Developed and produced for http://www.MechanismsInHematology.com by Mechanisms in Medicine Inc. Animation description: The Antiglobulin Tests (also known as Coombs test). The direct antiglobulin test (DAT) is requested when immune-mediated hemolytic anemia is suspected. A blood sample must be drawn. The patient's red blood cells may have antibodies (and other complement system factors) on the surface of some of the red blood cells (abbreviated as RBCs in this animation). The blood sample is washed to remove the patient's plasma while leaving the red blood cells intact with their attached antibodies. These red blood cells are incubated with anti-human globulin containing both anti-IgG and anti-complement. The anti-human globulin binds to the patient's antibody, coating the red blood cells, resulting in agglutination. A positive DAT indicates that the red cells have been coated in vivo with immunoglobulin or complement and may suggest the presence of an immune-mediated hemolytic process. The DAT is used in the investigation of transfusion reactions, auto-immune hemolytic anemia, hemolytic disease of the newborn and drug-induced hemolysis. Rarely the DAT may be positive in a normal individual. To detect whether human anti-red blood cell antibodies are present in the plasma of a patient, an indirect antiglobulin test (IAT) is used. Unlike the DAT which relies on the red blood cells in the sample, the IAT only deals with the extracted plasma. Unbound human anti-red blood cell antibodies remain in the plasma. The plasma is then incubated with reagent red blood cells selected to detect specific antibodies that are considered clinically significant. The anti-red blood cell antibodies of the patient's plasma bind to reagent red blood cells to form antigen-antibody complexes. The addition of anti-human globulin to these complexes results in agglutination of the red blood cells. A positive IAT indicates the presence of a red cell antibody in the patient.
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This animation focuses on the renin angiotensin aldosterone system (RAAS), a classic endocrine system that helps to regulate long-term blood pressure and extracellular volume in the body. Many aspects of cardiovascular disease progression can be directly linked to the RAAS system. Mechanisms such as vascular inflammation, generation of reactive oxygen species and alterations of endothelial function are all known to play a role in atherosclerosis.
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Developed and produced by http://www.MechanismsinMedicine.com Animation Description: This animation starts with the explanation of bacterial cell wall synthesis, the process targeted by ß-Lactams. Structurally, most bacteria consist of a cell membrane surrounded by a cell wall and, for some bacteria, an additional outer layer. Internal to the cell membrane is the cytoplasm which contains ribosomes, a nuclear region and in some cases granules and/or vesicles. Depending on the bacterial species, a number of different external structures may be found such as a capsule, flagella and pili. In gram negative bacteria, the gap between the cell membrane and the cell wall is known as the periplasmic space. Most gram positive bacteria do not possess a periplasmic space but have only periplasm where metabolic digestion occurs and new cell peptidoglycan is attached. Peptidoglycan, the most important component of the cell wall, is a polymer made of N-acetyl muramic acid alternating with N-acetyl glucosamine which are cross-linked by chains of four amino acids. The function of the bacterial cell wall is to maintain the characteristic shape of the organism and to prevent the bacterium from bursting when fluid flows into the organism by osmosis. Synthesis of peptidoglycan and ultimately the bacterial cell wall occurs in a number of stages. One of the first stages is the addition of 5 amino acids to N-acetyl muramic acid. Next, N-acetyl glucosamine is added to the N-acetyl muramic acid to form a precursor of peptidoglycan. This peptidoglycan precursor is then transported across the cell membrane to a cell wall acceptor in the periplasm. Once in the periplasm, the peptidoglycan precursors bind to cell wall acceptors, and undergo extensive crosslinking. Two major enzymes are involved in crosslinking: transpeptidase and D-alanyl carboxypeptidase. These enzymes are also known as penicillin binding proteins because of their ability to bind penicillins and cephalosporins. Eventually, several layers of peptidoglycan are formed all of which are crosslinked to create the cell wall. Gram positive bacteria have many more layers than gram negative bacteria and thus have a much thicker cell wall. Beta-lactam antibiotics include all penicillins and cephalosporins that contain a chemical structure called a beta-lactam ring. This structure is capable of binding to the enzymes that cross-link peptidoglycans. Beta-lactams interfere with cross-linking by binding to transpeptidase and D-alanyl carboxypeptidase enzymes, thus preventing bacterial cell wall synthesis. By inhibiting cell wall synthesis, the bacterial cell is damaged. Gram positive bacteria have a high internal osmotic pressure. Without a normal, rigid cell wall, these cells burst when subjected to the low osmotic pressure of their surrounding environment. As well, the antibiotic-penicillin binding protein complex stimulates the release of autolysins that are capable of digesting the existing cell wall. Beta-lactam antibiotics are therefore considered bactericidal agents. Bacterial resistance to beta-lactam antibiotics may be acquired by several routes. One of the most important mechanisms is through a process known as transformation. During transformation, chromosomal genes are transferred from one bacterium to another. When a bacterium containing a resistance gene dies, naked DNA is released into the surrounding environment. If a bacterium of sufficient similarity to the dead one is in the vicinity, it will be able to uptake the naked DNA containing the resistance gene. Once inside the bacterium, the resistance gene may be transferred from the naked DNA to the chromosome of the host bacteria by a process known as homologous transformation. Over time, the bacterium may acquire enough of these resistance genes to result in a remodelling of the segment of the host DNA. If this remodelled DNA segment codes for cross-linking enzymes (i.e. penicillin binding proteins), the result is the production of altered penicillin binding proteins. These altered penicillin binding proteins can still cross-link the peptidoglycan layers of the cell wall but have a reduced affinity for beta-lactam antibiotics thus rendering the bacterium resistant to the effects of penicillin and other beta-lactam agents. This transfer process has resulted in penicillin-resistant S. pneumoniae through the acquisition of genes from other naturally occurring penicillin-resistant Streptococcus species. A second important mechanism by which bacteria become resistant to beta-lactam antibiotics is by the production of enzymes capable of inactivating or modifying the drug before it has a chance to exert its effect on the bacteria. View animation to read more.
