Doxorubicin for Drug Delivery in Cancer Treatment

Doxorubicin for Drug Delivery in Cancer Treatment Jobin Baby Title – Nanoparticles (Doxorubicin) for drug delivery in cancer treatment Layman-friendly summary – My aim for this research is to eliminate all traditional treatment used for cancer treatment and introduce nanoparticles as new carrier for drug delivery for cancer treatments. Cancer treatments such as administering toxic drug through injecting/orally doesn’t specifically target cancerous cells but causing the toxic drug go through the bloodstream. This causes cell toxicity by diffusing toxic drug from the bloodstream to the cells. Nanoparticles coated with drugs that can be specifically targeted on to the desired cancer cell. Nanoparticles are small structures that is usually range from sizes between diameter 1-100 nm. Scientific summary – Nanoparticle enter the cell by receptor mediated endocytosis. Nanoparticle is engulfed/wrapped around by membrane a process called endocytosis. The interaction of the membrane and the nanocarriers allows for penetration of the cell by endocytosis. At time nanoparticle slip or penetrate in to the cell membrane and it adheres in to the cell. The nanoparticle containing the drug responds directly to the cell containing cancer and terminates it. Introduction – Cancer is the most dangerous disease. To treat cancerous cell toxic drugs are injected in to the blood stream to kill the cancer cell. But toxic drugs diffuse in to the cell from the bloodstream causing other cells to be toxic. So to minimize diseases/toxicity to other cell or cell membrane nanoparticles should be introduce. Nanoparticles attack on specific cells that causes cancer. Nanoparticles are used to reduce risk of toxicity and side effects of the drug. Doxorubicin nanoparticles binds to specific site of cancer cell and initiate/penetrates inside the cancer cell and breaks open to kill the cancerous cell. Nanoparticles have a relatively large surface which is able to bind, adsorb and carry other compounds such as drugs, probes and proteins (Wim H De Jong, 2008). Cancer is demonstrated as uncontrollable cell growth. Cancer starts when damaged or unused cells start too dived uncontrollably it grows in numbers or doubles so it’s impossible to stop when it spreads around t he body. To stop uncontrollable division of cancerous cell we should react faster. Administering using injection or orally the time taken to react to this cancerous cells is too late so, using nanoparticles its time efficient and its reacts directly with the cancerous cell. A drug is transported to the place of action, hence, its influence on vital tissues and undesirable side effects can be minimized (Wilczewska AZ, 2012). Nanoparticles are used for drug targeting. So, when reaching to the intended diseased/cancerous site in the body the drug carried in the nanoparticle needs to be released. So for drug delivery biodegradable nanoparticle formulations is needed as its intention is to release the drug and react to the cancerous cell. Nanoparticles and their payloads have also been favourably delivered into tumors by taking advantage of the pathophysiological conditions, such as the enhanced permeability and retention effect and the spatial variations in the pHà ¢Ã¢â€š ¬Ã¢â‚¬ ¦value (Dr. Tianmeng Sun, 2014). Various nanostructures like polymers, silicon and magnetic nanoparticles have been tested as carriers in drug delivery systems. Like polymers it uses this system where drug is coated on to the polymer and is administered form the mouth to react to the tumor cell. Polymer is a biodegradable substance. So it biodegrades as time goes on. It doesn’t stay in the body so it causes less damage to the cell cause cell toxicity is reduces. It is the same for nanoparticles it provides its function and then degrades causing no further toxicity to the cells. NPs can be used to safely and reliably deliver hydrophilic drugs, hydrophobic drugs, proteins, vaccines, and other biological macromolecules in the body. They can be specifically designed for targeted drug delivery to the brain, lungs, tumor cells and spleen (Singh, 