The classical signs of inflammation are heat, redness and loss of function. Inflammation is a response, and therefore it is considered as a mechanism of innate immunity, as compared to adaptive immunity. Too little inflammation could lead to tissue destruction by the harmful stimulus. In contrast, chronic inflammation may lead to a host of diseases, such as hay fever, atherosclerosis, rheumatoid arthritis, Inflammation is therefore normally closely regulated by the body. Inflammation can be classified as acute or chronic. Acute inflammation is the response of the body to harmful stimuli and is achieved by the increased movement of plasma. A series of biochemical events propagates and matures the inflammatory response, involving the vascular system, the immune system. Inflammation is not a synonym for infection, Inflammation on the other hand describes purely the bodys immunovascular response, whatever the cause may be. But because of how often the two are correlated, words ending in the suffix -itis are sometimes described as referring to infection.
There are situations where microbial invasion does not result in classic inflammatory response—for example, parasitosis. Acute inflammation is a process, usually appearing within a few minutes or hours. It involves a coordinated and systemic mobilisation response locally of various immune, endocrine, in a normal healthy response, it becomes activated, clears the pathogen and begins a repair process and ceases. It is characterized by five signs, An acronym that may be used to remember the key symptoms is PRISH, for pain, immobility, swelling. Loss of function has multiple causes, Acute inflammation of the lung does not cause pain unless the inflammation involves the parietal pleura, which does have pain-sensitive nerve endings. PAMPs are compounds that are associated with pathogens, but which are distinguishable from host molecules. DAMPs are compounds that are associated with host-related injury and cell damage, at the onset of an infection, burn, or other injuries, these cells undergo activation and release inflammatory mediators responsible for the clinical signs of inflammation.
Vasodilation and its resulting increased blood flow causes the redness and increased heat, increased permeability of the blood vessels results in an exudation of plasma proteins and fluid into the tissue, which manifests itself as swelling. Some of the released mediators such as increase the sensitivity to pain
An antibody, known as an immunoglobulin, is a large, Y-shaped protein produced mainly by plasma cells that is used by the immune system to neutralize pathogens such as bacteria and viruses. The antibody recognizes a molecule of the harmful agent, called an antigen. Each tip of the Y of an antibody contains a paratope that is specific for one particular epitope on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can tag a microbe or a cell for attack by other parts of the immune system. Depending on the antigen, the binding may impede the process causing the disease or may activate macrophages to destroy the foreign substance. The ability of an antibody to communicate with the components of the immune system is mediated via its Fc region. The production of antibodies is the function of the humoral immune system. Antibodies are secreted by B cells of the immune system. In most cases, interaction of the B cell with a T helper cell is necessary to produce full activation of the B cell and, soluble antibodies are released into the blood and tissue fluids, as well as many secretions to continue to survey for invading microorganisms.
Antibodies are glycoproteins belonging to the immunoglobulin superfamily and they constitute most of the gamma globulin fraction of the blood proteins. They are typically made of basic structural units—each with two heavy chains and two small light chains. There are several different types of heavy chains that define the five different types of crystallisable fragments that may be attached to the antigen-binding fragments. The five different types of Fc regions allow antibodies to be grouped into five isotypes, each Fc region of a particular antibody isotype is able to bind to its specific Fc Receptor, thus allowing the antigen-antibody complex to mediate different roles depending on which FcR it binds. The ability of an antibody to bind to its corresponding FcR is further modulated by the structure of the present at conserved sites within its Fc region. The ability of antibodies to bind to FcRs helps to direct the immune response for each different type of foreign object they encounter. For example, IgE is responsible for an allergic response consisting of mast cell degranulation, igEs Fab paratope binds to allergic antigen, for example house dust mite particles, while its Fc region binds to Fc receptor ε.
