Therapeutic Synthesis

A twenty-five-year old Caucasian female presented to the office with burning with urination. External inspection of the patient’s labia majora revealed genital herpes. Herpes simplex virus infections associated with the genitals are usually deemed type two (Uphold & Graham, 2013). The patient was placed on acyclovir for her outbreak. The current dosage that she is being placed on is 400 mg orally every eight hours for ten days (Medscape, n.d.). There are no medication contraindications for this drug; however, one should not use neomycin orally due to an increase in nephrotoxicity and or otoxicity if the two are taken together (Medscape, n.d.). Other medications such as bacitracin and cidofovir should also not be used with acyclovir due to an increase in nephrotoxicity and or otoxicity if these are

In this lab, we used two different strains of Saccharomyces cerevisiae (yeast) cells. One of them was, Saccharomyces cerevisiae, UV-Sensitive Strain, G948-1C/U, alpha, rad1 rad18 phr1 ura3 mutant in excision repair (Haploid), while the other was a wild type strain of this yeast. We chose to do this, because it is important to compare UV sensitive yeast cells, which have a mutation that yields them unable to repair themselves, to a wild type that is able to repair itself after UV radiation exposure. According to Conconi, “monitoring the formation of formazan in non-dividing yeast cells that are partially (rad7Δ) or totally (wt) proficient at DNA repair is a more accurate measure of cell survival after

On December 10, 2015, three profound individuals received the Nobel Prize in chemistry for their work on DNA repair systems. Paul Modrich, Thomas Lindahl, and Aziz Sancar studied how the cell repairs and protects the information held in its DNA; specifically, Paul Modrich focused on DNA mismatch repair. Since DNA constantly replicates, damage and incorrect pairings are expected, but enzymes watch over DNA as it replicates and repair any errors that occur. In the mismatch repair system, enzymes find the mismatch in the copy of DNA, cut the incorrect section out, and replace it with the correct sequence. Paul Modrich’s study of the mismatch repair system has provided the medical field with important information regarding cancer growth and the possibility of a cure.

The patient is an eight-year old girl who is taking hydrocortisone, neomycin, and polymyxin eardrops for the diagnosis of a bacterial ear infection. The dose is 10mg (1%)/3.5mg (0.35%)/10000 units/10ml and was instructed to take this medication every six to eight hours with three drops in the affected ear. The medication has multiple classes since this medication contains multiple drugs. Hydrocortisone is a corticosteroid medication that works to decrease inflammation within the ear. Neomycin and polymyxin are within the antibacterial class and work to combat infection. The combination of the drug helps to eliminate the bacteria within the ear; decrease pain, redness, and itching that were accompanying her bacterial

The organ is a beautifully complex instrument. In the performance by Dr. Stephen Self, the vast ability of both the instrument and the organist were exhibited. Before a note was played, the splendor of the instrument could be observed with the beauty and multitude of the pipes visible in the facade. The majesty of the event continued with the confidence and calmness with which Dr. Self approached the organ console. With the first note, the resonance of the organ was communicated. From a memorable piece to a technical performance, a relaxing melody to a powerful piece, this performance displayed the versatility of the organ and the organist alike.

We further wanted to determine the level of DNA damage in ATII cells isolated from emphysema patients compared to control non-smokers or smokers. We analyzed phosphorylation of H2AX (γH2AX), which is a sensitive indicator of DSBs (REF), by Western blotting and immunohistofluorescence. We found significantly higher γH2AX phosphorylation in ATII cells obtained from smokers in comparison with non-smokers (p<0.05; Figs. 2a, b). Interestingly, ATII cells isolated from emphysema patients have lower expression of γH2AX phosphorylation in comparison with smokers. We also determined γH2AX phosphorylation in lung tissue sections by immunohistofluorescence using SP-A as a marker of ATII cells. We obtained similar results showing higher γH2AX florescence intensity in ATII cells obtained from smokers in comparison with control non-smokers and emphysema (p< 0.05; Figs. 2c, d). Although, ATII cells isolated from emphysema patients have higher ROS levels (Figs. 1a, b), they don’t show a significant increase in γH2AX phosphorylation. This may suggest the impairment of DSBs repair signaling leading to lack of the DNA damage repair in these cells.

Saccharomyces cerevisiae was tested for the effects of ultraviolet (UV) irradiation in the presence of caffeine to observe whether the drug would enhance or inhibit the DNA’s recombinational repair process after the yeast has experienced UV damage. We hypothesized that caffeine would obstruct the yeast’s DNA repair process by interrupting its recombinational process post UV-irradiation, and we predicted that increasing caffeine levels would decrease percent survival. By exposing the yeast to three different caffeine concentrations (0, 5, and 10 mM) at 1x104 microjoules/cm2 of UV irradiation, we measured the effects of caffeine dosage on DNA repair. We reported that an increase in the caffeine concentration level causes a decrease in the percent survival, supporting our hypothesis. Caffeine, therefore, can be perceived as a model compound in the nullification of DNA-damage checkpoints. Moreover, the inhibition of the recombinational repair process provides a molecular explanation for the reduction of DNA-damage checkpoint responses and for the increased UV-sensitivity of caffeine-treated yeast cells.

