, “cardiovascular”, “IBD”, “pharmacokinetics” etc. The aim of the review was to find out the problem prevailing in the data published to date which will help the researchers to investigate the molecule clinically. Results: Seventy articles are included in the review. Helenalin is found to cure chronic conditions like rheumatoid arthritis, ulcers and malignancies like stomach, colon, breast, larynx, lung and skin cancers via multiple mechanisms. These diseases do not proceed via a unilateral pathway. So, it can be a useful molecule to treat numerous diseases. Conclusion: This review article will help us to systemically analyze the wealth of information concerning the medicinal properties of helenalin and to recognize the gaps which have vetoed its pervasive application in the medical community.

scholarly journals Characterization of Deleterious Mutations in Outcrossing Populations

Genetics ◽  
1998 ◽  
Vol 150 (2) ◽  
pp. 945-956 ◽  
Author(s):  
Hong-Wen Deng
Keyword(s):  
Genetic Variation ◽  
Genetic Variance ◽  
Estimation Bias ◽  
Deleterious Mutations ◽  
Environmental Variance ◽  
Higher Power ◽  
Sib Mating ◽  
The Mean ◽  
Simulation Results

Abstract Deng and Lynch recently proposed estimating the rate and effects of deleterious genomic mutations from changes in the mean and genetic variance of fitness upon selfing/outcrossing in outcrossing/highly selfing populations. The utility of our original estimation approach is limited in outcrossing populations, since selfing may not always be feasible. Here we extend the approach to any form of inbreeding in outcrossing populations. By simulations, the statistical properties of the estimation under a common form of inbreeding (sib mating) are investigated under a range of biologically plausible situations. The efficiencies of different degrees of inbreeding and two different experimental designs of estimation are also investigated. We found that estimation using the total genetic variation in the inbred generation is generally more efficient than employing the genetic variation among the mean of inbred families, and that higher degree of inbreeding employed in experiments yields higher power for estimation. The simulation results of the magnitude and direction of estimation bias under variable or epistatic mutation effects may provide a basis for accurate inferences of deleterious mutations. Simulations accounting for environmental variance of fitness suggest that, under full-sib mating, our extension can achieve reasonably well an estimation with sample sizes of only ∼2000-3000.

scholarly journals Removal of sacral neuromodulation quadripolar tined-lead using a straight stylet: description of a surgical technique

2021 ◽  
Author(s):  
M. Agnello ◽  
M. Vottero ◽  
P. Bertapelle
Keyword(s):  
Adverse Effects ◽  
Sacral Neuromodulation ◽  
Pulse Generator ◽  
Lead Removal ◽  
Open Technique ◽  
Implantable Pulse Generator ◽  
Beneficial Effects ◽  
Tined Lead ◽  
Removal Technique ◽  
Sacral Bone

Abstract Background Up to 7.5% of tined-lead removals in patients having sacral neuromodulation (SNM) therapy are associated with a lead breakage. It is still unclear what adverse effects can be caused by unretrieved fragments. The aim of our study was to describe the lead removal technique we have been using for the last 2 years in our centre. Methods We retrospectively enrolled patients who had lead removal between January 2018 and January 2020 using our standardized technique. The novelty of the technique is in the use of the straight stylet, which is available in the quadripolar tined-lead kit. The stylet gives the electrode greater stiffness, reducing interactions with surrounding tissues and probability of damage or breakage during removal. Results In 59 patients (42 women, mean age 57.2 years [range 40–79 years]) the lead was removed using our standardized technique. In 44 of 59 patients, the tined-lead was removed within 2 months from the SNM-test, due to lack of beneficial effects. In 15 patients the electrode was removed because of failure of definitive implantation. Meantime from definitive implantable pulse generator (IPG) implantation to lead removal was 67.9 months. We recorded only 1 case of lead-breakage during removal: a female patient with a non-tined lead fixed on sacral bone, placed 18 years previously using an open technique. Conclusions Lead breakage during removal is not uncommon and adverse effects of retained fragments may occur. Our technique has been safely used for the last 2 years in our centre, with no episodes of lead breakage or retained fragments, except for one non-tined electrode.