The allergen-IgE-FcRε interaction mediates allergic signal transduction to induce conditions such as asthma and this region is known as the hypervariable region. Each of these variants can bind to a different antigen and this enormous diversity of antibody paratopes on the antigen-binding fragments allows the immune system to recognize an equally wide variety of antigens
Lithium is a chemical element with the symbol Li and atomic number 3. It is a soft, silver-white metal belonging to the metal group of chemical elements. Under standard conditions, it is the lightest metal and the least dense solid element, like all alkali metals, lithium is highly reactive and flammable. For this reason, it is stored in mineral oil. When cut open, it exhibits a metallic luster, but contact with moist air corrodes the surface quickly to a silvery gray. Because of its reactivity, lithium never occurs freely in nature, and instead, appears only in compounds. Lithium occurs in a number of minerals, but due to its solubility as an ion, is present in ocean water and is commonly obtained from brines. On a commercial scale, lithium is isolated electrolytically from a mixture of lithium chloride, the nucleus of the lithium atom verges on instability, since the two stable lithium isotopes found in nature have among the lowest binding energies per nucleon of all stable nuclides. Because of its relative instability, lithium is less common in the solar system than 25 of the first 32 chemical elements even though the nuclei are very light in atomic weight.
For related reasons, lithium has important links to nuclear physics, the transmutation of lithium atoms to helium in 1932 was the first fully man-made nuclear reaction, and lithium-6 deuteride serves as a fusion fuel in staged thermonuclear weapons. These uses consume more than three quarters of lithium production, Lithium is found in variable amounts in foods, primary food sources are grains and vegetables, in some areas, the drinking water provides significant amounts of the element. Human dietary lithium intakes depend on location and the type of foods consumed, traces of lithium were detected in human organs and fetal tissues already in the late 19th century, leading to early suggestions as to possible specific functions in the organism. However, it took another century until evidence for the essentiality of lithium became available, in studies conducted from the 1970s to the 1990s, rats and goats maintained on low-lithium rations were shown to exhibit higher mortalities as well as reproductive and behavioral abnormalities.
Lithium appears to play an important role during the early fetal development as evidenced by the high lithium contents of the embryo during the early gestational period. The available experimental evidence now appears to be sufficient to accept lithium as essential, the lithium ion Li+ administered as any of several lithium salts has proven to be useful as a mood-stabilizing drug in the treatment of bipolar disorder in humans. Like the other metals, lithium has a single valence electron that is easily given up to form a cation. Because of this, lithium is a conductor of heat and electricity as well as a highly reactive element. Lithiums low reactivity is due to the proximity of its electron to its nucleus
Apoptosis is a process of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes and death and these changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, chromosomal DNA fragmentation, and global mRNA decay. Between 50 and 70 billion cells die each day due to apoptosis in the human adult. For an average child between the ages of 8 and 14, approximately 20 billion to 30 billion cells die a day, for example, the separation of fingers and toes in a developing human embryo occurs because cells between the digits undergo apoptosis. Because apoptosis cannot stop once it has begun, it is a regulated process. Apoptosis can be initiated through one of two pathways, in the intrinsic pathway the cell kills itself because it senses cell stress, while in the extrinsic pathway the cell kills itself because of signals from other cells. Both pathways induce cell death by activating caspases, which are proteases, the two pathways both activate initiator caspases, which activate executioner caspases, which kill the cell by degrading proteins indiscriminately.
Research on apoptosis has increased substantially since the early 1990s, in addition to its importance as a biological phenomenon, defective apoptotic processes have been implicated in a wide variety of diseases. Excessive apoptosis causes atrophy, whereas an insufficient amount results in uncontrolled cell proliferation, some factors like Fas receptors and caspases promote apoptosis, while some members of the Bcl-2 family of proteins inhibit apoptosis. German scientist Karl Vogt was first to describe the principle of apoptosis in 1842, in 1885, anatomist Walther Flemming delivered a more precise description of the process of programmed cell death. However, it was not until 1965 that the topic was resurrected, while studying tissues using electron microscopy, John Foxton Ross Kerr at University of Queensland was able to distinguish apoptosis from traumatic cell death. Following the publication of a paper describing the phenomenon, Kerr was invited to join Alastair R Currie, as well as Andrew Wyllie, in 1972, the trio published a seminal article in the British Journal of Cancer.