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Developed and produced by http://www.MechanismsinMedicine.com Animation Description: This patient-friendly animation describes the main role of insulin in the human body. When food is ingested, it travels along the digestive tract where it is broken down into its component nutrients in order to be absorbed into the bloodstream. One such nutrient is glucose, a simple sugar. Glucose gets absorbed by the stomach and intestines and then enters the bloodstream. It travels through the circulation to all body cells. Once absorbed into the bloodstream, glucose circulates causing the blood sugar level to rise. An increased level of blood sugar sends a signal to the pancreatic beta cells, which respond by secreting the hormone insulin into the circulation. Insulin is necessary for glucose to reach and be used by several important target tissues throughout the body. These include the liver, muscle, and adipose tissue. Insulin is necessary to keep blood glucose levels stable in the body. Circulating insulin binds to specific insulin receptors located on the cell membrane of tissue cells throughout the body. Upon binding, a signal is sent to the nucleus of the cell, instructing it to transport glucose channels to the cell surface. These channels allow glucose to enter the cell. Glucose enters the cell through a process called facilitated diffusion.
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Developed and produced for http://www.MechanismsInHematology.com by Mechanisms in Medicine Inc. Animation description: Platelet adhesion and aggregation. In flowing blood, red cells predominate in the axial stream, while the biconvex disc-shaped platelets are marginated along the vessel wall where they are well-positioned to monitor the integrity of the endothelium. The normal endothelium provides a non-adhesive surface to circulating platelets. However, when vessel wall injury occurs, for example, by cutting or severing of a vessel, or as shown here, by a puncture, and there is endothelial damage, the initial response of platelets is that of adhesion to collagen fibres in the exposed subendothelium. Collagen is one of the most thrombogenic components of the subendothelial matrix responsible for the initiation of platelet adhesion. A number of adhesive receptors on the platelet surface membrane interact either directly or indirectly with collagen. Initial binding of platelets is considered to occur via the integrin α2β1 (GPIa-IIa) receptor, which allows for further binding to collagen via the GPVI receptor, initiating transmembrane and, subsequently, intracellular signalling. Adhesion of platelets to the exposed subendothelium is influenced by shear rates. At high shear, α2β1 and GPVI are not sufficient to initiate binding to collagen, and binding of the GPIb-IX-V receptor to von Willebrand factor -- abbreviated here as V.W.F. -- that is immobilized on collagen, becomes essential in platelet adhesion. Platelet adhesion at the site of vessel wall damage initiates activation events that result in aggregation. Adherent platelets undergo a dramatic shape change to an irregular sphere with multiple filipodia spreading on the subendothelium increasing their area of surface contact. Adherent platelets also secrete or release the contents of their storage granules -- the alpha- and dense granules -- by an exocytic process. This provides a high local concentration of effector molecules essential for platelet plug formation at the site of vascular injury. For example, the aggregating agent A.D.P. is released from the dense granules. Platelet activation stimulates the formation of another aggregating agent, thromboxane A2 -- abbreviated here as T.X.A2 -- via the arachidonic acid cascade -- details are shown in Figure 26-5. A.D.P., thromboxane A2 and thrombin bind to specific platelet membrane receptors -- details are shown in Table 26-1 -- and stimulate aggregation on and around the platelets adherent to the subendothelium via receptor-mediated signal transduction events. Aggregation is an active metabolic process: binding of any of the agonists to their respective membrane receptors initiates signalling pathways that ultimately convert integrin αIIbβ3 -- or GPIIb-IIIa - from a low affinity resting state to a high-affinity activated state for binding extracellular soluble ligands such as plasma fibrinogen and von Willebrand factor -- fibrinogen is shown here. The transmission of an intracellular signal leads to disruption of the complex between the cytoplasmic tails of αIIbβ3, followed by a conformational change in its extracellular globular head domains from a bent to an extended state, promoting the binding to fibrinogen and von Willebrand factor. Divalent fibrinogen and multivalent von Willebrand factor function as bridges between αIIbβ3 receptors on adjacent activated platelets, thus allowing platelet aggregation to proceed. In this way, the large and complex metabolic repertoire of platelets allows them to effectively perform their primary physiological role, that of supporting hemostasis upon tissue trauma to form a platelet plug that arrests blood loss from a vascular injury. To learn more, go to http://www.MechanismsInHematology.com -- a freely available, educational resource that combines the clinical expertise of hematologists, oncologists, and related researchers with instructive visuals and animations. Essential concepts pertaining to the science and biology of clinical hematology are presented.
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Another common mechanism of cancer biology is the ability of malignant cells to migrate from their original site to organs throughout the body. This animation provides a closer look at how the EGFR pathway activates and modulates this process of metastasis. This animation is the third part of the series "An Introduction to Cancer Biology".
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As the tumor grows, it eventually reaches a size where it requires additional vasculature in order to sustain continued growth. To achieve this, tumor cells excrete certain proteins that stimulate blood vessel growth into and around the tumor - a process called angiogenesis. This animation is the fourth and final part of the series "An Introduction to Cancer Biology".