The most reasonable inference from the observation that defects in DNA repair enzymes contribute to some cancers is that:

Cancer cells are able to accumulate mutations, which make them have a more aggressive phenotype, because they express defects in DNA repair pathways. Because PARP-1 participates in the repair of DNA, it has become a target for the development of new drugs that would make the DNA repair pathways in which PARP-1 participates nonfunctional. This would allow the cancerous cells to accumulate many more

DNA Double Strand Breaks (DSBs) are valuable when controlled, but potentially fatal when not – the programmed DSB is an essential part of particular cellular processes (e.g. VDJ switch recombination during immune system development and during homologous recombination in meiosis and mitosis), but an unprogrammed DSB is also considered the most lethal type of lesion for a cell (Sedelnikova et al., 2003). Cells are confronted with DNA damage due to a variety of stimuli under normal physiological conditions and at each instance the cell must make a decision concerning the ratio of DNA repair and apoptotic response (Cook et al., 2009). This response entails firstly the detection of DNA damage among the undamaged DNA, and secondly a signal amplification

The exposure of skin to ultraviolet B (UVB) radiation has a destructive effect on keratinocytes by causing DNA damage that can subsequently lead to malignant transformation. Cellular defense mechanisms against this injury begin with the immediate UVB induced death of damaged cells. In less severely affected cells, cellcycle progression can be blocked and DNA damage can be repaired through nucleotideexcision repair (NER). If repair is successful and cells have not suffered irreversible damage, they will survive.

Combination oral contraceptive: synthetic estrogens and progestins, such as norgestimate and ethinyl estradiol (Ortho Tri-Cyclen).

Telomeres are directly correlated to the aging of a human body. Although some people might think that shorter telomere lengths are detrimental, the natural shortening of these telomeres are essential to healthy and normal aging. It is natural for cells to divide through mitosis, but each time cells are split telomeres are lost through the process. This is why the telomere maintenance system was evolved to protect the ends of chromosomes (Prescott, Kraft, & Chasman, 2011). Every time a cell is divided, its telomeres are weakened, and stress can accelerate this weakening, and biologically age the person. As a

These reactions will likely produce chronic inflammation, which is thought to contribute to many chronic, and terminal diseases such as alzheimer 's or cancer. This theory allows us to focus on the immune system, more specifically areas in which cells deteriorate or diversify too much. Once we are able to target which specific parts of the immune system causes it to deteriorate, cell repair potential is likely. If immune cell deterioration is due to diversification of human cells, one will one day be able to either slow the process or stop specific areas to allow the immune system to be strong and thus the likeliness of diseases such as alzheimer 's or diabetes will decrease. Another theory of aging is the Wear- and Tear Theory. This theory describes the aging process as the general deterioration of our body over time, whether it be environmental factors or just degeneration of our body 's structure and core. Like a car, over time we become less functional exposure to “radiation, toxins, and ultraviolet light can damage our genes,” as well as our own body 's functioning. Some nerve cells of the brain do not replicate or replace themselves as we age, so function will be lost as well. As our cells divide, it shortens the “telomeres of the chromosomes,” which will ultimately not be able to divide anymore as well. This theory allows one to understand the general

Modification of damaged DNA seems to be an understudied subject, there is much to understand on the restoration of DNA damage, repair and DNA methylation. Genomic DNA can be modified by methylation but much of it is affected on a gene when silenced. When epigenetic modification has been implicated with cancer and aging it causes DNA methylation to also have an impact on the double strand of DNA analysis. Modification as such provoke deteriorating changes like aging found in multicellular organisms and DNA damage may magnify biochemical pathways that regulate a cells growth or control DNA replication with DNA repair. In the article “DNA Damage, Homology-Directed Repair, and DNA Methylation” written by Concetta Cuozzo, Antonio Porcellini, Tiziana Angrisano, et al. they hypothesize how DNA damage and gene silencing may induce a DNA double-strand break within a genome as well as when DNA methylation is induced by homologous recombination that it may somewhat mark its reparation through a DNA segment and protect its cells against any unregulated gene expression that may be followed by DNA damage. The experiments used to demonstration how gene conversion can modify methylation pattern of repaired DNA and when that occurs methylation is able to silence the recombined gene. When exploring the molecular mechanisms that link DNA damage and the silencing gene then there is an induced double strand break that can be found at a specific location or DNA sequence in where the