Revitalizing Difference in the HapMap: Race and Contemporary Human Genetic Variation Research

2008 ◽  
Vol 36 (3) ◽  
pp. 471-477 ◽  
Author(s):  
Jennifer A. Hamilton
Keyword(s):  
Genetic Variation ◽  
Human Genome ◽  
Genetic Research ◽  
The United States ◽  
Genome Project ◽  
Human Genetic Variation ◽  
Early 21St Century ◽  
The Social ◽  
English Speaking ◽  
The Human Genome Project

In 2000, researchers from the Human Genome Project (HGP) proclaimed that the initial sequencing of the human genome definitively proved, among other things, that there was no genetic basis for race. The genetic fact that most humans were 99.9% the same at the level of their DNA was widely heralded and circulated in the English-speaking press, especially in the United States. This pronouncement seemed proof that long-term antiracist efforts to de-biologize race were legitimized by scientific findings. Yet, despite the seemingly widespread acceptance of the social construction of race, post-HGP genetic science has seen a substantial shift toward the use of race variables in genetic research and, according to a number of prominent scholars, is re-invoking the specter of earlier forms of racial science in some rather discomfiting ways. During the past seven years, the main thrust of human genetic research, especially in the realm of biomedicine, has shifted from a concern with the 99.9% of the shared genome — what is thought to make humans alike — towards an explicit focus on the 0.1% that constitutes human genetic variation. Here I briefly explore some of the potential implications of the conceptualization and practice of early 21st century genetic variation research, especially as it relates to questions of race.

scholarly journals Systematic Review of Adverse Effects: A Further Step towards Modernization of Acupuncture in China

2015 ◽  
Vol 2015 ◽  
pp. 1-19 ◽  
Author(s):  
Junyi Wu ◽  
Yanmei Hu ◽  
Yin Zhu ◽  
Ping Yin ◽  
Gerhard Litscher ◽  
...  
Keyword(s):  
Patient Outcome ◽  
Systematic Review ◽  
Central Nervous System ◽  
Adverse Effects ◽  
Scientific Literature ◽  
Acupuncture Treatment ◽  
Case Reports ◽  
The World ◽  
Organ Tissue

As a further step towards the modernization of acupuncture, the objective of this review was to figure out the frequency and severity of adverse complications and events in acupuncture treatment reported from 1980 to 2013 in China. All first-hand case reports of acupuncture-related complications and adverse events that could be identified in the scientific literature were reviewed and classified according to the type of complication and adverse event, circumstance of the event, and long-term patient outcome. The selected case reports were published between 1980 and 2013 in 3 databases. Relevant papers were collected and analyzed by 2 reviewers. Over the 33 years, 182 incidents were identified in 133 relevant papers. Internal organ, tissue, or nerve injury is the main complications of acupuncture especially for pneumothorax and central nervous system injury. Adverse effects also included syncope, infections, hemorrhage, allergy, burn, aphonia, hysteria, cough, thirst, fever, somnolence, and broken needles. Qualifying training of acupuncturists should be systemized and the clinical acupuncture operations should be standardized in order to effectively prevent the occurrence of acupuncture accidents, enhance the influence of acupuncture, and further popularize acupuncture to the rest of the world.

scholarly journals Genetic variations in the drug metabolizing enzyme, CYP2E1, among various ethnic populations of Pakistan

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9721
Author(s):  
Sagheer Ahmed ◽  
Nadeem Altaf ◽  
Mahnoor Ejaz ◽  
Zaira Zulfiqar ◽  
Kholood Janjua ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Adverse Effects ◽  
Drug Response ◽  
Variable Response ◽  
Healthy Human ◽  
Pakistani Population ◽  
Drug Metabolizing Enzyme ◽  
Different Populations ◽  
Metabolizing Enzyme ◽  
Low Activity

Genetic polymorphism in cytochrome P450 (CYP) monooxygenase genes is an important source of interindividual variability of drug response. CYP enzyme activities may change as a result of such polymorphisms which then, may affect drug metabolism. This would result in a change in the severity and frequency of adverse effects in addition to the non-responder phenomenon. CYP2E1, a member of CYP superfamily, affects the metabolism of several clinically important drugs such as halothane, paracetamol, etc. Genetic variation in CYP2E1 is known to cause significant inter-individual differences in drug response and adverse effects. The degree of genetic variation is found to be different in different populations around the world. The frequencies of two important polymorphisms in the CYP2E1*7C, NC_000010.10:g.135340548A>G (rs2070672) and CYP2E1, NC_000010.10:g.135339244G>C (rs3813865), are not known in the Pakistani population. In the present investigation, 636 healthy human volunteers were screened for these two single nucleotide polymorphism. Our results indicate that about 18% (rs2070672) and 28% (rs3813865) of the Pakistani population has a genotype containing at least one low activity allele. A significant interethnic variation in the frequencies of both the polymorphisms was observed. These results suggest that pharmacogenetics screening for low activity genotypes would be a helpful tool for clinicians when they prescribe medications metabolized by CYP2E1, as a significant fraction of the Pakistani population is expected to have a variable response to these drugs.