Kerr had initially used the term programmed cell necrosis, but in the article, Kerr and Currie credited James Cormack, a professor of Greek language at University of Aberdeen, with suggesting the term apoptosis. Kerr received the Paul Ehrlich and Ludwig Darmstaedter Prize on March 14,2000 and he shared the prize with Boston biologist H. Robert Horvitz. For many years, the apoptosis and programmed cell death were not highly cited. The 2002 Nobel Prize in Medicine was awarded to Sydney Brenner, the genes were identified by studies in the nematode C. elegans and homologues of these genes function in humans to regulate apoptosis. In Greek, apoptosis translates to the falling off of leaves from a tree, professor of Greek language, reintroduced the term for medical use as it had a medical meaning for the Greeks over two thousand years before. Hippocrates used the term to mean the falling off of the bones, galen extended its meaning to the dropping of the scabs
Lead is a chemical element with atomic number 82 and symbol Pb. When freshly cut, it is bluish-white, it tarnishes to a dull gray upon exposure to air and it is a soft and heavy metal with a density exceeding that of most common materials. Lead has the second-highest atomic number of the stable elements. Lead is a relatively unreactive post-transition metal and its weak metallic character is illustrated by its amphoteric nature and tendency to form covalent bonds. Compounds of lead are found in the +2 oxidation state. Exceptions are mostly limited to organolead compounds, like the lighter members of the group, lead exhibits a tendency to bond to itself, it can form chains and polyhedral structures. Lead is easily extracted from its ores and was known to people in Western Asia. A principal ore of lead, often bears silver, Lead production declined after the fall of Rome and did not reach comparable levels again until the Industrial Revolution. Nowadays, global production of lead is about ten million tonnes annually, Lead has several properties that make it useful, high density, low melting point and relative inertness to oxidation.
In the late 19th century, lead was recognized as poisonous, Lead is a neurotoxin that accumulates in soft tissues and bones, damaging the nervous system and causing brain disorders and, in mammals, blood disorders. A lead atom has 82 electrons, arranged in a configuration of 4f145d106s26p2. The combined first and second ionization energies—the total energy required to remove the two 6p electrons—is close to that of tin, leads upper neighbor in group 14. This is unusual since ionization energies generally fall going down a group as an elements outer electrons become more distant from the nucleus, the similarity is caused by the lanthanide contraction—the decrease in element radii from lanthanum to lutetium, and the relatively small radii of the elements after hafnium. The contraction is due to shielding of the nucleus by the lanthanide 4f electrons. The combined first four ionization energies of lead exceed those of tin, for this reason lead, unlike tin, mostly forms compounds in which it has an oxidation state of +2, rather than +4.
Relativistic effects, which become particularly prominent at the bottom of the periodic table, as a result, the 6s electrons of lead become reluctant to participate in bonding, a phenomenon called the inert pair effect. A related outcome is that the distance between nearest atoms in crystalline lead is unusually long, the lighter group 14 elements form stable or metastable allotropes having the tetrahedrally coordinated and covalently bonded diamond cubic structure. The energy levels of their outer s- and p-orbitals are close enough to allow mixing into four hybrid sp3 orbitals
Radiocontrast agents are per definition of drugs, but lack therapeutic effects. Contrast medium is used to enhance the visibility of internal structures in X-ray-based imaging techniques such as computed tomography, radiocontrast agents are typically iodine or barium compounds. Magnetic resonance imaging functions through different principles and thus utilizes different contrast agents and these compounds work by altering the magnetic properties of nearby hydrogen nuclei. Radiocontrast agents used in X-ray examinations can be grouped based on its use, iodine-based contrast media are usually classified as ionic or non-ionic. Both types are used most commonly in radiology due to their relatively harmless interaction with the body, contrast media are primarily used to visualize vessels and changes in tissues on radiography and CT. Contrast media can be used for tests of the tract, uterus. It may cause the patient to feel as if he or she has urinated on him- or herself and it puts a metallic taste in the mouth of the patient.
