Evaluate And Analyze The Paper I.E. Any Improvements, Why Things were done In the Relative Manner
Cibely, O., Olivan, M., Jochen Springer, S. B., Tshiner, A., Figueras, M., & Toledo, M. (2012). Theophylline is able to partially revert cachexia in tumour bearing rats. Nutrition and metabolism.
Introduction/background
Explain the background to the research and how it came to being, name any previous articles used as the basis and explain why they are important, is the article building on previous work or aiming to resolve disagreements in previous studies, state the hypothesis being tested, what is the importance of the research question?
Cibely et al. (2012) wrote the article of interest. The background that led to the writing of the paper revolves around research done on cancer cachexia as one of the most popular manifestations of malignant disease in its advanced stage. The research team conducted statically research on the numbers of individuals suffering from terminal cancer and had this complication. It noted that 22% of all cancer deaths are caused by cachexia. The background information is valid, as it goes ahead to list other abnormalities associated with the form of cancer. The exploration divulges to the reader the expected aspects of the underlying ailment in relation to the research.
The background on the research goes ahead to elaborate other effects of cachexia inclusive of the areas of the body it affects the most. In elaborative terms, the depletion of lean body mass is the predominant symptom. It extends from skeletal muscle to cardiac proteins, which adversely affects the performance of the heat. The research team also noted that there had been researching done on means of treating the symptom.
It highlights how tumors of cancer increase the level of fragmentation of the DNA in skeletal muscle in both rats and mice, which is added to the developing degradation of muscle protein. Further research indicated that the activation of proteolysis catalyzes the loss of muscle tissue. The first Inquisition falls into place here, as they indicated that there is little research on the means by which intercellular proteins are broken done albeit noting that the location of the process, which is around lysosomes, is known.
As such, a notable point was discovered in the study of ATP-ubiquitin-dependent proteolysis system. It has been shown to have influences on the metabolism of protein about a couple of pathophysiological complications such as heart failure, infections, and cancer. The researchers were noted that when the conditions are involved, whenever the wasting of muscles happens, the resultant condition is cachexia.
As such, the problem the existing therapeutic solutions applied in the reduction of wasting muscles have not been successful, and it is due in large part to the contamination from the inhibitors that strain the ubiquitin-dependent proteolytic system. The research team sought to add to the existing literature by testing a new treatment. The substance is elaborated, inclusive of a short background that justifies why it is used in the research experiment.
The drug in question is theophylline. It is a known alkaloid that is group together with theobromine and caffeine it exists in chocolate and tea leaves which a characteristic relaxing effect on the manner with which peripheral blood vessels dilate and even bronchial muscles. The research team also offers areas where it has been used as a form of treatment, namely in patients with chronic obstructive pulmonary disease and asthma.
Not only that, theophylline, according to the article is known for increasing the amount and expression of the gene PPAR-y and as such, shows potential in instilling an anti-inflammatory effect. Therefore, the research team sought to inquire answers to the question, “can theophylline be used as a dependable treatment for muscle wasting?” the research team attempted to find out whether the anti-wasting entities of theophylline have a positive effect on rat models of cachexia cancer cells.
The research team put a point of note across, on how they have already investigated the ophulline treatment effects in a hypanthium model in a theoretical perspective. The model provides a structure to guide the analysis of anti proteolytic capabilities of medicines used to stop the wasting of muscles. In the practical research, the test subjects were rats with tumors that showed a high level of wasting of muscle showing the presence of cachexia.
The research program encompassed in the article seeks to add to the literature about the treatment of muscle wasting in patients affected by cancer cachexia. The only previous research referred to in the program was conducted by themselves, as a leading part of the research program at hand. The question asked aims to solve the challenges about the current treatments. A significant number of them show little or adverse effects on the patients and as such, creating a gap in the medical knowhow on how to treat this disease.
Methods, Statistical Principles and Design
Explain the general design of the experiment and why it is ideal for addressing the hypothesis.
Evaluate strengths and weaknesses of the design (look at the discussion section of the article for assistance).
Evaluate decisions made in the design of the experiment such as length of treatment, dose used, choice of patients, number of patients etc.
