Mark Corson

By Q. Sancho. Missouri Baptist College.

Scientific community worldwide has been working toward discovering “nanoscale” solutions to treat these diseases by using nanoparticle-based drug delivery systems buy coumadin 1 mg overnight delivery. The applications of such sys- tems for cancer treatment are discussed in the following sections buy 2 mg coumadin amex. Surgical treatment (excision of the tumor) is usually the first choice of treatment preferred by physi- cians cheap coumadin 1mg with mastercard. However, surgical excision is not effective when the cancer cells have infil- trated the nearby vital organs or have spread to distant parts of the body (metas- tasis). Cryosurgery is another surgical technique that is used for freezing and killing the tumor cells. It is an alternative to surgical excision and is used to treat tumors that have not spread to distant organs and for the treatment of precancerous or noncancerous lesions. Chemother- apeutic drugs may destroy healthy tissue along with cancer cells and carcinoma- tous tissue (cytotoxicity). The cytotoxic effect of chemotherapeutic drugs is highest in bone marrow, gonads, hair follicles, and digestive tract, all of which contain rapidly proliferating cells. The adverse effects of chemotherapy include fatigue, nausea, vomiting, alopecia (loss of hair), gastrointestinal disturbance, impaired fer- tility, impaired ovarian function, and bone marrow suppression resulting in ane- mia, leucopenia, and thrombocytopenia (3,4). Another technique of cancer treat- ment is radiation therapy, which uses radiation energy to destroy cancer cells and reduce the size of tumors. Bone marrow transplantation and peripheral blood stem cell transplantation are done to restore stem cells that are destroyed by high doses of radiation or chemotherapy. Recent research work has been focused on studying gene therapy for cancer treatment. Gene therapy is an experimental treatment that involves introducing genetic material into the cancer cells to destroy the cells (6). Angiogen- esis plays an important role in the growth and spread of cancer cells (7). New blood vessels act as a source of oxygen and nutrients to the cancer cells, allowing these cells to grow, invade nearby tissue, spread to other parts of human body, and form new colonies of cancer cells. Angiogenesis inhibitors are used to prevent the for- mation of blood vessels, thereby depleting the cancer cells of oxygen and nutrients. Hyperthermia (also called thermal therapy or thermotherapy) is a type of cancer treatment technique in which the cancer cells are exposed to high temperatures (up to 113◦F). Research has shown that high temperatures can damage and kill cancer cells with minimal injury to normal tissues (8). By damaging proteins and func- tional structures within cells, hyperthermia destroys cancer cells (9). Hyperthermia may make some cancer cells more sensitive to radiation or harm other cancer cells that radiation cannot damage. Thus, it is almost used with other forms of cancer therapy, such as radiation and chemotherapy (10). Laser therapy is most commonly used to treat super- ficial tumors on the surface of the body or the lining of internal organs. Photody- namic therapy is a type of cancer treatment that uses a drug called a photosensitizer or photosensitizing agent (12). When photosensitizers are exposed to this specific wavelength, they produce singlet oxygen, which destroys cancer cells. Targeted cancer therapy uses target-specific drugs that invade cancer cells and block the growth and metasta- sis of cancer cells by interfering with specific molecules involved in carcinogenesis and tumor growth (13). To overcome the disadvantages of current cancer treatment techniques, the scientific community has turned toward nanotechnology to develop newer and more effective drug carrier systems to safely shepherd the anticancer drugs to the cancer cells. Examples of drugs in this class include methotrexate, fluorouracil, hydroxyurea, and mercaptopurine. A few examples of drugs in this class include cisplatin and antibiotics such as daunorubicin, doxorubicin, and etoposide. Disruption of Synthesis or Breakdown of Mitotic Spindles Mitotic spindles serve as molecular railroads with “north and south poles” in the cell when it starts to divide. These drugs disrupt the formation of these spindles and therefore interrupt cell division. Classic examples of drugs in this class of mitotic disrupters include vinblastine, vincristine, and paclitaxel. The applications of nanoparticles as carriers for these anticancer drugs are discussed in the following sections. Results of numerous scientific research studies done in nanotech- nology and nanomedicine are inspiring the scientific community to discover new, innovative, noninvasive tools at the nanoscale level for such purposes. Nanoscale cantilevers (15) and quantum dots (16,17) are being studied as cancer detection tools at the cellular level. If the tumor has not been detected in its early stage, treatment methods should be devised to eradicate the fully developed cancer cells without harming the normal, healthy cells of human body. The various types of nanoparticles that are currently studied for their use as drug delivery systems are polymeric micelles, magnetic nanoparticles, colloidal gold nanoparticles, and ceramic nanoparticles (18–20). These nanoparticulate-based drug delivery systems can be characterized for their localization in tumor cells by coating them with tumor-specific antibodies, peptides, sugars, hormones, and anticarcinogenic drugs. These nanoparticles have been effectively coupled with the abovementioned anti- carcinogenic chemotherapeutic agents and have been tested for their target speci- ficity. These nanoparticles are superior over conventionally available drug delivery systems, as the chemotherapeutic agents can be targeted to a specified area of the human body by adding nanoscale surface receptors. These receptors specifically recognize the target tissue and bind to it and release the drug molecules (21). Drugs can also be pro- tected from degradation by encapsulating them with nanoparticle coatings (22). As nanoparticles are extremely small, they can penetrate through smaller capillaries and are easily taken up by cancer cells.