Modern intravenous contrast agents are based on iodine. This may be either in an organic compound or an ionic compound. Ionic agents were developed first and are still in use depending on the requirements. Organic agents which covalently bind the iodine have fewer side effects as they do not dissociate into component molecules, many of the side effects are due to the hyperosmolar solution being injected. I. e. they deliver more iodine atoms per molecule, the more iodine, the more dense the X-ray effect. Organic iodine molecules used for contrast include iohexol and ioversol and these contrast agents are sold as clear, colorless water solutions, with the concentration usually expressed as mg I/ml. Modern iodinated contrast agents can be used almost anywhere in the body, most often they are used intravenously, but for various purposes they can be used intraarterially and intraabdominally – just about any body cavity or potential space. Iodine contrast agents are used for the following, Angiography Venography VCUG HSG IVU Ionic contrast media typically, non-ionic contrast media have lower osmolality and tend to have fewer side-effects.
Barium sulfate is used in the imaging of the digestive system. The substance exists as a white powder that is made into a slurry with water. Depending on how it is to be administered the compound is mixed with water, thickeners, de-clumping agents, as the barium sulfate doesnt dissolve, this type of contrast agent is an opaque white mixture
An analgesic or painkiller is any member of the group of drugs used to achieve analgesia, relief from pain. Analgesic drugs act in various ways on the peripheral and central nervous systems and they are distinct from anesthetics, which temporarily affect, and in some instances completely eliminate, sensation. Analgesics include paracetamol, the nonsteroidal anti-inflammatory drugs such as the salicylates, when choosing analgesics, the severity and response to other medication determines the choice of agent, the World Health Organization pain ladder specifies mild analgesics as its first step. Topical nonsteroidal anti-inflammatory drugs provided pain relief in common such as muscle sprains. Since the side effects are lesser, topical preparations could be preferred over oral medications in these conditions, each different type of analgesic has its own associated side effects. Drugs for pain are typically classified by chemical structure and they may be classified in other ways. Sometimes they are classified by use for classes of medical condition.
Other times they are sorted by the needs of populations who would use them. They might be listed by availability in an area, perhaps to prevent recommending a drug which is illegal in one place even if it is easily available elsewhere. Paracetamol, known as acetaminophen or APAP, is a used to treat pain. It is typically used for mild to moderate pain, in combination with opioid pain medication, paracetamol is used for more severe pain such as cancer pain and after surgery. It is typically used either by mouth or rectally but is available intravenously, effects last between two and four hours. Paracetamol is classified as a mild analgesic, paracetamol is generally safe at recommended doses. Nonsteroidal anti-inflammatory drugs, are a class that groups together drugs that provide analgesic and antipyretic effects. The most prominent members of group of drugs, aspirin. These drugs have been derived from NSAIDs, the cyclooxygenase enzyme inhibited by NSAIDs was discovered to have at least 2 different versions, COX1 and COX2.
Research suggested most of the effects of NSAIDs to be mediated by blocking the COX1 enzyme. Thus, the COX2 inhibitors were developed to inhibit only the COX2 enzyme and these drugs are equally effective analgesics when compared with NSAIDs, but cause less gastrointestinal hemorrhage in particular
Nonsteroidal anti-inflammatory drug
Nonsteroidal anti-inflammatory drugs are a drug class that groups together drugs that provide analgesic and antipyretic effects, and, in higher doses, anti-inflammatory effects. The term nonsteroidal distinguishes these drugs from steroids, among a range of other effects, have a similar eicosanoid-depressing. First used in 1960, the served to distance new drugs from steroid-related iatrogenic tragedies. The most prominent members of group of drugs are aspirin and naproxen. Paracetamol is generally not considered an NSAID because it has only little anti-inflammatory activity and it treats pain mainly by blocking COX-2 mostly in the central nervous system, but not much in the rest of the body. Most NSAIDs inhibit the activity of cyclooxygenase-1 and cyclooxygenase-2, and thereby the synthesis of prostaglandins, NSAIDs are usually used for the treatment of acute or chronic conditions where pain and inflammation are present. NSAIDs are generally used for the relief of the following conditions, Aspirin.
