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In case of further absences discount naproxen 500 mg with mastercard, the practicals should be made up for by attending the practicals with another group in the same week cheap naproxen 500mg without prescription, or a medical certificate needs to be presented cheap naproxen 500 mg line. Please note that strictly only a maximum of 3 students are allowed to join another group to make up for an absence. Requirements for signing the Lecture book: The Department may refuse to sign the Lecture book if the student is absent from practicals more than allowed in a semester. Assessment: The whole year 5 written examinations are held, based on the material taught in the lectures and practicals. At the end of the first semester the written examinations are summarized and assessed by a five grade evaluation. If the student failed - based on the results of written exams - he must sit for an oral examination during the examination period. The final exam at the end of the second semester consists of two parts: a written minimum entry test and an oral exam (1 theoretical, 1 practical topic and 1 practical picture). The practical pictures will be demonstrated on the last lectures of the 2nd semester. Those who fail the minimum entry test, are not allowed to take the oral exam and they have to repeat the minimum entry test part as well. Those who fail the oral exam only, do not have to take the written test on the B or C chance. Requirements for examinations: The examination (written and oral) is based on the whole lecture and practical material (Practicals in Laboratory Medicine, eds. Year, Semester: 3rd year/1st semester Number of teaching hours: Lecture: 30 Practical: 30 1st week: to antibiotics Lecture: 1. Active and passive immunization Practical: Rules of collecting clinical specimens 12. Antimicrobial drugs for systemic Practical: Overview of human pathogenic administration bacteria 8. Vibrio, Campylobacter, Helicobacter 5th week: Practical: Wound, skin and soft tissue infections Lecture: 9. Pseudomonas and other non- 13th week: fermentative Gram negative bacilli Lecture: 25. Rickettsiae Practical: Bacterial respiratory tract diseases Practical: Urinary tract infections. Mycology I infections and food poisoning Practical: Central nervous system diseases caused by bacteria 12th week: Lecture: 23. Missed practice may be made up in the practice with another group only in the same week. A list of questions and the examination rules will be announced in the Department at the beginning of the 2nd semester. Year, Semester: 3rd year/1st semester Number of teaching hours: Lecture: 30 Practical: 45 1st week: Practical: Introduction Lecture: -Introduction to anatomical pathology. Foreign body granuloma 3rd week: 8th week: Lecture: - Abnormal glycogen and protein Lecture: - Diagnostic immunohistochemistry. Bile stasis in the liver due to extrahepatic bile duct 10th week: obstruction Lecture: - Opportunistic infections. Systemic effects of neoplasia (cachexia, 5th week: immunosupression, paraneoplastic syndromes). Myelofibrosis Practical: Repeating practice 14th week: Lecture: - Malignant lymphomas. Requirements Validation of Semester in Pathology: Missing two practicals (histopathology and gross pathology together) is tolerable. Intracurricular replacement of histopathological and/or gross pathological classes is possible on the same week. In case of failure student can repeat these parts of the exam during the exam period. An acceptable result in the practical exam is mandatory to apply for the oral part. During the theoretical exam 3 titles are to be worked out and presented orally and one photo about a slide (with different magnifications) has to be described and diagnosed also orally. During the theoretical exam 3 titles are to be worked out (one from the material of the 1st semester, and two from the material of the 2nd semester). One photo about a slide (with different magnifications) has to be described and diagnosed (from the whole year). At least a (2) level of gross pathological examination and recognition of the histopathological alteration achieved in the course of a previous unsuccessful examination is acceptable without repeating for the next (B or C chance) examination. Cancer registries 6th week: Lecture: Role of viruses in the malignant 13th week: transformation. Lecture: Prevention strategies in cancer 7th week: Lecture: Chemical carcinogenesis. Carcinogenic Requirements Conditions of signing the Lecture book at the end of the semester. Although attendance at lectures is not compulsory, it is highly recommended, since the material covered in the lectures will be examined.