scholarly journals Effectiveness of aronia berries for reduction of mild fibrosis and gene expression analysis in livers from mice fed a high-fat diet with aronia berries

2016 ◽  
Vol 6 (3) ◽  
pp. 144 ◽  
Author(s):  
Takuya Yamane ◽  
Miyuki Kozuka ◽  
Yoshio Yamamoto ◽  
Yoshihisa Nakano ◽  
Takenori Nakagaki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Liver Fibrosis ◽  
Beneficial Effect ◽  
Rna Sequencing ◽  
Expression Analysis ◽  
High Fat Diet ◽  
Gene Expression Analysis ◽  
High Fat ◽  
Expression Levels ◽  
Beneficial Effects

Background: Aronia berries have many potential effects on health, including an antioxidant effect, effect for antimutagenesis, hepatoprotection and cardioprotection, an antidiabetic effect and inhibition of cancer cell proliferation. Previous human studies have shown that aronia juice may be useful for treatment of obesity disorders.Objective: To reveal relationship between beneficial effect and the gene expression change by aronia berries, we analyzed mice livers using RNA sequencing and RT-qPCR.Method: At 28 days after starting a normal diet, a high fat diet and a high-fat diet containing 10% freeze-dried aronia berries, serum was obtained from veins of mice after isoflurane anesthesia, and liver tissues were isolated and weighed. Triglyceride, total cholesterol and LDL cholesterol levels were measured and total RNAs were extracted. cDNA libraries were prepared according to Illumina protocols and sequenced using an Illumina HiSeq2500 to perform 100 paired-end sequencing. RNA-sequence reads mapping was performed using a DNA nexus. Gene expression analysis was performed. The liver tissue specimens were fixed and embedded in paraffin. After 5-mm-thick paraffin sections had been cut, they were stained with hematoxylin-eosin using the standard procedure and also with Sirius Red.Results: In this study, we found that mild fibrosis induced by a high-fat diet was reduced in livers of mice fed a high-fat diet containing aronia berries. RNA sequencing and RT-qPCR analyses revealed that gene expression levels of Igfbp1 and Gadd45g were increased in livers from mice fed a high-fat diet containing aronia berries. Furthermore, results of an enzyme-linked immunoassay showed that a secreted protein levels of FABP1 and FABP4 were reduced in serum from mice fed a high-fat diet containing aronia berries. The results suggest that aronia berries have beneficial effects on mild fibrosis in liver.Conclusion: Aronia berries have a beneficial effect on liver fibrosis. The recovery from liver fibrosis is associated with expression levels of Gadd45g and Igfbp1 in the liver. The beneficial effects of aronia berries on liver fibrosis reduce the risk of liver cancer diseases and insulin resistance, resulting in reduction of serum FABP1 and FABP4 levels.Keywords: aronia; fibrosis; liver; Igfbp1; Gadd45g

Beneficial effects of alternative lighting schedules on the incidence of ascites and on metabolic parameters of broiler chickens

2003 ◽  
Vol 51 (4) ◽  
pp. 513-520 ◽  
Author(s):  
M. Hassanzadeh ◽  
M. H. Bozorgmehri Fard ◽  
J. Buyse ◽  
E. Decuypere
Keyword(s):  
Beneficial Effect ◽  
Sea Level ◽  
Minimum Temperature ◽  
Broiler Chickens ◽  
Right Ventricular Failure ◽  
Ventricular Failure ◽  
Temporary Reduction ◽  
Relative Growth ◽  
Beneficial Effects ◽  
The Third

The beneficial effects of different lighting programmes on the incidence of ascites was investigated in an experiment with 360 three-day-old male broiler chickens. At 3 days of age, chicks were randomly divided over three rooms in a high-altitude farm, 2000 m above sea level. During days 14 to 28 ambient temperature decreased during the night but the minimum temperature did not descend below 15°C. In the first room the continuous lighting schedule (CL, 23L:1D) was maintained and in the second room an intermittent lighting schedule (IL, 1L:3D), repeated six times daily, was imposed from 3 days of age. In the third room, an increasing photoperiod schedule (IP, 4 to 14 days, 6L:18D; 15 to 21 days, 10L:14D; 22 to 28 days, 14L:10D; 29 to 35 days, 18L:6D; 36 to 42 days, 23L:1D) was provided. Mortality associated with right ventricular failure and ascites was numerically lower in birds reared under the IL and IP schedules compared to birds reared under the CL schedule, which can be attributed to the temporary reduction in relative growth and feed intake in IL and IP birds. It was concluded that the beneficial effect of lighting schedules could be due to a reduced metabolic rate as a consequence of the altered growth trajectory, as also reflected in the lower haematocrit and plasma T3 levels of IL and IP birds compared to CL birds.