Explain the techniques used inclusive of statistical methods and why they are significant, do not be excessive and repetitive, critically review the methodology and research design.
The research program is a practical one, involving the collection of information from case studies and analyzing it. The type of information collected in such studies is primary in type. In these type of research programs, the question bases the type of information to be obtained with the hypothesis forming a guideline to the expected results. Due to the medical nature of the subject at hand, the research team needed to retrieve specialized tools to take the relevant data as well as conduct the various results.
The use of animals can be a delicate issue and more specifically, an ethical one. The research team is seen to consider this and obtains the relevant permissions to conduct the test. The mouse skeletal cells were of the C212 type obtained from the American Type Culture Collection. The samples were done with high glucose Dulbecco’s modified Eagles medium. It was supplemented with 10% fetal bovine serum, penicillin measuring at 100 U/ml, L-glutamine measured at 2mm and sodium pyruvate.
The medium for the concoction was changed to DMEM that was altered with 10% horse serum to induce the differences of the genetically manipulated cells. To monitor the high frequency of myotube formation, the research team used a microscope. The scenario was noted to occur after the fourth day. The fused myotube cultures were valid for experimental purposes after five days.
The methodology was subdivided into several categories dependent on the hypothesis. The first is the application of the hyperthermia model in the analysis of protein degradation quantities. In this segment, the samples of myotubes were labeled based on phenyl nine, were washed substantially with PBS as well as an incubation period at a predefined temperature, and was stopped when the forms of radioactivity present. Rinsing of the samples was done again and incubated with varying concentrations of theophylline, a process that has been used by Smith & Tisdale (2005).
On the sampling of the animal samples, the male Wister rats were preferred. They were mentioned in a structured light and dark duration and were regularly fed on a daily basis. The European Community provided guidelines on how to manipulate the animal samples ethically. The research team ensured that the parameters concerning animal treatment were legal through the acquisition of permission of both the Generalitat de Catalunya Ethics Committees as well as the University of Barcelona.
The third category of the methodology was the treatment and inoculation of the tumor. The corresponding rats were classified into two categories. These groups were labeled as tumor and control hosts. The group of tumor mice was injected with an intraperitoneal inoculum of Yoshida ascites haematoma cells that were retrieved from tumors with an elevated phase regarding growth. The tumor rats were subdivided into the untreated and treated samples. The related group was continuously treated with doses of intragastric theophylline. Once a week, the mice infected with a tumor. These samples indicated a substantial level of cachexia coupled with the loss of weight. Sections of the tumor were retrieved from the peritoneal cavity for the quantification of the number and volume of cells.
The means of analyzing the composition of the rat’s bodies formed another category of sourcing data. According to the research, a nuclear magnetic resonance spectroscopy device was utilized. It was the ideal tool to analysis the composition of the tissue samples regarding reactions to muscle, fat and body fluids that were not from tissue.
Using several of the tissues components provided varying radio pulses, signals, and frequencies in an elaborate static magnetic field. The use of radio pulses was selected as they catalyze a change of hydrogen nuclei exposed to polarization in a magnetic field. The type of expected changes is relaxing scenarios that varied in times of relaxation based on the composition of the substance. The device used monitors these relaxation times with the range being determined by the quantity and type of tissue component being tested.
Another category of the methodology is the study of echocardiography readings. The temperature of the sampled rats was monitored after they were connected to ECG electrodes in a supine position, for controlling the heart rate and anesthetized through the injection of 1.5% isoflurane. Notable symptoms included the loss of hair. The echocardiography tool selected was of high resolution with the parameters of interest being observed using M-mode. These parameters were inclusive of the enlargement of the thickness of the intraventricular septum, the diameter of the left ventricle, and the thickness of the posterior wall.
In addition, the end-systolic volume and the Lv end-diastolic volumes were analyzed in B mode. The difference in modes was meant to compensate for the consideration of any observable changes in the geometry of the ventricular (Cibely et al., 2012).