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The history and physical examination is the most important test in dif- ferentiating between the two disorders buy 250 mg naproxen amex. The history and physical examination while often unhelpful is better than imaging tests in differentiating between the two disorders naproxen 250mg low price. The history and physical examination is typically unhelpful in differenti- ating between the two disorders buy 500 mg naproxen amex. Imaging tests are rarely helpful, may exacerbate the condition and worsen the prognosis. This patient presents with signs and symptoms of high-grade small-bowel obstruction. Statistically speaking, a hernia would be the most likely cause of small- bowel obstruction in a patient without previous abdominal operations or other causes of adhesions. History and physical examination is often inadequate in differentiating mechanical large-bowel obstruction from functional large-bowel obstruction, and this would be especially true in a patient with Alzheimer disease and pos- sible cause for functional large-bowel obstruction. Localized tenderness in a patient with small-bowel obstruction may indicate an isolated segment of closed-loop obstruction, localized ischemic injury, or localized perforation. Because the symptoms and physical findings associated with large-bowel obstruction are nonspecific, they can be easily overlooked by both the patient and the physician. Adhesions represent the most common cause of small-bowel obstruction, whereas colorectal carcinoma is the most common cause of large-bowel obstruction. Five days ago she returned from a camping trip in New Mexico, but did not drink from natural streams. Rectal examination demonstrates no tenderness or masses, and is Hemoccult negative. Five days ago, she was on a camping trip in New Mexico but did not drink from natural streams. The abdominal exami- nation reveals hyperactive bowel sounds, no masses, and diffuse mild tenderness without peritoneal signs. Know a diagnostic approach to acute diarrhea including the role of fecal leuko- cytes and assessment for occult blood in the stools. Understand that volume replacement and correction of electrolyte abnormalities are the first priorities in treatment of diarrhea. Be familiar with a rational workup for acute diarrhea, and know the common etiologies of diarrhea, including Escherichia coli, Shigella, Salmonella, Giardia, and amebiasis. Her most imme- diate problem is volume depletion as evidenced by her dry mucous membranes, tachycardia, and hypotension. The first priority should be for acute replacement of intravascular volume, usually with intravenous normal saline. The electrolytes should be assessed, and abnormalities, such as hypokalemia, should be corrected. After volume repletion, the next priority is to determine the etiology of the diarrhea. This patient does not have a history consistent with inflammatory bowel disease or prior abdominal surgeries. She had been camping in New Mexico recently, which predisposes her to several pathogens: E coli, Campylobacter, Shigella, Salmonella, and Giardia. Fetal leukocyte is an inexpensive and good test to differentiate between the various types of infectious diarrhea. In general, ova and parasite evaluation is unhelpful unless the history strongly points toward a parasitic source, or the diarrhea is prolonged. Because of the severity of this patient’s symptoms, empiric antibiotic therapy such as with cipro- floxacin might be indicated. For instance, travelers to Mexico or Asia will frequently contract enterotoxigenic E coli as a causative agent. Those travel- ing to Russia and campers and backpackers will often be affected by Giardia. Salmonella or Shigella can be found in undercooked chicken, enterohemorrhagic E coli in undercooked ham- burger, and Staphylococcus aureus or Salmonella in mayonnaise. For example, illness within 6 hours of eating a salad (mayonnaise) suggests S aureus, 8-12 hours post-ingestion suggests Clostridium perfringens, and 12 to 14 hours post-ingestion suggests E coli (see Table 21–1). Day-care settings are particularly common locales for Shigella, Giardia, and rotavirus transmission. Patients in nursing homes and who were recently in the hospital may develop C difficile colitis from antibiotic use. In addition, immune- compromised patients with prior history of C difficile infections may remain colonized and recurrent clinical infections despite appropriate treatment. Clin ical Presentation Most patients with acute diarrhea have self-limited processes, and do not require much workup. Exceptions to this rule include profuse diarrhea, dehydration, fever exceeding 38. Mortalities related to diarrheal illnesses are generally due to the inade- quate recognition and treatment of dehydration, electrolyte disturbances, and acidosis.