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Developed and produced by http://www.MechanismsinMedicine.com Animation Description: This animation represents a visual interpretation of the production of testosterone and is not indicative of clinical effectiveness. The hypothalamus releases gonadotropin-releasing hormone (GnRH) in pulses every 60 to 90 minutes to stimulate the pulsatile release of luteinizing hormone (LH) from the pituitary gland into the bloodstream. LH binds the LH receptor on the Leydig cells of the testes. Binding initiates a cascade of events which include the conversion of cholesterol (depicted as LDL here) to pregnenolone followed by a series of reactions, which convert pregnenolone to testosterone. Testosterone, secreted by the testes, diffuses into the peripheral circulation to be carried to target tissues. In liver, muscle and adipose tissue, testosterone binds directly to its androgen receptor (AR) to exert its biological effect. In skin, hair, the prostate gland and gonadal tissue, testosterone must be converted to dihydrotestosterone (DHT) by 5-alpha-reductase in order to bind the androgen receptor. In bone and brain, testosterone is converted by aromatization to estradiol (E2), which binds the estrogen receptor (E2R) to carry out its effects. There is an accompanying accredited online resource, http://www.ManagingTD.ca that contains the learning materials, as well as videos, animations & an interactive algorithm.
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Developed and produced by http://www.MechanismsinMedicine.com Animation Description: In this animation, we demonstrate the biology of DNA replication leading to bacterial cell division in a gram positive bacterium, such as S. pneumoniae. The DNA is shown as a circular double strand within the bacterial cell. Like the DNA of all living organisms, it contains the unique genetic code for all of the proteins required for bacterial survival. Bacteria replicate by a process known as binary fission whereby one bacterium separates into 2 new daughter cells. However, before this can occur, the bacterium must make an identical copy of its complete circular DNA. DNA replication requires that the two strands of DNA separate so that the genetic code of the bacterium can be read and a new complimentary strand can be created for each of the original strands. To accomplish this, various enzymes known as helicases break the hydrogen bonds between the bases in the two DNA strands, unwind the strands from each other, and stabilize the exposed single strands, preventing them from joining back together. The points at which the two strands of DNA separate to allow replication of DNA are known as replication forks. The enzymes DNA polymerase then move along each strand of DNA, behind each replication fork synthesizing new DNA strands (in red) complementary to the original ones. As the replication forks move forward, positive superhelical twists in the DNA begin to accumulate ahead of them. In order for DNA replication to continue, these superhelical twists must be removed. The bacterial enzyme, DNA gyrase, which is also known as topoisomerase II, is responsible for removing the positive superhelical twists so that DNA replications can procede. DNA gyrase is an essential bacterial enzyme composed of two A and two B subunits which are products of the gyrA and gyrB genes. This enzyme has other important functions which affect the initiation of DNA replication and transcription of many genes. With the combined involvement of these enzymes, an entire duplicate copy of the bacterial genome is produced as the 2 replication forks move in opposite directions around the circular DNA genome. Eventually, as the 2 replication forks meet, 2 new complete chromosomes have been made, each consisting of 1 old and 1 new strand of DNA. This is referred to as semi-conservative replication. In order to allow the 2 new interlinked chromosomes to come apart, another bacterial enzyme is needed which is known as topoisomerase IV. This enzyme is structurally related to DNA gyrase and is coded for by the parC and parE genes. Topoisomerase IV allows for the 2 new inter-linked chromosomes to separate so that they can be segregated into 2 new daughter bacterial cells. Complete separation of bacterial cells Fluoroquinolones. First mechanism of action -- inhibition of DNA gyrase. Fluoroquinolones act by inhibiting the activity of both the DNA gyrase and the topoisomerase IV enzymes. For most gram negative bacteria, DNA gyrase is the primary fluoroquinolone target. Fluoroquinolones have been shown to bind specifically to the complex of DNA gyrase and DNA rather than to DNA gyrase alone. As a result of this binding, quinolones appear to stabilize the enzyme-DNA complexes which in turn results in breaks in the DNA that are fatal to the bacterium. A second mechanism of fluoroquinolone action is shown here. With some exceptions, topoisomerase IV is the primary target of fluoroquinolone action in most gram positive bacteria such as Staphylococci and Streptococci, with DNA gyrase being a secondary target. The separation of 2 new interlinked daughter strands of circular DNA is disrupted. The final result on the bacteria, however, is the same. Bacterial replication is disrupted and the bacterium breaks apart. The relative potency of different fluoroquinolone antibiotics (and thus their spectrum of activity) is dependent in part on their affinity for either DNA gyrase or topoisomerase IV or both. One of the most common mechanisms by which bacteria acquire resistance to fluoroquinolones is by spontaneously occurring mutations in chromosomal genes that alter the target enzymes -- DNA gyrase and topoisomerase IV or both. The frequency with which these spontaneous mutations occurs may be in the range of 10-6. The effect of mutations on the activity of an individual fluoroquinolone will vary depending on the number of mutations, the location of the mutations and which target enzyme is affected. If a mutation occurs (either in the gyrA or gyrB gene) that alters DNA gyrase and results in a reduced affinity of the fluoroquinolone antibiotic for this enzyme, the organism will become resistant. View animation to read more.
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Developed and produced for http://www.MechanismsinMedicine.com Animation Description: Fungi are eukaryotic organisms which possess a unique cell wall and cell membrane that can serve as targets for antifungal agents. Polyene antifungal agents such as Amphotericin B target the fungal cell membrane. Watch this animation for more information.
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This animation is the first part of the series "An Introduction to Cancer Biology", and explains the mechanism of abnormal signal transduction resulting in uncontrolled cell proliferation. This animation also provides an overview of the potential targets of anticancer therapies.
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Apoptosis or "programmed cell death" is a mechanism by which organisms limit the growth and replication of cells. Loss of apoptosis is one of the key mechanisms behind cancer. This animation is the second part of the series "An Introduction to Cancer Biology", and reveals the faulty apoptotic pathways that tumor cells often have.