Today the problem of onychomycosis is urgent order 2mg coumadin free shipping, due to the prevalence of onychomycosis in the population and their high contagiousness buy coumadin 5mg on-line. According to epidemiological data onychomycosis incidence is 20% of the population and 50-70% in the structure of fungal diseases cheap coumadin 1mg online. Onychomycosis – is a generic term that refers to fungal infection of nails feet and hands, caused dermatophyte, mold fungi. The most common causative agents of disease are fungi of the genus Trichophyton, Candida and Epidermophyton. To study the basic aspects of epidemiology, etiology, pathogenesis, clinical manifestations and modern pharmacotherapy for onychomycosis. The analysis of foreign literature, modern domestic and foreign standards of care for patients with onychomycosis. The main clinical symptoms of onychomycosis are changes in color, shape of the nail due to subungual hyperkeratosis and destruction of the nail plate. For the diagnosis of onychomycosis used bacterioscopic and bacteriological methods. Modern pharmacotherapy for onychomycosis includes systemic and topical antifungal therapy. Topical therapy may only be apply in case of damage of less than 30% of the nail plate in the absence or low hyperkeratosis, contraindications to systemic therapy. Local antifungal therapy include using of keratolytics for lysis of the affected nail plate from the nail bed, followed by treatment antifungals for topical use. There form of drugs for the topical application are lacquer, cream, ointment, containing ketoconazole, terbinafine, oxiconazole, miconazole, and undecylenic acid. Systemic antifungal therapy is required to shown at the defeat of more than 50% of the nail plate, a 2-3 defeat of the nail plate, nail plate pronounced changes (hyperkeratosis, onycholysis), the defeat of the nail matrix. Among the antifungal drugs for systemic use recommended ketoconazole, itraconazole, fluconazole, terbinafine. Duration of pharmacotherapy is determined by the severity and nature of the disease, the average course of treatment is 6-12 weeks, sometimes more. Itraconazole administered 200 mg two times a day for 7 days and after 3 weeks of rest. It recommended in the defeat nail plates hands – 2 courses, nail plates feet – 3 courses of pulse therapy. Modern pharmacotherapy for onychomycosis includes combination topical and systemic antifungal drugs. System reaction to stress, which is aimed at eliminating or mitigating negative effects, is accompanied by changes in behavior, autonomic, motor, sensory and other body functions. Behavior stress is an integral part of the overall behavior, thus changing behavioral reactions leads to inhibition of the central nervous system. The purpose of this work was to study the effect of oligopeptides derivatives on behavioral responses of rats in the "open field" test. Investigated substances were administered orally in the form of aqueous solutions in doses of 70 and 100 mg/kg in 60 minutes before the experiment start. The animals of control group were injected with the corresponding volume of saline. The study found that the number of crossed squares was significantly increased after the administration of compound 2 at a dose of 70 mg/kg by 72. The administration of the compounds was affected to the number of explored holes as follows: compound 1 at a dose of 100 mg/kg, compound 2 at a dose of 70 mg/kg, compound 5 at a dose of 100 mg/kg increased the index by 88. During the study it was found that the greatest influence on the behavior of rats, such as psycho-stimulant activity, showed the compound 6 which increased the number of crossed squares in 2 times at a dose of 100 mg / kg, the number of vertical racks in 1,7 times, and the number of explored holes in 1. The administration of the same compound at a dose of 70 mg/kg influenced the behavior of experimental animals such as the number of crossed squares increased by 64. Among the seven oligopeptides derivatives all substances are characterized by psycho-stimulant activity at a dose of 100 mg/kg. Cough – a natural reflex defensive reaction that occurs in response to any irritation airway inflammation or something that prevents the passage of air for pneumatic paths. Despite the fact that the cough reflex is natural in our body which main function - cleansing the respiratory tract and restore their patency, severe cough can significantly reduce the quality of life of any person. Drug for