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Most skin lightening lotions that use kojic acid as one of their ingredients also use small amounts of hydroquinone as well as glycolic acid (Fig discount naproxen 500mg without prescription. In addition purchase naproxen 250 mg with visa, kojic acid is found to prevent photodamage and subsequent wrinkling of the skin in the hairless mouse best naproxen 250 mg. It is a good chelator of transition metal ions and a good scavenger of free radicals therefore it is an effective agent for photoprotection (Mitani, 2001). Current evidence suggests that it induces skin depigmentation through suppression of free tyrosinase, mainly due to chelation of its copper at the active site of the enzyme (Chen, 1991; Jun, 2007; Lee, 2006). It has been demonstrated to be responsible for therapy and prevention of pigmentation, both in vitro and in vivo and being used for topical application. In treatment of melasma which continues to be a difficult problem, the addition of kojic acid in a gel containing glycolic acid and hydroquinone improved melasma. Previous antimicrobial activity studies showed that kojic acid was more active against gram negative bacteria than against gram positive ones (Bentley, 2006). However, some of its derivatives have shown adverse effects different from kojic acid’s antibacterial activity results (Aytemir, 2003a, 2003b; Fassihi, 2008; Kotani, 1978; Masoud, 1989; Petrola, 1985; Veverka, 1992). According to its antibacterial and fungicidal properties, kojic acid is used as a food additive (Burdock, 2001). There are several forms of kojic acid containing products including soap, cream, lotion and gel. Kojic acid also has antifungal and antibacterial properties in it, making it a perfect ingredient to be used in soap. Women who choose a kojic acid lotion tend to use it to treat smaller areas of the skin that have been affected by hyperpigmentation, age spots or hormone related skin conditions brought on by pregnancy or birth control pills. Some women favor this lotion because it absorbs directly into the skin much better than creams or soaps. One of the greatest benefits to using kojic acid is reduction of getting wrinkles when you use the lotion before exposure to the sun. Based on such tyrosinase-inhibiting activity of kojic acid, there have been proposed a lot of cosmetic compositions containing kojic acid as an active ingredient. There are a variety of kojic acid creams available for purchase online and in certain specialty stores. Each one has its own unique blend of ingredients which set 8 Medicinal Chemistry and Drug Design them apart from one another. Some creams combine various vitamins like A and E which give them different effects. The reason many people mix these vitamins within the kojic acid creams is to help them alleviate the skin irritation that has been said to occur with kojic acid products. These ingredients are added to this base to help counteract the sensitivity that is associated with prolonged use of kojic acid when it is used by itself. The development of tyrosinase inhibitors is of great concern in the medical, agricultural, and cosmetic fields. Among the many kinds of tyrosinase inhibitors, kojic acid has been intensively studied. It acts as a good chelator of transition metal ions such as Cu2+ and Fe3+ and a scavenger of free radicals. This fungal metabolite is currently applied as a cosmetic skin-lightening agent and food additive to prevent enzymatic browning. Kojic acid shows a competitive inhibitory effect on the monophenolase activity and a mixed inhibitory effect on the diphenolase activity of mushroom tyrosinase. However, its use in cosmetics has been limited, because of the skin irritation caused by its cytotoxicity and its instability during storage. Accordingly, many semi-synthetic kojic acid derivatives have been synthesized to improve its properties by converting the alcoholic hydroxyl group into an ester, hydroxyphenyl ether, glycoside, amino acid derivatives, or tripeptide derivatives (Kang, 2009; Lee, 2006). It was also confirmed that the kojic acid-phenylalanine amides reduced the amount of dopachrome production during the melanin formation. The metal complexes of kojic acid-phenylalanine-amide exhibited potent tyrosinase inhibitory activity both in vitro enzyme test and in cell-based assay system. These results demonstrated that metal complex formation could be applied as a delivery system for hydrophilic molecules which have low cell permeability into cells. In addition, these new Kojic Acid Derivatives 9 materials can be used as an effective whitening agent in the cosmetic industry or applied on irregular hyperpigmentation (Kwak, 2010). Furthermore, kojic acid was shown to inhibit different enzymes relevant to the undesirable melanosis of agricultural products, which is related to its coordination ability to, e. Chemical structure of some synthetic kojic acid derivatives as tyrosinase inhibitors. It was reported that compound, joining to two pyrone rings of kojic acid through an ethylene linkage, exhibited 8 times more potent mushroom tyrosinase inhibitory activity than that of kojic acid and also showed superior melanin synthesis inhibitory activity using B16F10 melanoma cell (Lee, 2006). A series of kojic acid derivatives containing thioether, sulfoxide and sulfone linkages were synthesized. Sulfoxide and sulfone derivatives decreased and kojyl thioether derivatives containing appropriate lipophilic various alkyl chains increased tyrosinase inhibitory activity (Rho, 2010).