2011). Methodology – Ten experimental rats containing cancerous cells kept under controlled condition Experimented on different rats with different stages of cancer The experiment was led under cleanroom because no contaminants enter and contradict the results. Nanoparticle (DOX) containing drug is placed on five rats Other five rats is undergone chemotherapy and its administered by injecting Every 24hrs results were recorded for 3 months Cell toxicity will be recorded by taking sample of blood from the rat every 48hrs The test subjects will be monitored for unusual behaviour for any side effects suffering from the nanoparticle injected in to the body or from the chemotherapy 4 hrs per chemotherapy was led. The treatment was led every three weeks for 3 months on rats. The lab and the result is checked by three competent authority After three months the rats under controlled environment will be checked for possibility of cancerous cell. If the results turned out as plausible, clinical trials is likely to happen. Grant chart – Expected outcomes – The outcome delivering nanoparticle containing the drug. A tumor marker is substance found in the body tissues that can be elevated only in cancer cells. Oncomarkers is the signature of a cancer cell and modern nanoparticles developed to conjugate to various molecular markers. Doxorubicin (DOX) is the most efficient anti-cancer drug. That’s why nanoscale capsule can deliver DOX only inside cancer cells using oncomarker signatures. It consists of a DNA-or origami shell covered by immune factors with molecular binding sites on its surface (Franà §ois Perreault, 2015). Nanoparticle delivery starts form bloodstream. DOX nanoparticles penetrate inside the cancer cell due to cancer markers on its surface. When nanocapsule conjugated with several markers its DNA-origami shell opens releasing DOX inside the cell. DOX successfully delivered. The cancer cell dies due to DOX direct delivery. So it’s expected using DOX direct delivery cancerous cell from the rats is eliminates/ter minated. DOX delivery will be expected to be faster and time efficient whereas chemotherapy will be slower. DOX delivery is expected to terminate cancerous cells but using chemotherapy it is expected that cancer cells is likely to be back or not all cancer cells are dead Budget – Staff salary 3 staff â‚ ¬21 per hour, 40 hrs in 2 weeks in a month so 6 weeks (240hr) in 3 months Per person â‚ ¬5040 3 person total â‚ ¬15,120 Clean room Clean room â‚ ¬18000 for 3months from February to March Total= â‚ ¬18000 Equipment Budget Malvern instrument â‚ ¬540 Nanosight analyser- â‚ ¬2750 Laboratories instrument â‚ ¬600 Total= â‚ ¬3890 Test Rats 10 Test rats â‚ ¬1000 each Total= â‚ ¬10000 Travel Budget â‚ ¬2000 travel expense for conference meeting in Boston Massachusetts Total â‚ ¬2000 Total budget needed = â‚ ¬49,010 Plans for dissemination – Once this research is completed this will be placed on scientific journal, newspapers, article and social media websites. This research will be approved to do clinical trials on real patients suffering from cancer. Scientific posters will be placed outside science conventions in Ireland and UK. A conference will be held on 27th September for science breakthrough and I will be presenting about my research and how it benefits in the future. Findings of my research will be presented on graphs and on excel to allow people to visualize my research. To spread news around hospitals, research will be published on local newspapers. Bibliography Dr. Tianmeng Sun, D. Y. (2014). Engineered Nanoparticles for Drug Delivery in Cancer Therapy. Angewandte Chemie International Edition, 12320–12364. Franà §ois Perreault, A. F. (2015). Environmental applications of graphene-based nanomaterials. Chemical Society Reviews. Singh, A. M. (2011). Biodegradable nanoparticles are excellent vehicle for site directed in-vivo delivery of drugs and vaccines. Journal of Nanobiotechnology, 9-55. Wilczewska AZ, N. K. (2012). Nanoparticles as drug delivery systems. 1020-1037. Wim H De Jong, P. J. (2008). Drug delivery and nanoparticles: Applications and hazards. Int J Nanomedicine, 133–149.