Abstract 69: Anacetrapib Dose-dependently Decreases Atherosclerosis Development and Adds to the Beneficial Effects of Atorvastatin in APOE*3Leiden.CETP Mice

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Susan Kühnast ◽  
Sam J van der Tuin ◽  
Louis M Havekes ◽  
Ko Willems van Dijk ◽  
Patrick C Rensen ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Plasma Lipids ◽  
Atherosclerotic Lesion ◽  
Hdl Cholesterol ◽  
Statin Treatment ◽  
Epidemiological Studies ◽  
Lesion Size ◽  
Beneficial Effects ◽  
Atherosclerosis Development ◽  
C 32

Introduction The residual risk of cardiovascular disease that remains after statin treatment has triggered the search for a secondary treatment target. Epidemiological studies propose HDL-cholesterol (HDL-C) as a possible candidate. Cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from atheroprotective HDL to atherogenic (V)LDL. In human intervention trials, the CETP inhibitor anacetrapib decreases (V)LDL-C by 30-40% and increases HDL-C by 40-140%. Hypothesis Complete inhibition of CETP activity may result in adverse effects as compared to partial inhibition due to the appearance of a dysfunctional HDL. We, therefore, evaluated the effect of a broad treatment window of anacetrapib-induced CETP inhibition with partial to full inhibition, as well as the combination of atorvastatin and anacetrapib on atherosclerosis development in APOE*3Leiden.CETP mice. Methods Female mice were fed a Western-type diet containing 0.1% cholesterol without or with incremental dosages of anacetrapib (0.03; 0.3; 3; 30 mg/kg/d), atorvastatin (2.4 mg/kg/d) or a combination of anacetrapib (0.3 mg/kg/d) and atorvastatin (2.4 mg/kg/d) for 20 weeks. Effects on plasma lipids, CETP activity and levels, as well as atherosclerotic lesion size and severity were assessed. Results Anacetrapib dose-dependently reduced CETP activity (-60% to -100%, P<0.001) and increased CETP levels (+13% to +31%, P<0.05), thereby decreasing nonHDL-C (-23% to -44%, P<0.001) and increasing HDL-C (+32% to +88%, P<0.001). Atorvastatin decreased CETP activity (-29%, P<0.001) and nonHDL-C (-36%, P<0.001). Anacetrapib dose-dependently decreased atherosclerotic lesion size (-36%, P<0.05 to -92%, P<0.001) and the percentage severe lesions. Anacetrapib added to the effects of atorvastatin by further reducing nonHDL-C (-36%, P<0.001), increasing HDL-C (+72%, P<0.001) and decreasing lesion size (-86%, P<0.001) and severity. Results on lesion composition are pending. Conclusions Anacetrapib dose-dependently decreases atherosclerosis development and adds to the beneficial effects of atorvastatin in APOE*3Leiden.CETP mice. Total blockage of CETP activity does not reveal adverse effects as compared to partial blockage.

Mineralocorticoid receptor antagonists

ESC CardioMed ◽  
2018 ◽  
pp. 167-173
Author(s):  
Faiez Zannad ◽  
João Pedro Ferreira
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Adverse Effects ◽  
Beneficial Effect ◽  
Mechanism Of Action ◽  
Mineralocorticoid Receptor ◽  
Post Myocardial Infarction ◽  
Mineralocorticoid Receptor Antagonists ◽  
Receptor Antagonists ◽  
Clinical Syndromes

Hypertension, post-myocardial infarction, and heart failure are the cardiovascular clinical syndromes where mineralocorticoid receptor antagonists (MRAs) have shown a beneficial effect. Most guidelines while recommending a MRA do not make a clear recommendation as to which MRA should be used, how doses should be titrated, or which monitorization is indicated. This chapter provides an appraisal of the different types of MRA drugs and their pharmacological differences with respect to mechanism of action, pharmacokinetics, monitoring, adverse effects, and drug interactions.

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