Product liability: the publishers cannot guarantee the accuracy of any information about dosage and application contained in this book 500mg naproxen free shipping. In every individual case the user must check such information by consulting the relevant literature generic 250mg naproxen with mastercard. About 200 250 mg naproxen,000 natural products of plant origin are known and many more are being identifed from higher plants and microorganisms. Some plant-based drugs have been used for centuries and there is no alternative medicine for many drugs, such as cardiac glycosides. Therefore, medici- nal plants and their bioactive molecules are always in demand and are a central point of research. While planning this book, we endeavored to incorporate ar- ticles that cover the entire gamut of current medicinal plants research. The aim of this book was to review the current status of bioactive molecules and medicinal plants research in light of the surge in the demand for herbal medicine. We hope that this book will be useful for researchers in academia, industry, and agriculture planning. Finally, we would like to acknowledge our contributors, who have made seri- ous efforts to ensure the high scientifc quality of this book. Sukhadia University as an Associate Professor in 1991 and became a Professor in 2001. He did his postdoctoral study at the University of Tours, France (1983–85) and subsequently worked as visiting professor at the University of Tours (1991) and University of Bor- deaux 2, France (1995, 1999, 2003, 2006). He has published more than 100 research papers and review articles in reputed journals and books. He joined the Uni- versity of Tours as a faculty member in 1982, became associate professor in 1987, and a full Professor in 1993 at the faculty of Pharmacy, University of Bor- deaux 2, Bordeaux, France. He is currently group leader of a “study group on biologically active plant substances” at the Institute of Vine and Wine Sciences, which comprises 20 scientists and research students. He has published more than 80 research papers in internationally recognized journals. He is involved in developing courses and research on phytochemistry and biological properties of compounds from vine and wine in France and has traveled widely as a senior professor. Scientists from several countries are working in his laboratory and his research is supported by funds from the Vinegrowers Association, Ministry of Higher Education and Research, and various private enterprises. Sukhadia University Laboratory of Biomolecular Udaipur-313001 Technology, Department of Botany India M. Brisson 37007-Salamanca Department of Biochemistry Spain and Microbiology, Research in Heath corchpu@usal. Ganeshaiah Quebec Department of Genetics and Plant Canada Breeding G1K 7P4 University of Agricultural Sciences louise. Geszprych Department of Forest Biology Department of Vegetable College of Forestry and Medicinal Plants Sirsi 581401 Warsaw Agricultural University India Nowoursynowska 159 02-776 Warsaw Sumita Jha Poland Centre of Advanced Study in Cell and Chromosome Research Seemanti Ghosh Department of Botany Centre of Advanced Study in University of Calcutta Cell and Chromosome Research 35 Ballygunge Circular Road Department of Botany Calcutta 700019 University of Calcutta India 35 Ballygunge Circular Road sjbot@caluniv. Mathur Laboratory of Plant Physiology Laboratory of Biomolecular Faculty of Agricultural Technology, Department of Botany Biotechnology M. Sukhadia University Agricultural University of Athens Udaipur-313001 Iera Odos 75 India 11855 Athens Greece Professor Jean-Michel Mérillon spiroskintzios@usa. Salim Laboratory of Biomolecular College of Pharmacy Technology, Department of Botany The Ohio State University M. Węglarz Ashoka Trust for Research in Department of Vegetable Ecology and the Environment #659 and Medicinal Plants 5th A Main Warsaw Agricultural University Hebbal Nowoursynowska 159 Bangalore 560024 02-776 Warsaw India Poland weglarz@alpha. Plant