Shigella flexneri :: Medical Health Biology Essays

Shigella flexneri Shigella flexneri, a facultative anaerobe belonging to the family Enterobacteriaceae, is a Gram-negative rod that is the causative agent of diarrhea and dysentery in humans. Potentially life-threatening, S. flexneri's effects include bacteremia, hemolytic uremic syndrome (HUS) and toxic megacolon (4). The principle disease of diarrhea and dysentery caused by this pathogen is known as shigellosis. 10-100 organisms are sufficient to cause disease, and transmission is generally from person-to-person by way of fecal-oral (2). Shigellosis can be characterized as a disease with over 60% incidence in children ages 1-5 (6). Life cycle: S. flexneri causes infection via bacterial penetration of the mucous membrane in the human colon. Humans are the only known reservoir to this pathogen (7). Following invasion of M cells and upon contact with the epithelial cells of the colon, S. flexneri releases Ipa proteins through a type three secretion system. Once inside the host cell, Ipa proteins activate small GTPases in the Rho family as well as c-src, a protooncogene, leading to cytoskeletal rearrangements. This alteration to the cytoskeleton allows the bacteria to be macropinocytosed by the host cell. Once inside the host, the pathogen colonizes the cytoplasm. IcsA, a bacterial surface protein, activates the host protein N-WASP and, in turn, stimulates actin assembly by host Arp 2/3. Thus, S. flexneri develops actin-based motility enabling the pathogen to become efficient at cell-to-cell spread and host cell cytoplasmic colonization. Infected cells become highly proinflammatory and secrete IL-8. IL-8 attracts n eutrophils to the site of infection. The influx of neutrophils, chemokines and cytokines to the area damages the epithelial layer permeability and, in turn, advocates further S. flexneri invasion (6). Once initial invasion of S. flexneri occurs, the targeted epithelial cells require 45 minutes to 4 hours to mount an inflammatory response (8). A diagram outlining S. flexneri's type three secretion system can be viewed at: http://www.grad.ucl.ac.uk/comp/2003/jointposter/gallery/index.pht?entryID=29 Virulence: A 214-kb virulence plasmid encodes for S. flexneri's entry into human epithelial cells and intra-intercellular movement (6). Once in contact with the target cell, Ipa proteins (IpaB, IpaC and Ipa D) encode for a specific type III secretion system, thus, enabling entry of the pathogen into the target cell and characterizing S. flexneri with an invasive phenotype (1). One 30-kb block of the plasmid contains genes at the ipa/mxi-spa locus.

Calculating Ankle Joint Angular Kinematics Health And Social Care Essay

Kinematic information was obtained at 350Hz via an eight camera gesture analysis system as participants ran at 4.0ms-1+5 % , angles were created utilizing the coiling method and about XYZ, ZXY, XZY, YXZ, YZX and YXZ rotary motion cardan sequences.The consequences indicate that important scope of gesture chief effects were observed for the coronal and cross plane. Furthermore, it was besides observed that extremum angle chief effects were found for the coronal and cross planes. Post-hoc analyses revealed that ROM and extremum values utilizing the YXZ sequence and extremum values utilizing the ZXY sequence were significantly greater than the others.A popular method of quantifying the angular place of a stiff dynamic frame with regard to a mention frame is via the use of independent angles known normally as cardan or Euler angles ( Schace et al. , 2001 ) . Cardan/Euler rotary motions are obtained by agencies of an order sequence of rotary motions ( Schace et al. , 2001 ) . Rotations are considered to happen about the axis of the section co-ordniate system. For illustration during an XYZ cardan sequence of rotary motions, the section is rotated about the X axes by an angle A, so rotates about a revolved Y ‘ by an angle B and so eventually rotated about a twice rotated Z † axes by an angle C ( Scahce et al. , 2001 ) . For a given gesture, different cardan sequences can act upon the angular computations ( Cole et al. , 1993 ) . The International