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Developed and produced by http://www.MechanismsinMedicine.com Animation Description: The DNA is shown as a circular double strand within the bacterial cell. Like the DNA of all living organisms, it contains the unique genetic code for all of the proteins required for bacterial survival. These include the proteins required for reproduction, growth, repair and regulation of metabolism. It also codes for the 3 kinds of RNA that are essential for carrying out protein synthesis. These are known as ribosomal RNA (rRNA), messenger RNA (mRNA) and transfer RNA (tRNA). In order for the bacteria to begin protein synthesis, the double-stranded DNA molecule must first unwind and separate in the region which codes for the specific protein that is to be made. Only one strand of the DNA serves as the template for this process known as transcription. Transcription results in the formation of messenger RNA (mRNA) which is a mirror copy of the DNA segment. Once the strand of mRNA is complete, it will detach from the DNA template and in turn become attached to ribosomes. Bacterial ribosomes are made of a small (30S) and a large (50S) subunit. After the 2 subunits join together around the strand of mRNA, synthesis of the polypeptide chain begins. This step involves the aligning of transfer RNA (tRNA) molecules in sequence along the mRNA. Each tRNA carries a unique amino acid (determined by the sequence of the tRNA) which, when aligned along the mRNA and ribosome, join together to form the polypeptide chain. This step is known as translation. The ribosome will continue to add amino acids to the growing polypeptide chain until it reaches a point along the mRNA that signals it to stop. At this point it releases the finished protein molecule. Macrolide antibiotics such as erythromycin, act as inhibitors of protein synthesis by attaching to the 50S ribosomal subunit. By so doing, they block the ability of the ribosome to synthesize the polypeptide chain. By inhibiting protein synthesis, macrolides are considered bacteriostatic antibiotics. However, at higher concentrations and with lower bacterial density or during rapid bacterial growth, macrolides may be bactericidal. Changes or modifications to the 50S ribosomal subunit (i.e. the target binding site for macrolide antibiotics) will confer resistance to macrolides and sometimes other classes of antibiotics. This type of resistance may be of a high level. This mechanism of resistance is mediated by the erm (erythromycin ribosome methlylation) gene which is found on plasmids or transposons (i.e. small genetic elements which are capable of moving from one bacterium to another and integrating into the host chromosomal DNA). Copies of the erm gene are transported to other bacteria via plasmids or transposons through "pili-like" channels. The erm gene is incorporated into the new bacterial genome. During the process of protein synthesis, this bacterium will transcribe and translate the genetic code of the erm gene resulting in the production of a protein enzyme capable of methylating the 50S ribosomal subunit at a specific position. This altered 50S subunit results in decreased binding affinity for macrolides and other antibiotics such as lincosamides (e.g. clindamycin) and streptogramin type B. This pattern of resistance is referred to as the MLS phenotype. Because the macrolide antibiotic is unable to bind to the 50S ribosomal subunit, it is unable to inhibit protein synthesis and thus the bacteria itself is not harmed, continuing to produce polypeptide chains of amino acids. A second mechanism of bacterial resistance to macrolide antibiotics is mediated by efflux pumps. These efflux pumps are encoded by the mef(A) gene which is a transposable element. Because they confer resistance to only macrolides and not lincosamides or streptogramin B they are referred to as the M phenotype. The efflux pumps are energy-dependent and for S. pneuomoniae result in moderate levels of resistance. These pumps traverse the cell membrane of the bacteria and function to "pump out" the macrolide antibiotic after it has entered the bacterium. It should be noted that for other bacteria such as Staphylococcus aureus for example, a different efflux system which is plasmid-mediated and encoded by the msr(A) gene results in macrolide resistance as well as lincosamide and streptogramin resistance in some cases. Despite the presence of these efflux pumps, macrolide antibiotics continue to enter the bacteria. However, once inside the cytoplasm of the bacteria, these efflux pumps actively remove the macrolide antibiotics before they have a chance to reach their target, the 50S ribosomal subunit and bacterial protein synthesis is unaffected.
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Developed and produced for http://www.MechanismsinMedicine.com Animation Description: Fungi are eukaryotic organisms which possess a unique cell wall and cell membrane that can serve as targets for antifungal agents. Polyene antifungal agents such as Amphotericin B target the fungal cell membrane. Watch this animation for more information.
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Developed and produced for http://www.MDPracticeGuide.com, a CME resource for physicians and healthcare providers. Animation Description: This animation explains the mechanism of action of aminosalicylates used for the treatment of inflammatory bowel disease (IBD). Aminosalicylates include sulfasalazine and 5-aminosalicylic acid (5-ASA). Sulfasalazine, a sulfa drug, inhibits folic acid synthesis. As such, folic acid supplements should be taken with sulfasalazine to reduce the risk of neural tube defects. Sulfasalazine exhibits anti-inflammatory properties when split by gut bacterium into its metabolites: sulfapyridine and 5-ASA (mesalamine). The anti-inflammatory benefits of sulfasalazine, are chiefly derived from 5-ASA, which has fewer side effects than sulfapyridine. As such, administration of 5-ASA alone may be preferred over sulfasalazine. 5-ASA is poorly absorbed by the intestines and systemic circulation, thus most remains in the terminal ileum and colon or is passed in the stool. 5-ASA within the lumen primarily exhibits a topical effect on the colonic epithelium. Absorbed 5-ASA is extensively metabolized to N-acetyl-5-ASA by N-acetyltransferase 1 (NAT1). N-acetyl-5-ASA then binds PPAR-gamma (peroxisome proliferator-activated receptor gamma) a nuclear hormone receptor. Binding of N-acetyl-5-ASA induces the translocation of PPAR-gamma from the cytoplasm to the cell nucleus and a conformational change in PPAR-gamma. This modification permits the recruitment of the co-activator, vitamin D3 receptor-interacting protein (DRIP), which interacts directly with PPAR-gamma. Heterodimerization with the retinoid X receptor (RXR) occurs, resulting in formation of the PPAR-RXR complex, a transcriptional regulator. The PPAR-RXR heterodimer controls transcription by binding a regulatory PPAR-gamma response element (PPRE) and modulating the expression of genes involved in the inflammation process. PPAR-RXR downregulates the nuclear factor kappa B (NF-kappaB) and mitogen-activated protein kinase (MAPK) to reduce production of pro-inflammatory cytokines. This complex also reduces COX-2 activity, leading to a reduction in prostaglandins involved in inflammation. Novel agents with similar mechanisms to 5-ASA, but which target PPAR-gamma more efficiently and report a reduction of adverse events, are currently under investigation. For example the compound, GED-0507-34, exhibits a 100- to 150-fold greater anti-inflammatory effect than 5-ASA. A new generation of 5-ASA, balsalazide, is able to bypass the small intestine and release a high concentration of 5-ASA in the colon.