secondary metabolites can also serve as drug precursors, drug prototypes, and pharmacological probes. Re- cent developments in drug discovery from plants, including information on approved drugs and compounds now in clinical trials, are presented. There are also several plant extracts or “phytomedicines” in clinical trials for the treat- ment of various diseases. Keywords Natural products, Plant-derived drugs, Drug discovery, Drug development, Drug precursors, Drug prototypes, Pharmacological probes, New therapeutic agents, Clinical trials, Accelerated discovery techniques 1. Plants have also been utilized for additional purposes, namely as arrow and dart poisons for hunting, poisons for murder, hallucinogens used for ritualistic purposes, stimulants for endur- ance, and hunger suppression, as well as inebriants and medicines. The plant chemicals used for these latter purposes are largely the secondary metabolites, which are derived biosynthetically from plant primary metabolites (e. These secondary metabolites can be classifed into several groups according to their chemical classes, such alkaloids, terpenoids, and phenolics [1]. Kinghorn Arrow and dart poisons have been used by indigenous people in certain parts of the world with the principal ingredients derived from the genera Aco- nitum (Ranunculaceae), Akocanthera (Apocynaceae), Antiaris (Moraceae), Chondrodendron (Menispermaceae), Strophanthus (Apocynaceae), and Strych- nos (Loganiaceae) [2]. Most compounds responsible for the potency of arrow and dart poisons belong to three plant chemical groups, namely the alkaloids (e.

This is a medical emergency and if the colonic dilation does not resolve within 24 hours an emergency colectomy is indicated generic naproxen 500 mg with amex, as the risk of perforation is high safe 250mg naproxen. This is a transmural inflammatory condition affecting mainly the distal ileum or colon purchase naproxen 250 mg visa, but may affect the entire gastro-intestinal tract. After terminal ileal resections, to reduce diarrhoea due to bile salt malabsorption: • Cholestyramine, oral, 2–8 g daily. Emergency management at specialist facility will include: » resuscitation with parenteral fluids; » blood transfusions; » corticosteroids; » antibiotics; and » nasogastric suction as indicated. Peri-anal disease There is evidence of recurrence on withdrawal of therapy and prolonged treatment may be indicated. There is a decreased frequency of bowel action and patients should be assessed individually. Constipation may have many causes: » incorrect diet (fibre and fluid); » certain drugs; » lack of exercise; » metabolic; » pregnancy; » endocrine; » old age; » neurogenic; » psychogenic disorders; » lower bowel abnormalities; » chronic use of enemas and » ignoring the urge; laxatives; » cancer of the bowel; » behavioural problems in children. Stimulant laxatives For short term use only, except in the elderly where long-term treatment may be indicated: • Sennosides A and B, oral, 7. Polyethylene glycol-based purges For acute bowel preparation or for chronic constipation on specialist advice. Complications that may develop in severe disease are strictures, ulceration, Barrett’s oesophagus and adenocarcinoma of the oesophagus. Recurrence of symptoms After endoscopic confirmation of disease: • Omeprazole, oral, 20 mg daily. There is no convincing evidence that long-term treatment of Barrett’s oesophagitis reduces dysplasia or progression to malignancy. Antimicrobial therapy The administration of prophylcatic antibiotics to patients with severe necrotising pancreatitis prior to the diagnosis of infection is not recommended. In most patients this is a chronic progressive disease leading to exocrine and endocrine insufficiency. Small frequent meals, and restricted fat intake – reduces pancreatic secretion and pain. When weight loss is not responding to exogenous enzymes and diet, consider supplementation with medium chain triglycerides. This should be considered in patients who develop worsening