Society of Biomechanics ( ISB ) recommends that joint angles be calculated utilizing an XYZ sequence of rotary motions ( Wu and Cavanagh 1995 ) . However, the big sum of sagittal plane gesture during pace can encroach on the representation of motions outside the sagittal plane ( transverse talk ) , ensuing in greater than expected coronal/transverse plane articulation profiles ( Thewlis et al. , 2008 ) . As such it has been proposed that the XYZ sequence when applied to rotary motions outside the sagittal plane may non be the most appropriate method. A choice figure of probes have examined the influence that changing the sequence of rotary motions has on the representation of segmental kinematics ( Schace et al. , 2001, Kavaduna et al. , 2000, Tupling and Pierrynowski 1987 and Thewlis et al. , 2008 ) . However none of these probes have focused on the consequence that changing the sequence may hold on ankle joint kinematics. In add-on to the normally used method of Cardan angles, coiling angles ( Woltring et al. , 1985 ) can besides be used to depict joint gesture when projected on to a plane. The coiling method from a mention place is described in footings of rotary motion about and interlingual rendition along a individual line or axis in infinite ( Robertson et al. , 2004 ) . The ankle articulation plays a cardinal function in the stance stage pace rhythm. In combination with the hip and articulatio genus articulations the mortise joint facilitates motive power and transmits forces and minutes during the stance stage when the pes is regarded as the interface of the human locomotor system with the environment. Therefore, motion of the mortise joint is an of import constituent of pace mechanics and as such the right reading of its motion is indispensable in kinematic analyses. This survey investigated the influence of the coiling method every bit good as the 6 available cardan sequences on ankle joint kinematics in the sagittal, coronal and cross planes.MethodParticipants Eleven male participants volunteered to take portion in this probe ( age 19 + 1 old ages ; Height 176.5 + 5.2 centimeter ; Mass 78.4 + 9.0 kilogram ) . All were injury free at the clip of informations aggregation and completed an informed consent signifier. Ethical blessing for this undertaking was obtained from the School of Psychology moralss commission, University of Central Lancashire and each participant provided verbal consent. A statistical power analysis of pilot informations was conducted in order to cut down the likeliness of a type II mistake and find the minimal figure participants needed for this probe. It was found that the sample size was sufficient to supply more than 70 % statistical power in the experimental step. Procedure An eight camera gesture analysis system ( Qualisys Medical AB, Goteburg, Sweden ) captured kinematic informations at 350Hz from each participant running at 4.0ms-1. Velocity was controlled utilizing infrared photoelectric cells Newtest 300 ( Newtest, Oy Koulukatu 31 B 11 90100 Oulu Finland ) , a maximal divergence of + 5 % from the in agreement speed was allowed. Participants ran over a force platform ( Kistler, Kistler Instruments Ltd. , Alton, Hampshire, UK ; Model 9281CA ) , stance clip was determined as the clip over which 20N or greater of perpendicular force was applied to the force platform. The marker set used for the survey was based on the CAST technique ( Cappozo et al. , ( 1995 ) . Retro-reflective markers were attached to the 1st and 5th metatarsal caputs, median and sidelong maleoli, median and sidelong epicondyle of the thighbone, with a tracking bunch positioned on the right shank. A inactive test was captured to specify the pes and tibial sections. Kinematic parametric quantities were quantified utilizing Ocular 3-D ( C-Motion Inc, Gaithersburg, USA ) and filtered utilizing at 6 Hz utilizing a zero-lag low base on balls Butterworth 4th order filter following insertion with a maximal spread fill of 10 frames. Five tests of ankle joint rotary motion during stance were averaged for each participant. Angles were created about an XYZ, ZXY, XZY, YXZ, YZX and YXZ rotary motion cardan sequence