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This animation describes how NRTI drugs work by incorporating themselves into viral DNA as it is being transcribed, and thus, blocking further extension of the viral DNA chain. Narrated by Dr. Mark Wainberg, Professor of Medicine and of Microbiology at McGill University, Montreal, Quebec, a Canadian AIDS researcher and activist. For more information please visit http://www.AnimatedHIVScience.com
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Developed and produced for http://www.MDPracticeGuide.com, a CME resource for physicians and healthcare providers. Animation Description: Under normal circumstances, bacterial infection results in the release of chemokines that attract circulating neutrophils to the endothelium. This process is known as chemotaxis. A variety of molecules are expressed on the endothelial cell surface that allow the neutrophil to be captured, then roll along the endothelium, then adhere. Following adherence, the neutrophil migrates into the subendothelial tissue to reach the site of infection. The neutrophil engulfs the bacteria and eliminates them via breakdown within the phagosomes — a process known as phagocytosis. In states of hyperglycemia, chemotaxis is reduced. Adherence is also adversely affected. Phagocytosis is also impaired by hyperglycemia. Hyperglycemia also adversely affects the macrophage system. Under normal circumstances, circulating monocytes are attracted to sites of infection, roll, adhere, and then migrate into the subendothelial space. The monocyte then transforms into a macrophage. which is then activated by cytokines released by the bacteria. The activated macrophage then engulfs the bacteria. However, hyperglycemia results in decreased activation of macrophages, thereby arresting the process of macrophage phagocytosis of bacteria. In addition to affecting neutrophil and macrophage function, hyperglycemia also affects the complement cascade. Under situations of normal glycemia, bacteria can activate the complement cascade. Activation of the complement cascade results in the formation of transmembrane protein channels known as membrane attack complex (MAC) in bacterial membrane. Membrane attack complexes make the bacterial membrane porous and the rapid influx of fluid results in the bacterial cell death. Hyperglycemia inhibits the proper activation of the complement cascade, thereby reducing another pathway of the immune system.
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Developed and produced by http://www.MechanismsinMedicine.com Animation Description: Bipolar Disorder encompasses a wide spectrum of symptoms and is classified according to the types of mood episodes exhibited, including: manic, hypomanic, major depressive and mixed episodes. Bipolar I disorder involves a manic or mixed episode in contrast to Bipolar II disorder, which involves at least one major depressive episode and at least one hypomanic episode, but no full manic or mixed episodes. Bipolar Disorder should be differentiated from Major Depressive Disorder (MDD), which is diagnosed when a patient experiences one or more major depressive episodes without any lifetime episodes of hypomania or mania. Depicted here is a life chart (or mood chart), which follows the patient's lifetime history of mood episodes. This permits the identification of mood episodes that are the most prevalent and important to prevent. In this patient, as with many patients with bipolar disorder, depressive episodes become the more prominent aspect of the illness as the person ages. Several morphometric differences have been observed in the brains of Bipolar Disorder patients relative to healthy subjects. White matter hyperintensities and reduction in grey matter volume, identified with MRI, have been described in patients with Bipolar Disorder. Increased ventricular size and decreased frontal cortical area volumes may also be observed in Bipolar Disorder patients. The pathophysiology of Bipolar Disorder encompasses environmental, behavioural, neuronal, cellular, and molecular levels. At the molecular level, aberrant signaling cascades alter synaptic plasticity. Strong evidence supporting the importance of second messenger signaling has come from studying the targets of mood stabilizing drugs such as lithium. GSK-3 and IP3 signaling cascades are known to mediate axonogenesis, synaptogenesis, neuronal growth and cone spreading. Other downstream effects may also be involved. The heritability of bipolar disorder is around 80%. Monozygotic twins are reported to have a higher incidence of developing Bipolar Disorder, approximately 40%, whereas the incidence is only 10% in dizygotic twins. Although the process of developing bipolar disorder likely arises from complex interactions between genes and environmental factors, the specific genes that contribute to this risk are not known with certainty. Variations of several genes have been identified as potential contributors to the pathophysiology of bipolar disorder. Among the identified genes are those associated with serotonin signaling (SLC6A4, TPH2), dopamine signaling (SLC6A3, DRD4), glutamate transmission (DAOA, DTNBP1), and cell maintenance and growth (NRG1, BDNF, DISC1). The most significant environmental triggers of mood episodes among patients with bipolar disorder include use of drugs with mood-altering properties, changes in circadian rhythm, and life stressors. Successful management of bipolar disorder requires particular attention to minimizing the effects of these influences. It is also available on http://www.MDPracticeGuide.com - wholly CME guideline resource dedicated to the needs of busy, practice-based physicians, which spans multiple therapeutic areas.
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This animation describes how PI drugs work by directly binding viral proteases. Narrated by Dr. Mark Wainberg, Professor of Medicine and of Microbiology at McGill University, Montreal, Quebec, a Canadian AIDS researcher and activist. For more information please visit http://www.AnimatedHIVScience.com
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Developed and produced for http://www.MechanismsinMedicine.com Animation Description: When fungi invade the body, dendritic cells play a key role in adaptive immunity. Dendritic cells recognize and bind to fungi and fungal particles by pattern recognition receptors. Watch this animation for more information.