the treatment of cough should be safe and highly effective to the patient in a very short time deprived of this disease. Ledum palustre - evergreen shrub heather family (Ericaceae), which includes essential oil (1. In modern medical practice, Ledum palustre is used as an antitussive and expectorant. We have been set up an experiment- cough model in rats induced with citric acid in the vivarium at the Institute of Microbiology and Immunology I. The experiment involved rats weighing 200-250 g rat was placed in a box, which has been connecting to the nebuliser and inhaled citric acid 10% for 5 minutes. In the first stage the animals individually tested for reaction intensity citric acid per day prior to administration of the test substance. The experience collected intense coughing rats (15-25 cough attacks within 30 minutes). In the second step (the next day) experienced reference drug codeine (20 mg / kg) which was administered orally through a metal probe 60 minutes before the inhalation of 10% citric acid for 5 minutes. The study gave a positive result- after the introduction of caffeine coughing attacks decreased on 79%. The stated cough model makes it possible to study the antitussive activity and dose dependence of extracts Ledum palustre. To reset the rhythm to sinus rhythm using cardioversion, which can be conduct in two ways: electrical cardioversion or cardioversion with drugs.

Drugs used in the treatment of leprosy should always be used in combinaton; this is essental to prevent the emergence of resistance generic 5mg coumadin overnight delivery. Lepra reactons are episodes of sudden increase in the actvity of leprosy and are ofen accompanied by neurits; reactons must always be treated promptly to prevent permanent nerve damage and disability 5mg coumadin free shipping. Leprosy multdrug therapy should contnue during a lepra reacton without interrupton generic coumadin 2mg amex. If there is no nerve damage, type 1 reactons may be treated with analgesics such as acetylsalicylic acid or para- cetamol. If there is nerve involvement cortcosteroids, such as oral prednisolone should be used in additon to analgesics. Therapy for type 2 reactons may include analgesics, such as acetylsalicylic acid or paracetamol and a cortcosteroid, such as oral prednisolone. Severe type 2 lepra reactons should be treated under medical supervision in hospital. If a patent does not respond to lepra reacton treatment within 6 weeks or seems to become worse, the patent must be sent immediately to the nearest specialist centre. It can be successfully treated with a 12-week course of oral pred- nisolone; if patents do not respond, specialist centre treat- ment is required. Treatment Regimens: The recommended regimen for paucibacillary leprosy in adults (50-70 kg) is rifampicin 600 mg once monthly and dapsone 100 mg daily. Children aged 10-14 years may be given rifampicin 450 mg once monthly and dapsone 50 mg daily. Children aged 10-14 years may be given rifampicin 450 mg and clofazimine 150 mg, both once a month together with clofazimine 50 mg every other day and dapsone 50 mg daily. For example, dapsone 25 mg daily, clofazimine 50 mg twice a week and clofazimine 100 mg and rifampicin 300 mg once a month. Precautons Pre-existing gastrointestinal symptoms (reduce dose, increase dose interval or discontinue if symptoms develop during treatment); liver and renal impairment; may discolour soft contact lenses; paediatrics, elderly, interactions (Appendix 6d). Adverse Efects Reversible discolouraton of skin, hair, cornea, conjunctva, tears, sweat, sputum, faeces and urine; dose-related gastrointestnal symptoms including pain, nausea, vomitng and diarrhoea; severe mucosal and submucosal oedema, with prolonged treatment with high doses-may be severe enough to cause subacute small-bowel obstructon (see also Precautons); pruritus, ichthyosis, elevated blood sugar, diminished vision, dizziness, eosinophillic enteropathy. Dermatts herpetformis: start with 50 mg daily and increase up to 400 mg tll full response is obtained; dose reduced to minimum maintenance level as soon as possible. Child- 1 to 2 mg/kg body weight as minimum dose to start with, increased weekly so that at the end of 7th week patent is receiving max. On long-term treatment patents and their caretakers should be told how to recognize blood disorders and advised to seek immediate medical atenton if symptoms such as fever, sore throat, rash, mouth ulcers, purpura, bruising or