The echocardiography exercise was executed 24 hours before starting the treatment. The RNA quantity in the soleus and heart muscles was analyzed and extracted using the TriPureTM kit. It is an improvement in the acid guanidium phenol commercialized method. The substantial analysis also encompassed analysis of real-time polymerase reactions with the use of the cDNA synthesis tool. Pimers used to elaborate the various levels of mRNA were custom designed to detect predefined products from genes.
The information collected was predominantly numerical in nature with an expectation of comparative analysis to be done in elaborating the primary data collected. The statistical analysis encompassed two key calculations, namely, one-way and two-way analysis of variance. The research exercise was subdivided into critical categories, all aimed at providing a complete analysis of the effects of the proposed drug.
The hypothesis sought to test the possible reduction of muscle waste through the introduction of theophylline. The substance was tested on cell culture, direct introduction to the tumor, the level of protein degradation and the overall physiological body reactions of the samples to the substance. The use of primary data enabled the research team to conduct fresh studies of the application of the drug, which proved to be a dependable solution, as the results obtained were not from previous studies. It made the recommendations provided to bring a fresh perspective to the treatment of cancer cachexia.
The use of avid measuring tools bolstered the accuracy of the results. Not only did the research team identify the areas of study, select dependable samples from the appropriate authorizes but used the correct tools as well. The choice to use animal testing samples was an advantage as well. It is because of the non-curability of the disease at hand.
The research team sought to provide a new means of managing the symptoms and not to cure it. As such, the infected animals did not have dire consequences such as the loss of human life, which is considered illegal in comparison to that of animals. The research team is careful in its selection of analysis methods. The use of a predefined model of hyperthermia provided a guideline to test the proteolytic modulatory capabilities of theophylline.
Results and Discussion
The research program posted that there is a significant association between hearing complications and cancer deaths. It posts as a matter of fact that these estimations may be even bigger as when further analysis of these types of deaths is found, revelations such as toxic infections, drug overdoses and imbalance of osmotic measures are discovered, indicating that there is a worrying number of heart alterations that occur while cancer patients are seeking treatment.
The research team forwards a worrying statistic of how close to half of myeloma patients with multiple complications have experienced some form of cardiac failure during the neoplastic process. An indicated by the results of the study, the rats that had tumors implanted in them posted a reduction in the size of their hearts. Further observations indicate that an increase in the consumption of oxygen with regards to hearing function in the experimental models of cancer.
Some of the outstanding structural changes encompassed a rise in the mitochondria and sarcomere ratio alterations, just as seen in cardiac failure incidences. It formed part of the resolve to use the experimental rat model to analyze parameters of the heart and more suitably, the effect theophylline has on cardiac mass. Among other observable results was the reduction of the size of the thickness of the posterior wall where the tumor was implanted. It was concluded that it was connected with the reduction of the mass of the left ventricle.
The research program concludes with substantial support for the use of theophylline in the reduction of muscle wasting away resulting from cancer, especially those that affect cardiac muscle. It notes that there are no therapeutic approaches that are a guaranteed solution when it comes to the treatment of cancer. The team recommends that it is not ideal to use a single drug in the treatment of muscle waste.
The researchers used of various combinations of select traceutical that have a high concentration of protein nutrition provide a dependable multifactorial solution for now. These of theophylline can be depended on upon, provided it is combined with other nutritional medicines. It emphasizes on the further research on the anti-wasting effects of the substance when combined with other drugs of similar nature.
Briefly, the research is comprehensively articulated. It presents the issue at hand, provides a background on the information and condition that led to the composition of the research program. The methodology used is ideal for the type of information that centers the research program. The use of statistical methods to elaborate primary data collected from laboratory experiments is the best means to develop the numerical information provided.
References
Cibely, O., Olivan, M., Jochen Springer, S. B., Tshiner, A., Figueras, M., & Toledo, M. (2012). Theophylline is able to partially revert cachexia in tumour bearing rats. Nutrition and metabolism.
Smith, H., & Tisdale, J. (2005). Donwregualtion of ubiquitin depdent protein degradation in nurine myotubes druing hyperthermias by eicosapentaenoic acid. Biochemisty and biohpysiology Community, 340-351.