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This animation helps the learner to understand the lipid abnormalities commonly seen in patients with type 2 diabetes. The animation focuses on the major role that elevated plasma free fatty acids (FFAs) play in the development of type 2 diabetes.
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Developed and produced for http://www.MDPracticeGuide.com, a CME resource for physicians and healthcare providers. Animation Description: Cigarette smoking is by far the most common primary risk factor of COPD worldwide. According to global statistics, approximately 210 million people have COPD. By 2030, COPD is predicted to be the fourth leading cause of death worldwide. Epithelial cells lining the airways will respond to smoke inhalation by undergoing cellular changes due to long-term exposure. Over time, chronic irritation and inflammation of the air passages causes small airways disease and parenchymal destruction. Irritation and inflammation of the air passages causes constriction in the bronchi and bronchioles of the lung. In a healthy individual, standing at rest at the foot of a staircase while breathing normally, lung volume is well balanced in terms of: - IRV (Inspirational Reserve Volume); - VT (Tidal Volume); - FRC (Functional Residual Capacity). In the severe COPD patient, lung function is extremely imbalanced with only a tiny capacity for IRV. A patient with severe COPD has a very difficult time managing everyday tasks such as stair climbing. (Spirometry test) The patient is asked to inhale and then forcefully exhale until the lungs are completely emptied via a tube attached to a recording device. The most important values from the spirometry readings are FEV1 and FVC. If the ratio of these values is less than 0.7 then COPD is suspected. More detailed results from spirometry can reveal the stage of COPD in the patient.
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Developed and produced for http://www.MechanismsinMedicine.com Animation Description: Fungi are eukaryotic organisms which possess a unique cell wall and cell membrane that can serve as targets for antifungal agents. The echinocandin class of antifungal agents target the cell wall of fungi. Watch this animation for more information.
Просмотров: 15744 Mechanisms in Medicine
Developed and produced by http://www.MechanismsinMedicine.com Animation description: In this animation, we discuss the concept of physical activity and exercise as they relate to obesity. In humans there is a fine balance between energy intake and energy expenditure. Energy intake is in the form of food, and energy expenditure is in the form of the basal metabolic rate and physical activity. The difference between energy intake and energy expenditure is the net energy balance. If intake exceeds expenditure, then a net positive energy balance occurs. Energy expenditure depends on a number of factors. This includes the starting body weight, the basal metabolic rate and physical activity. With regards to physical activity, there are several key variables including the frequency, intensity, duration and type of activity done. Let us now examine energy consumption. One honey glazed donut is shown which has approximately 300 kilocalories. The energy intake from the consumed donut is equal to the energy consumed by moderate walking for 30-60 minutes, at 3.0 miles per hour. If an individual walks for an hour at 3 miles per hour. They will expend approximately 300 kilocalories, the same as what was contained in the consumed donut. If an individual walks daily for one hour at approximately 3 miles per hour. This type of activity would lead to weight loss. This assumes that the individual does not consume any extra calories and has a net negative energy expenditure. If this activity continues for a period of two to four months, body weight is reduced as depicted. The initial weight loss is the result of a negative net energy balance. The negative energy balance is because energy expenditure exceeds energy intake. After the initial weight loss, the individual continues to do the same type of exercise, that is, 1 hour of moderate walking daily. The chart depicts changes in body weight over time. Individuals are surprised and frustrated that his weight is not continuing to decrease despite regular walking. They have reached a plateau. The reason behind the weight loss pleateau is that with decreased body weight, the basal metabolic rate also decreases. When the basal metabolic rate decreases, there is a decrease in total energy expenditure. If the discouraged individual quits his daily walking exercise. The weight is gained again, at a quicker pace. The weight is re-gained as a result of a positive energy balance being created. Energy expenditure is now less since the physical activity has been stopped. By keeping the same intensity and duration of walking without making any changes in the diet (energy intake) the man would enter a weight maintenance phase. This is characterised by gaining a small amount of weight. The weight maintenance is the result of an energy balance being established within the body, where energy intake essentially equals energy expenditure. If there is no change in energy balance, there will not be any further change in weight. What must be done to end the weight loss plateau? Several options exist to maintain a negative net energy balance. These involve either decreasing energy intake or increasing energy expenditure. Options include: restricting calories further or increasing the frequency, or the intensity or the duration of the exercise. In summary then, weight loss plateau's are expected and can only end with continued exercise and a net negative energy balance. Stopping exercise or increasing calories will lead to weight gain. If one continues to exercise to maintain a net negative energy balance weight loss will be promoted.
Просмотров: 588872 Mechanisms in Medicine
This animation discusses the mechanism of action of JAK inhibitors. To learn more, visit the CME activity “New Frontiers: The Management of IBD: The Future is Bright” at http://bit.ly/2s1FB4b Developed and produced by http://www.MechanismsinMedicine.com
Просмотров: 8896 Mechanisms in Medicine
Developed and produced for http://www.MechanismsinMedicine.com Animation Description: Fungi are eukaryotic organisms and are not related to bacteria. As eukaryotes, they contain membrane bound organelles and possess a cell membrane surrounded by a rigid cell wall. Watch this animation for more information on the unique structural properties of fungi.
Просмотров: 49629 Mechanisms in Medicine
There is a strong connection between type 2 diabetes and dyslipidemia. This animation describes the lipid abnormalities commonly seen in patients with type 2 diabetes: elevated levels of triglycerides, raised small dense LDL levels, increased glycation and oxidation of LDLs and reduction of HDLs. These factors increase the risk of cardiovascular disease.
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This animation reviews the physiological effects of Angiotensin II in the cardiovascular system that contribute to the development of atherosclerosis.
Просмотров: 17320 Mechanisms in Medicine
Developed and produced for http://www.MechanismsinMedicine.com Animation Description: When fungi breach anatomical barriers to invade internal structures, they are recognized by opsonins and phagocytes which initiate the fungal killing process. Watch this animation for more information.