This is useful for the management of arterial thrombosis and prevention of cardiovascular events. Aspirin inhibits platelet aggregation by inhibiting the action of thromboxane A2, NSAIDs are useful in the management of post-operative dental pain following invasive dental procedures such as dental extraction. When not contra-indicated they are favoured over the use of paracetamol alone due to the effect they provide. When used in combination with paracetamol the analgesic effect has proven to be improved. Use of NSAIDs increases risk of having a range of gastrointestinal problems, when NSAIDs are used for pain management after surgery they cause increased risk of kidney problems. An estimated 10–20% of NSAID patients experience dyspepsia, in the 1990s high doses of prescription NSAIDs were associated with serious upper gastrointestinal adverse events, including bleeding. Over the past decade, deaths associated with gastric bleeding have declined, NSAIDs, like all drugs, may interact with other medications.
For example, concurrent use of NSAIDs and quinolones may increase the risk of quinolones adverse central nervous system effects, there is an argument over the benefits and risks of NSAIDs for treating chronic musculoskeletal pain. Each drug has a profile and balancing the risk of no treatment with the competing potential risks of various therapies is the clinicians responsibility. If a COX-2 inhibitor is taken, a traditional NSAID should not be taken at the same time, in addition, people on daily aspirin therapy must be careful if they use other NSAIDs, as these may inhibit the cardioprotective effects of aspirin. Rofecoxib was shown to significantly fewer gastrointestinal adverse drug reactions compared with naproxen
Renal function, in nephrology, is an indication of the state of the kidney and its role in renal physiology. Glomerular filtration rate describes the rate of filtered fluid through the kidney. Creatinine clearance rate is the volume of plasma that is cleared of creatinine per unit time and is a useful measure for approximating the GFR. Creatinine clearance exceeds GFR due to secretion, which can be blocked by cimetidine. In alternative fashion, overestimation by older serum creatinine methods resulted in an underestimation of creatinine clearance, both GFR and CCr may be accurately calculated by comparative measurements of substances in the blood and urine, or estimated by formulas using just a blood test result. The results of tests are used to assess the excretory function of the kidneys. Staging of chronic disease is based on categories of GFR as well as albuminuria. Dosage of drugs that are excreted primarily via urine may need to be modified based on either GFR or creatinine clearance, most doctors use the plasma concentrations of the waste substances of creatinine and urea, as well as electrolytes, to determine renal function.
These measures are adequate to determine whether a patient is suffering from kidney disease, blood urea nitrogen and creatinine will not be raised above the normal range until 60% of total kidney function is lost. Elevated protein levels in urine mark some kidney disease, the most sensitive marker of proteinuria is elevated urine albumin. Persistent presence of more than 30 mg albumin per gram creatinine in the urine is diagnostic of chronic kidney disease, glomerular filtration rate is the volume of fluid filtered from the renal glomerular capillaries into the Bowmans capsule per unit time. Central to the maintenance of GFR is the differential basal tone of the afferent and efferent arterioles. Glomerular filtration rate is equal to the Clearance Rate when any solute is freely filtered and is neither reabsorbed nor secreted by the kidneys, the rate therefore measured is the quantity of the substance in the urine that originated from a calculable volume of blood. This mass equals the mass filtered at the glomerulus as nothing is added or removed in the nephron, the GFR is typically recorded in units of volume per time, e. g. milliliters per minute mL/min.