pain, new onset diabetes or deterioration in exocrine function. Malabsorption Start treatment when >7 g (or 21 mmol) fat in faeces/24 hours while on a 100 g fat/day diet. Auto-immune hepatitis Patients with hepatitis persisting with negative viral markers and no hepatotoxins. Thereafter, to attain 2–3 soft stools a day: • Lactulose, oral, 10–30 mL 8 hourly. Exclude infection, high protein load, occult bleed, sedatives and electrolyte disturbances. Large-volume ascites Large volume paracentesis is the method of choice as it is faster, more effective and has fewer adverse effects compared to diuretics. Oesophageal varices To reduce the risk of bleeding: • Propranolol, oral 10–20 mg 12 hourly. Hepatitis A and E only cause acute hepatitis, whilst B and C cause acute and chronic hepatitis. All exposure incidents must be adequately documented for possible subsequent compensation. This should preferably be done percutaneously by inserting a catheter under ultrasound guidance. Duration of antibiotic therapy is ill-defined, but may need to be for as long as 12 weeks in cases of multiple abscesses. Ultrasound resolution is very slow and is not useful for monitoring response to therapy. It is essential to exclude pyogenic infection (a diagnostic aspirate should be taken under ultrasound guidance in all cases where there is doubt). If diarrhoea does not settle on antibiotic withdrawal or if pseudomembranous colitis is present: • Vancomycin, oral, 125 mg 6 hourly. In this setting polymicrobial infection with anaerobes and Enterobacteriaceae are usually found. Primary or spontaneous bacterial peritonitis is much less common and usually complicates ascites in patients with portal hypertension. This is not usually polymicrobial but due generally to Enterobacteriaceae such as E. Spontaneous bacterial peritonitis is often culture-negative but is 9 3 diagnosed by ascitic neutrophil count >0.

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Prognosis r Modifiable: Obesity naproxen 500 mg line, alcohol intake discount 250 mg naproxen fast delivery, diet (especially Despite advances in treatment buy cheap naproxen 250 mg, overall mortality is still high salt intake). Complications Hypertension is a major risk factor for cerebrovascular Pathophysiology disease (strokes), heart disease (coronary artery disease, r Hypertension accelerates the age-related process of left ventricular hypertrophy and heart failure) (see Table arteriosclerosis ‘hardening of the arteries’ and predis- 2. Arterioscler- include peripheral vascular disease and dissecting aortic osis, through smooth muscle hypertrophy and intimal aneurysms. In r The chronic increased pressure load on the heart re- severehypertension,retinalhaemorrhages,exudatesand sults in left ventricular hypertrophy and over time this papilloedema are features of malignant hypertension. Saltand r Benign hypertension and small arteries: There is hy- water retention occurs, which can itself worsen hyper- pertrophy of the muscular media, thickening of the tension. In cases of doubt, r Routine investigations must include fasting plasma 24-hour blood pressure recordings may be helpful such glucose, serum total cholesterol and lipid profile, as when ‘white coat’ hypertension is suspected. Management Peripheral arterial disease Treatment is based on the total level of cardiovascular Definition risk and the level of systolic and diastolic blood pressure Peripheralarterialdiseasedescribesaspectrumofpatho- (see Tables 2. Stopping smoking as well as the ac- tions mentioned above will also reduce overall cardio- Age vascular risk. If after 3 months their M > F systolic blood pressure is above 139 or the diastolic above 89, treatment should be started. The remainder Geography of patients and those with low or average risk should More common in the Western world. Atheromatous plaques form especially in larger vessels at areas of haemodynamic stress such as at the bifurcation Prognosis of vessels and origins of branches. It may affect younger