Просмотров: 13660 Mechanisms in Medicine
This animation describes how Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) work by blocking the ability of the viral reverse transcriptase enzyme to convert viral RNA into viral DNA. Narrated by Dr. Mark Wainberg, Professor of Medicine and of Microbiology at McGill University, Montreal, Quebec, a Canadian AIDS researcher and activist. For more information please visit http://www.AnimatedHIVScience.com
Просмотров: 11788 Mechanisms in Medicine
Developed and produced for http://www.MDPracticeGuide.com, a CME resource for physicians and healthcare providers. Animation Description: Primary prevention of stroke requires the management of Atherosclerotic Risk Factors, such as hypertension, diabetes, smoking, and dyslipidemia. As the risk increases, secondary stroke prevention factors include identifying whether or not the patient has suffered from: prior transient ischemic attack (TIA) / Stroke; coronary artery disease (CAD) / peripheral vascular disease (PVD); asymptomatic carotid stenosis; or atrial fibrillation. All patients with ischemic stroke or transient ischemic attack should be on antiplatelet therapy (ASA) for secondary prevention of recurrent stroke unless there is an indication for anticoagulation or a contraindication to ASA. Anticoagulation long term with warfarin is the superior antithrombotic if atrial fibrillation or other definite cardiac source of embolism is identified as the cause of stroke/TIA. Surgical intervention is very effective in the prevention of stroke in symptomatic severe internal carotid artery stenosis. Earlier intervention yields greatest benefit.
Просмотров: 69047 Mechanisms in Medicine
Developed and produced for http://www.MechanismsinMedicine.com Animation Description: Aspergillus species have a wide geographical distribution and are often found in decaying organic matter. The conidia (spores) can be inhaled into the lung air spaces and cause invasive pulmonary aspergillosis. Watch this animation for more information.
Просмотров: 20254 Mechanisms in Medicine
Animation description: The Coagulation Cascade This animation provides an in-depth review of the coagulation cascade. To learn more, go to http://www.MechanismsInHematology.com -- a freely available, educational resource that combines the clinical expertise of hematologists, oncologists, and related researchers with instructive visuals and animations. Essential concepts pertaining to the science and biology of clinical hematology are presented.
Просмотров: 23677 Mechanisms in Medicine
Developed and produced for http://www.MechanismsinMedicine.com This animation helps to understand the pathological steps that lead to the persistence and destructive consequences of synovitis.
Просмотров: 14022 Mechanisms in Medicine
Developed and produced for http://www.MDPracticeGuide.com Animation Description: Animation reviews novel agents for the treatment of Crohn's Disease that target key biologic steps in the inflammatory process. Crohn's disease is an autoimmune disorder characterized by chronic transmural inflammation of the gastrointestinal tract. Inflammation can be seen anywhere along the GI tract but is most often found in the terminal ileum and cecum of the ascending colon. In Crohn's disease, there is a disruption to the normal physiologic balance between immune activated gastrointestinal inflammation and the down regulation of the inflammatory response, thus resulting in chronic inflammation. Leukocyte recruitment is a crucial step in the inflammatory process and involves a cascade of events that consist of the sequential action of molecular signals and adhesion molecules. Blocking any of these steps reduces inflammation by preventing leukocyte accumulation at the site of inflammation. Novel biologic therapies for Crohn's disease are available that target key biologic steps in the inflammatory process such as tumor necrosis factor-alpha (TNF-alpha) and alpha-4 (alpha4) integrin subunits. TNF-alpha is a transmembrane protein produced by macrophages and T-cells. It is released from the membrane of activated cells in response to endotoxins, IL-1, and TNF-alpha. The matrix metalloproteinase, TNF-alpha converting enzyme (TACE), is responsible for cleaving TNF-alpha from the membrane. TNF-alpha binds to TNF receptors on target cells, such as the endothelium. Through endothelial activation, TNF-alpha mediates the upregulation of adhesion molecules, such as E-selectin and VCAM-1, which leads to leukocyte migration and subsequent leukocyte accumulation at the site of inflammation. Anti-TNF-alpha agents are monoclonal antibodies that help to reduce inflammation by binding to TNF-alpha and preventing receptor contact, therefore blocking the pathway to leukocyte migration. The alpha4beta1 and alpha4beta7 surface integrins are selective adhesion molecules that bind to the endothelial cell receptors: VCAM-1 and MAdCAM-1 respectively, facilitating leukocyte adhesion and subsequent migration to areas of inflammation. Anti-alpha4 integrin agents are monoclonal antibodies that bind to the alpha4 subchain and block leukocyte adhesion, thus reducing leukocyte trafficking. These novel agents are advancing the standard of care in Crohn's disease. In select patients these drugs are now being used with the goal of altering the course of disease and bringing about mucosal healing.
Просмотров: 15911 Mechanisms in Medicine
Animation Description: Osteolytic bone lesions are commonly observed in patients with active multiple myeloma. For example, osteolytic bone is characterized by sparse trabeculae and is often associated with brittle bones. These bone lesions result from an imbalance which favors bone resorption and osteoclast activity over that of the osteoblasts. This imbalance is maintained through the activation or repression of multiple signaling pathways that are mediated by a variety of physical interactions between multiple myeloma plasma cells and bone marrow stromal cells. For example, RANK ligand-mediated activation of osteoclasts is enhanced due to increased expression and secretion of RANK ligand from bone marrow stromal cells. Additionally, the secretion of osteoprotegerin by osteoblasts and bone marrow stromal cells is decreased, thereby decreasing suppression of RANK-ligand signaling. Many other cytokines are also released to stimulate osteoclasts and/or inhibit osteoblasts. The identification of patients who may benefit from bone-directed therapy is often based on assessing the levels of some of these cytokines. The class of drugs known as bisphosphonates has been developed to target and inhibit osteoclast activity. Once administered to the patient, bisphosphonates are resorbed by the bone and then taken up by the osteoclasts. Following drug uptake, osteoclast activity is inhibited, usually resulting in apoptosis.