bleeding develop. Adverse Efects Haemolysis and methaemoglobinaemia; allergic dermatts (rarely, including toxic epidermal necrolysis and the Stevens-John- son syndrome); rarely, hepatts and agranu- locytosis; ‘dapsone syndrome’ resembling mononucleosis-rare hypersensitvity reac- ton with symptoms including rash, fever, jaundice and eosinophilia; gastrointestnal irritaton; tachycardia, headache, nervous- ness, insomnia, blurred vision, paraesthe- sia, reversible peripheral neuropathy and psychoses reported; increase in retculo- cytes, vertgo; pancreatts; renal papillary necrosis; anorexia. Contraindicatons Hypersensitvity; jaundice; patents with earlier drug induced liver disease. Precautons Reduce dose in hepatc impairment (Appendix 7a); liver functon tests and blood counts required in liver disorders, alcohol dependency, elderly and on prolonged therapy; renal impairment (if dose above 600 mg daily); lactaton; porphyria; discolours sof contact lenses; advise patents on oral contraceptves to use additonal means; interactons (Appendix 6b, 6c, 6d); pregnancy (Appendix 7c). Note: Resumpton of rifampicin treatment afer a long interval may cause serious immunological reactons, resultng in renal impairment, haemolysis, or thrombocytopenia-discontnue permanently if serious adverse efects occur Patents or their caretakers should be told how to recognize signs of liver disorders and advised to discontnue treatment and seek immediate medical atenton if symptoms such as persistent nausea, vomitng, malaise or jaundice develop. Adverse Efects Severe gastrointestnal disturbances including anorexia, nausea, vomitng and diarrhoea (antbiotc-associated colits reported); headache, drowsiness; rashes, fever, infuenza-like syndrome and respiratory symptoms, collapse, shock, haemolytc anaemia, acute renal failure and thrombocytopenic purpura-m ore frequent with intermitent therapy; alteratons of liver functon-jaundice and potentally fatal hepatts (dose-related, do not exceed max. Infecton is usually due to inhalaton of infected droplet nuclei with the lung generally being the frst organ afected, but the primary infecton is usually asymptomatc. Infec- ton and infammatory responses resolve with the develop- ment of acquired immunity. Surviving bacteria may become dormant or in susceptble patents, progress to actve primary disease; dormant organisms may produce disease and this ofen occurs if immune status is altered. Tuberculosis is the most prevalent infectous disease of adults and causes 26% of avoidable adult deaths in the developing world. The increase in resistant strains and poor compliance of dosage regimen which may contribute to resistance and treatment failure has led to the development of regimens with directly super- vised treatment. Simplifed drug regimens and intermitent therapy have been introduced to improve compliance. If a patent receiving a twice weekly regimen misses a dose of tablets, the missed dose represents a bigger fracton of the total number of treat- ment doses than if the patent was receiving a three tmes weekly or daily dose regimen. Therefore, there is a greater risk of treatment failure with twice weekly regimens. Fixed- dose combinaton tablets incorporatng 2 or more drugs are also used to improve compliance and decrease medicaton errors; they should be used unless one of the components cannot be given because of resistance or intolerance. The inital phase (2 months) involves the concurrent use of at least 3 drugs to reduce the bacterial populaton rapidly and prevent drug-resistant bacteria emerging. The second contnuaton phase (4-6 months) involves fewer drugs and is used to eliminate any remaining bacteria and prevent recur- rence. Direct observaton of therapy is considered essental to ensure compliance in the inital phase and also useful in the contnuaton phase if patents are receiving rifampicin. Unsupervised and alternatve regimens as set out in the following tables may be administered as specifed. Chemoprophylaxis with isoniazid can prevent the devel- opment of clinically apparent disease in persons in close contact with infectous patents and also prevent the reac- tvaton of previously dormant disease in other persons at high risk partcularly those who are immunodefcient. Dose Intramuscular or intravenous injecton or infusion Adult- 15 mg/kg body weight daily in two divided doses, increased to 22. Neonates- loading dose is 10 mg/kg body weight followed by 15 mg/kg body weight in two divided doses.