Patients with untreated malignant hypertension have a patients, particularly diabetics and smokers. In general the risks from Arteriosclerosis, ‘hardening of the arteries’, is an age- hypertension are dependent on: related condition accelerated by hypertension. Arterial Venous This can lead to ‘unfolding of the aorta’ and aortic Position Tips of toes and Gaiter area regurgitation. With increasing severity of ischaemia the Hypertension may be the underlying cause or may be claudication distance falls. Eventually the patient develops pain at rest arterial tree, therefore associated symptoms and signs and this indicates critical arterial insufficiency and is a should be elicited, e. On examination, signs include cool, dry skin with loss of hair, thready or absent pulses in the affected areas Complications and a lack of venous filling. Prognosis Management r Five-year patency rates with femoro-distal bypass vary Risk factors should be modified where possible, stop- between 30 and 50%, aortoiliac reconstruction has a pa- ping smoking in particular may prevent further dete- tency rate of 80%. Care peri-operatively and during long-term follow-up is is- should be taken to avoid trauma. Arterioscle- An aneurysm is defined as an abnormal focal dilation of rosis in older patients is difficult to treat surgically, as an artery (see Table 2. A true aneurysm may be further subdivided stenoses or occlusions in medium-sized arteries into saccular in which there is a focal out-pouching suchastheiliac,femoralandrenalarteries;however, or fusiform where there is dilation of the whole cir- as patients often present late the disease may be too cumference of the vessel. A guide wire is inserted and then a bal- occurs following penetrating trauma when there is a loon fed over the wire and inflated within the lesion. They may dissect and cut off blood critical ischaemia or severely limiting intermittent supply to tissue or rupture with resulting haemor- claudication, because failed grafting worsens symp- rhage. In addi- r Altered flow patterns predispose to thrombus forma- tion, most patients have other conditions such as tion, which may embolise to distal arteries or cause ischaemic heart disease, diabetes and cerebrovascu- occlusion at the site of the aneurysm. Abdominal aortic aneurysms may be found incidentally as a central expansile mass on examination or as calcifi- Sex cation on an X-ray. Patients may present with a dull, aching chronic or intermittent epigastric or back pain due to expansion. Geography Rupture causes a tearing epigastric pain that radiates Becoming more common in the developed world. Occasionally a small leak ‘herald bleed’ Riskfactorsareasforatherosclerosis,includingsmoking, maycauseashorter,lesssevereepisodeofpainsomedays hypercholesterolaemia, age, sex, diabetes. More than half of aneurysms over 6 cm will rupture Pathophysiology within 2 years – thromboembolism. The arterial wall becomes thinned and is replaced with fibrous tissue and stretches to form a dilated saccular or Investigations fusiform aneurysm. Suprarenal aneurysms have a much poorer prognosis with a high risk of renal impairment. Many patients have Management concomitant ischaemic heart disease or cerebrovascular r Ruptured abdominal aortic aneurysm is a surgical disease, which affects outcome. O negative blood may be required untilbloodiscross-matched,asbloodlosscanbemas- Definition sive. Aortic dissection is defined as splitting through the en- r Surgery at a specialist centre gives the best outcome, dothelium and intima allowing the passage of blood into but patients may not be fit for transfer. If the aneurysm is too Aetiology low, or when the iliac and femoral arteries are ei- Predisposingfactorstothoracicaorticaneurysms,which ther aneurysmal or too diseased with atherosclerosis, may dissect include hypertension, atherosclerosis, bicus- a‘trouser’ bifurcation graft is used to anastomose to pid aortic valve, pregnancy, increasing age and Marfan’s the iliac or femoral arteries.