Просмотров: 7160 Mechanisms in Medicine
Animation Description: Candida species can be readily found on the skin, in the genital tract and on the epithelial surface of the gastrointestinal tract. To prevent infection by Candida species, anatomical physical barriers such as the skin and mucous membranes must remain intact without maceration or degradation. Watch this animation for more information.
Просмотров: 7731 Mechanisms in Medicine
Developed and produced for http://www.MechanismsinMedicine.com Animation Description: The initial steps in antifungal host defenses are recognition of invading fungal pathogens and activation of the immune response. This animation reveals how these pathogens make it into our system, and the subsequent immune response our body elicits to get rid of them.
Просмотров: 13437 Mechanisms in Medicine
This animation describes the various types of white blood cells and how they contribute to your body's immunity and defence against infection. Special attention is paid to CD4 cells, the primary target of HIV. Narrated by Dr. Mark Wainberg, Professor of Medicine and of Microbiology at McGill University, Montreal, Quebec, a Canadian AIDS researcher and activist. For more information please visit http://www.AnimatedHIVScience.com
Просмотров: 7575 Mechanisms in Medicine
This animation discusses the mechanism of action of Cell-based Therapies. To learn more, visit the CME activity “New Frontiers: The Management of IBD: The Future is Bright” at http://bit.ly/2s1FB4b Developed and produced by http://www.MechanismsinMedicine.com
Просмотров: 2039 Mechanisms in Medicine
This animation explains the first mechanism of resistance of reverse transcriptase enzyme to some of NRTI drugs, known as nucleoside analogue discrimination. Narrated by Dr. Mark Wainberg, Professor of Medicine and of Microbiology at McGill University, Montreal, Quebec, a Canadian AIDS researcher and activist. For more information please visit http://www.AnimatedHIVScience.com
Просмотров: 5540 Mechanisms in Medicine
Developed and produced by http://www.MechanismsinMedicine.com Animation description: Screening programs aim to identify individuals with cancers at an earlier stage and allow for treatment before growth and spread has occurred. It also allows for detection of pre-cancerous growths such as polyps before the cancer has even developed. Several screening techniques for colon cancer have been used. As cancers grow they may bleed. Small amounts of blood are not necessarily visible within the stool. Testing stool samples for occult blood may indicate the presence of a cancer within the colon. Several trials have shown benefit from the use of this test as a screening tool. This test should be part of a regular exam however it will only detect cancers within the reach of the examining finger [cancers of the mid and lower rectum] Modern scopes have had several improvements. They are thinner and more flexible with better fibre optics allowing sharper images. In addition the instruments allow the use of additional devices for a variety of functions such as snares for polypectomies, forceps for biopsies and other injection devices. Flexible sigmoidoscopes are 60 cm long and are able to detect about 65% of all polyps. Upon the discovery of an adenoma, a colonoscopy is usually required to evaluate the proximal bowel. Case control studies have shown benefit in terms of reduced colon cancer mortality and incidence however they only evaluate the distal end of the colon. A colonoscopy is the gold standard in terms of screening. A scope enters the rectum and is extended through the entire colon. This test will identify almost all cancers and most pre-malignant polyps. It also allows for the removal of smaller growths. This test only has to be repeated every 5-10 years if no polyps are present. Virtual colonoscopy is a new technique that uses computed tomographic or magnetic resonance images to produce computer-generated images of the colon. Patients still require bowel prep and have air insufflated into their colons. In experienced hands, this test is as good as colonoscopy in detecting cancers and larger polyps.
Просмотров: 25122 Mechanisms in Medicine
Developed and produced for http://www.MechanismsinMedicine.com Animation Description: The Infectious Diseases Society of America has developed guidelines for the initial treatment of candidemia and invasive candidiasis. Simple steps for treatment are outlined in this clinical practice algorithm. Successful treatment depends on the ability to differentiate between clinically stable and unstable patients. Watch this animation for more information.
Просмотров: 4271 Mechanisms in Medicine
This animation describes the second mechanism of resistance of reverse transcriptase enzyme to some of NRTI drugs, called primer nucleoside unblocking. Narrated by Dr. Mark Wainberg, Professor of Medicine and of Microbiology at McGill University, Montreal, Quebec, a Canadian AIDS researcher and activist. For more information please visit http://www.AnimatedHIVScience.com
Просмотров: 2759 Mechanisms in Medicine
Developed and produced for http://www.MechanismsinMedicine.com Animation Description: One of the most lethal complications of invasive aspergillosis is dissemination to the brain. The diagnosis is difficult and it has been associated with near 100% mortality, however aggressive antifungal therapy can improve outcomes. Watch this animation for more information.
Просмотров: 2026 Mechanisms in Medicine
This animation describes how mutations in viral proteases can lead to resistance to PI drugs. Narrated by Dr. Mark Wainberg, Professor of Medicine and of Microbiology at McGill University, Montreal, Quebec, a Canadian AIDS researcher and activist. For more information please visit http://www.AnimatedHIVScience.com
Просмотров: 2039 Mechanisms in Medicine
This animation discusses the mechanism of action of SMAD7 Inhibitors. To learn more, visit the CME activity “New Frontiers: The Management of IBD: The Future is Bright” at http://bit.ly/2s1FB4b Developed and produced by http://www.MechanismsinMedicine.com
Просмотров: 946 Mechanisms in Medicine
This animation discusses the etiology of inflammatory bowel disease (IBD). To learn more, visit the CME activity “New Frontiers: The Management of IBD: The Future is Bright” at http://bit.ly/2s1FB4b Developed and produced by http://www.MechanismsinMedicine.com
Просмотров: 2181 Mechanisms in Medicine