Modern graph mining algorithms such as the ones described below cheap 1mg coumadin otc, work in a depth-first manner order coumadin 2mg online. There are three problems central to frequent subgraph mining; the difference between algorithms lies in how they address these problems purchase 5mg coumadin fast delivery. First, as was mentioned, subgraph isomorphism tests are expensive in terms of computation steps needed to perform the search. Third, since generated duplicates require isomorphism tests, their number should be kept to a minimum, e. All embeddings are stored and used for isomorphism testing and for restriction of fragment extensions to refinements that actually exist in the database. To reduce the number of generated refinements, MoFa sorts all nodes and edges of a fragment in the order in which they were added. Nonetheless, many duplicates are generated, with time-consuming isomorphism tests as a consequence. Two extensions exist for MoFa; the first treats rings as single units and the other treats chains of arbitrary length as a single unit. One of the advantages of treating rings as single units becomes clear when fragmenting steroid structures. Normally, MoFa considers more than 300,000 fragments per steroid, whereas the ring extension generates only 93 fragments. Another advantage is that the ambiguity of aromatic bond representations in rings, either single or double, is circumvented. To generate unique representations, the algorithm dictates a strict, depth-first traversal of the subgraph lattice, hence the name ‘depth-first search’ code (dfs-code). Since the string of concatenated edge/vector representations resembles the sequence of letters in a word, graph representations are compared in the same way, that is, lexicographically. The elements of the string are sequentially compared until a mismatch is found or if one string ends. Lower edge/vector labels precede higher ones; if all labels match, the shorter string precedes the longer. The dfs-code of a fragment determines which nodes can be extended, thereby restricting the number of refinements for that fragment. Appearance lists are used instead of embeddings; hence, subgraph isomorphism tests are still necessary for the graphs in these appearance lists. By concatenating all entries of the matrix, a string is formed that is used for lexicographic ordering of the graphs. In this way, embeddings are rapidly created for new fragments made from joining or extension. As stated before, finding subgraph isomorphisms is a laborious task compared to other search problems, and therefore time consuming. Gaston stores all embeddings, in 34 Computational Approaches order to restrict generation of fragment refinements to those that actually appear in the database, and for isomorphism testing. Comparison of four frequent substructure-mining algorithms in terms of a performance. The runtime per fragment found is also provided to correct for the runtime overhead due to the higher number of fragments at lower support values. Benchmarks were carried out on a comprehensive set of graph databases, including molecular databases. For example, a support value of 4% resulted in 37,727 fragments of which the largest had 22 bonds. For this, molecules were 35 Chapter 2 randomly divided into sets of various sizes. Sample measurements are provided for illustrating the quantitative comparison of the algorithms. Size and contents of the database, the minimum support value, as well as implementation details and even the underlying hardware architecture may influence performance of the algorithm. The data in Table 1 are indicative for the overall outcome of the quantitative comparison. For all algorithms, lower support values resulted in an exponential rise in runtime. This is probably due to the runtime overhead caused by the exponential rise in found fragments at lower support values. MoFa, which stores only one subgraph embedding per node in the search tree, was also memory efficient. Gaston needed most memory, since with this method embedding lists for new fragments are based on those of ‘parent’ fragments. Embedding lists are not used in gSpan, which, in fact, speed up testing, especially for larger fragments. Some memory architectures penalize the memory-intensive 36 Computational Approaches operations of Gaston. Although MoFa was the slowest in all tests, it offers more functionality for molecular databases, e. This can be useful for the exploration of biochemical 16 reactions where this length is less important. Interestingly, the four fragment miners mentioned above have been made available as 17 a single package named ParMol (Parallel Molecular Mining). Other algorithms for frequent fragment mining that are more database-centric include 18 19 18 Molfea and Warmr. Molecules are encoded as basic facts, and queries result in a combination of facts.