The potential use as an integrated strategy aimed at prioritizing and identifying drug targets of neglected-disease pathogens will be put forward trusted 250mg naproxen, and the argument for future research involving the application of many tools and strategies will be discussed generic 250mg naproxen free shipping. Systems and network biology: Basic concepts Systems biology is a holistic approach that involves the study of the inter-relationships of all the different elements in a biological system in order to understand non-deterministic behaviors that emerge from interaction between the cellular components and their environment and not by studying them in an isolated manner purchase naproxen 250 mg, one at a time (Hood and Perlmutter 2004, Weston and Hood 2004, Kohl and Noble 2009). These interactions are also responsible for performing processes critical to cellular survival. For example, during transcription process the regulatory proteins can activate or inhibit the expression of genes or regulate each other as part of gene regulatory networks. Likewise, the cellular metabolism can be integrated into a metabolic network whose fluxes are regulated by enzymes. The biological systems consisting of interacting cellular components have led to the use of graph theory and mathematical tools based on graphs where the individual components are represented by nodes and the interactions by links (Fig. Albert and Barabási (2002) have shown the general properties found among several networks ranging from the Internet to social and biological networks (Albert and Barabási 2002). The analysis of topology of those networks showed that they deviate substantially from randomly built networks as studied by Erdös and Rényi (Fig. Also, these networks did not show a well-shaped frequency distribution of the number of links per node as expected from randomly formed networks; instead, they showed a power-law distribution, which is characteristic of scale-free networks (Fig. In scale-free network, the majority of nodes have only a few links, whereas very few nodes have a large number of links. Those nodes are called hubs and they represent the most vulnerable points of a network (Barabasi and Albert 1999, Albert et al. The topological features of networks can be quantified by measuring topological parameters whose information content provides a description from local (e. For example, the nodes of a graph can be characterized by means of the number of links they have (the number of other nodes to which they are connected). In directed networks, it is possible to distinguish the number of directed links that points toward the node (in-degree), and the number of directed edges that points outward the node (out-degree). The node degree characterizes individual nodes; however, in order to relate this parameter to whole network, a network degree distribution can be defined. The degree distribution P(k) represents the 30 Medicinal Chemistry and Drug Design fraction of nodes that have degree k and it is obtained by counting the number of nodes N(k) that have k = 1, 2… links and dividing it by the total number of nodes N. The degree distributions of numerous networks such as the Internet, social, and biological networks, follow a power law (Fig. This function is intimately linked to the growth of the network in which new nodes are preferentially attached to already established nodes, a property that is also thought to characterize the evolution of biological systems (Jeong et al. Three types of network models and their associated distributions: (a) random network, (b) scale-free network, and (c) hierarchical network. Analysis of Protein Interaction Networks to Prioritize Drug Targets of Neglected-Disease Pathogens 31 The distance between any two nodes in a network could be defined by the path length. Nevertheless, it could have many alternative paths between two nodes in a network. The path with the smallest number of links between the selected nodes (shortest path) is of special interest. A common characteristic of several biological networks, including metabolic networks (Jeong et al. The main biological implications of this characteristic are related to: i) how the biological networks are capable of rapid responses to perturbations; ii) its capacity to employ alternative roads for the same input and output; and iii) the ability to efficiently compensate the perturbations in essential pathways. Another important issue derived from network analysis is the concept of modularity, which can be used to describe how a group of physically or functionally linked nodes work together to achieve a particular function. The topological parameter used to quantify the modularity in a network is the clustering coefficient Ci, which represents the ratio between the number of links connecting nodes adjacent to node i and the total possible number of links among them (Watts and Strogatz 1998). It is worth noting that in first instance, the modularity concept might be in contradiction of the scale-free nature of the networks because the presence of modules implies that there are clusters of nodes that are relatively isolated from the rest of the network. However, it has been demonstrated that modularity and scale-free properties naturally co-occur in biological networks indicating that modules are not independent, instead, they are combined to form a hierarchical network (Fig. The most common representation of a module or cluster in a network is as a highly interconnected group of nodes. In addition to the modules, within a network, small and recurring sub-graphs, known as interaction motifs, with well-defined topologies can be identified (Fig. The frequency analysis of these interaction motifs in networks revealed that they are over-represented when compared to a randomized version of the same network, suggesting that not all sub- graphs are equally significant in networks and that interaction motifs form functionally separable building blocks of cellular networks (Mangan and Alon 2003, Wuchty et al. For example, triangle motifs, also called feed-forward loops in directed networks, appear in both transcription-regulatory and neural networks. Likewise, there is evidence suggesting that specific motif type aggregates to form large motif clusters and that also appear to be commonly involved with certain functional roles (Milo et al. The relevance of any node in mediating the communications flow among other nodes in the network is quantified by its betweenness centrality, which is defined as the total number of non-redundant shortest paths going through a certain node or edge (Freeman 1977). Girvan and Newman (2002), have proposed that the edges with high betweenness are the ones that are “between” network clusters; therefore, the information flow within a network could be altered by removing these edges (Girvan and Newman 2002).

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