referenced to organize systems about the proximal terminal of the section, where Ten is flexion-extension ; Y is ab-adduction and is Z is internal-external rotary motion. Statistical Analysis Descriptive statistics including agencies and standard divergences were calculated for each status. Differences in stance stage kinematic variables were examined utilizing perennial steps ANOVA ‘s with significance accepted at the P & A ; lt ; 0.05 degree. The Mauchly ‘s sphericalness premise was violated in all instances and as such the grades of freedom of the F statistic were adjusted via the Greenhouse Geisser rectification. The Shapiro-wilk statistic for each status confirmed that the informations were usually distributed. Appropriate post-hoc analyses were conducted utilizing a Bonferroni rectification to command for type I error. Effect sizes were calculated utilizing an Eta2. Cohen ‘s suggestion sing effects sizes was observed ( little R & A ; lt ; 0.3 ; medium R & A ; gt ; 0.3 and & A ; lt ; 0.5 ; big & A ; gt ; 0.5. All statistical processs were conducted utilizing SPSS 17.0.ConsequenceTables 1 and 2 present scopes of gesture and peak angles observed in al l three planes of rotary motion as a map of cardan sequence.Table1: Mean ( and standard divergence ) scope of gesture ( deg ) for each rotary motion as a map of cardan sequence ( * = important chief consequence ) n=11.Ten Yttrium Omega XYZ 27.94 + 10.34 5.62 + 3.86 4.67 + 3,21 XZY 26.75 + 11.35 5.29 + 5.13 5.88 + 4.52 YXZ 25.67 + 11.45 17.04 + 11.95 15.22 + 10.45 YZX 26.51 + 11.37 6.86 + 5.83 4.08 + 2.04 ZXY 26.38 + 10.12 15.96 + 27.51 28.78 + 11.73 ZYX 24.52 + 12.17 6.16 + 6.47 4.09 + 2.17 Coiling 25.45+8.64 5.26 + 6233 5.08 + 2.72 Main Effect**Table 2: Mean ( and standard divergence extremum values ) ( deg ) for each rotary motion as a map of cardan sequence ( * = important chief consequence ) n=11.Ten Yttrium Omega XYZ -87.65 + 3.83 -11.04 + 5.48 -2.14 + 4.53 XZY -87.70 + 3.57 -11.15 + 5.46 0.21 + 4.78 YXZ -84.07 + 5.05 -68.25 + 24.29 -71.01 + 20.91 YZX -87.64 + 3.68 1.00 + 4.97 -11.71 + 4.80 ZXY -87.7 + 3.66 1.07 + 20.47 -1.42 + 13.41 ZYX -84.6 + 3.75 -3.18 + 4.88 -11.78 + 4.81 Coiling -87.75 + 2.40 -7.40 + 7.68 -11.91 + 3.27 Main Effect**The consequences indicate that important scope of gesture chief effects were observed for the coronal F ( 1.85, 16.66 ) = 10.04, P & A ; lt ; 0.05, eta2= 0.53 and cross plane F ( 2.04, 18.39 ) =21.91, P & A ; lt ; 0.05, eta2=0.71. Post-hoc analyses revealed that both coronal and cross plane ROM utilizing the YXZ and ZXY sequences was significantly greater than the others. Furthermore, it was besides observed that extremum angle chief effects were found for the coronal F ( 2.28, 20.48 ) = 82.99, P & A ; lt ; 0.05, eta2=0.90 and transverse planes F ( 2.08, 18.72 ) = 80.49, P & A ; lt ; 0.05, eta2= 0.90. Post-hoc analyses revealed that peak coronal and cross plane angles utilizing the YXZ sequence were significantly greater than the others.Figure 1: Ankle joint kinematics in the sagittal, coronal and cross planes as a map of cardan sequence ( XYZ= black, XZY= red, YXZ=yellow, YZX=blue, ZXY= cyan, ZYX=green and Helical =purple.DiscussionEuler/Cardan angles are used extensive ly within the Fieldss of clinical and sport biomechanics. However, the consequence of changing the sequence of rotary motions has yet to be investigated with regard to the ankle articulation composite. The consequences indicate that changing the sequence of rotary motions when detecting kinematics in the sagittal plane has no important affect on joint scope of gesture parametric quantities. This is unsurprising given the laterality of sagittal plane gesture at the mortise joint during pace. Leading to the decision that choosing the appropriate sequence of rotary motions is non an issue when look intoing kinematics in the sagittal plane. However, for the coronal and cross planes a important consequence was found in footings of both the scope of gesture and peak angle observed during the stance stage. The consequences of this survey with regard to the mortise joint articulation found that the ZXY and YXZ sequences significantly affected ankle joint kinematics bring forthing highly big values for both scope of gesture and peak angles. The mistake associated with these sequences is such that the kinematic estimations are anatomically unrealistic. It is interesting to observe that the two combinations which were observed to be significantly different from the others ( YXZ and ZXY ) each had X 2nd in the order of rotary motions. This was the instance even when the principal axis under probe is placed foremost ( i.e. ZXY when detecting transverse plane rotary motion and YXZ when detecting coronal plane rotary motion ) , where one would presume that the comparative orientation could non be affected by the grade of sagittal plane gesture holding been placed after it in the sequence. It appears based on these consequences that the ISB recommendations are appropriate for the representation of ankle joint kinematics and as such its usage is encouraged, as it will let comparing of future research trying to quantify ankle joint gesture performed by different research workers. In add-on the consequences suggest that the YXZ and ZXY sequences produce the greatest mistake and therefore the use of these sequences to quantify ankle gesture outside the sagittal plane is strongly discouraged. This survey emphasizes the demand for methods leting joint kinematics to be measured accurately. Therefore, guaranting joint map is represented right.

Spread of Buddhism in China Essay - 773 Words

It is believed that Buddhism spread to China through the Silk Road. When the Silk Road opened in the 2nd century BC, missionaries and pilgrims spread Buddhism to China. Chang Ch’ien was recorded to first bring Buddhism to China when he heard about India and Buddhist beliefs on his way back to China. In about the 1st century BC, a Buddhist community is said to have been living in China. But the most well-known story of the spreading of Buddhism is when Han emperor, Mingdi, had a dream about Buddha in 68 CE and sent Cai Yin, his official to learn more about it. Meanwhile, Mingdi learned from his ministers that he had seen Buddha, â€Å"the God of the West† in his dream. After 3 years Cai Yin came back to china with Buddhist teachings and†¦show more content†¦Starting in 468 BCE during the Zhou dynasty, the Grand Canal took about 6 million peasants about a millennium to build. The construction of this canal finally finished in 610 CE under Emperor Yangdi of the Sui dynasty. Changing China’s staple from millet and wheat to rice was the main reason of the building of the canal, but it also helped Chinese economy by connecting the more productive southern China to the capitals in northern china. It increased interdependence between the north and the south. One section of the Grand Canal was also intended to supply Chinese armies which led to better defense and administration in China. Also, in building the canal, officials were required to work together, so the Grand Canal brought better authority and unity to political officials. The downside of this canal, though, was the number of peasants killed in constructing it. Over half of the 6 million peasants employed to build the canal died in building it, which was a reason the Sui dynasty fell. The great Grand Canal set the foundation for the great Tang dynasty. Empress Wu Zetian, the only woman to rule China, ruled during the Tang dynasty, but exerted cruel and malicious met hods to gain power. She was born with the name Wu Zhao into a wealthy family and learned to write, read, and play music. Because of her beauty and intelligence, Wu became Emperor Tsung’s fifth favorite concubine, orShow MoreRelatedSpread of Buddhism in China834 Words   |  3 Pages Buddhism arrived in China by the first century C.E. by way of the Silk Road. Initially, the spread of Buddhism was met with positivity, but as the centuries passed, the Chinese began to view it in a negative light. Additionally, during a period of disunity and political instability, the Chinese peasants welcomed Buddhism, but as Buddhism became more popular, Chinese aristocracy and government saw it as a threat to their power and moved to discredit its movement. 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