G F R = Urine Concentration × Urine Flow Plasma Concentration There are several different techniques used to calculate or estimate the glomerular filtration rate, the above formula only applies for GFR calculation when it is equal to the Clearance Rate. The GFR can be determined by injecting inulin or the inulin-analog sinistrin into the plasma, compared to the MDRD formula, the inulin clearance slightly overestimates the glomerular function. In early stage renal disease, the inulin clearance may remain normal due to hyperfiltration in the remaining nephrons, incomplete urine collection is an important source of error in inulin clearance measurement. GFR can be measured using radioactive substances, in particular Chromium-51
Capillaries are the smallest of a bodys blood vessels that make up the microcirculation. Their endothelial linings are only one layer thick. Lymph capillaries connect with larger vessels to drain lymph collected in the microcirculation. The term angiogenesis denotes the formation of new capillaries from pre-existing blood vessels, blood flows from the heart through arteries, which branch and narrow into arterioles, and branch further into capillaries where nutrients and wastes are exchanged. The capillaries join and widen to become venules, which in turn widen and converge to become veins, capillaries do not function on their own, but instead in a capillary bed, an interweaving network of capillaries supplying organs and tissues. The more metabolically active a cell or environment is, the capillaries are required to supply nutrients. Metarterioles are found primarily in the mesenteric microcirculation and were thought to be present in most or all capillary beds. The physiological mechanisms underlying precapillary resistance is no longer considered to be a result of precapillary sphincters outside of the mesentery organ, lymphatic capillaries are slightly larger in diameter than blood capillaries, and have closed ends.
This structure permits interstitial fluid to flow into them but not out, lymph capillaries have a greater internal oncotic pressure than blood capillaries, due to the greater concentration of plasma proteins in the lymph. However lipid-soluble molecules can diffuse through the endothelial cell membranes along concentration gradients. Tight junctions can be divided into two subtypes, Those with numerous transport vesicles, which are found primarily in skeletal muscles, gonads. Those with few vesicles, which are found in the central nervous system. These capillaries are a constituent of the blood–brain barrier, fenestrated capillaries have pores in the endothelial cells that are spanned by a diaphragm of radially oriented fibrils and allow small molecules and limited amounts of protein to diffuse. In the renal glomerulus there are cells with no diaphragms, called foot processes or pedicels. Both of these types of vessels have continuous basal laminae and are primarily located in the endocrine glands, pancreas.
Sinusoidal capillaries are a type of open-pore capillary, that have larger openings in the endothelium. These types of blood vessels allow red and white cells and various serum proteins to pass. These capillaries lack pinocytotic vesicles, and therefore utilize gaps present in cell junctions to permit transfer between cells, and hence across the membrane
Phenacetin is a pain-relieving and fever-reducing drug, which was widely used between its introduction in 1887 and the 1983 ban imposed by the U. S. Food and Drug Administration. Phenacetin was introduced in 1887 in Elberfeld by German company Bayer and it is known historically to be one of the first non-opioid analgesics without anti-inflammatory properties Its analgesic effects are due to its actions on the sensory tracts of the spinal cord. In addition, phenacetin has a depressant action on the heart and it is an antipyretic, acting on the brain to decrease the temperature set point. It is used to treat arthritis and intercostal neuralgia. It is metabolized in the body as paracetamol, which is a clinically relevant analgesic, the first synthesis was reported in 1878 by Harmon Northrop Morse. Weak mutagen, less mutagenic than phenacetin, an early formulation was Vincents APC in Australia. However the U. S. Food and Drug Administration ordered the withdrawal of drugs containing phenacetin in November 1983, owing to its carcinogenic and it was banned in India.
As a result, some branded, previously phenacetin-based preparations continued to be sold, a popular brand of phenacetin was Roches Saridon, which was reformulated in 1983 to contain propyphenazone and caffeine. Coricidin was reformulated without phenacetin, paracetamol is a metabolite of phenacetin with similar analgesic and antipyretic effects, but the new formulation has not been found to have phenacetins carcinogenicity. Phenacetin is now being used as an agent to adulterate cocaine in the UK and Canada. Due to low-cost phenacetin is used for research into the physical and it is an ideal compound for this type of research Phenacetin, and products containing phenacetin, have been shown in an animal model to have the side effect and after-effect of carcinogenesis. In humans, many reports have implicated products containing phenacetin in urothelial neoplasms. In one prospective series, phenacetin was associated with a risk of death due to urologic or renal diseases, death due to cancers. In addition, people with glucose-6-phosphate dehydrogenase deficiency may experience acute hemolysis, or dissolution of blood cells, acute hemolysis is possible in the case of patients who develop an IgM response to phenacetin leading to immune complexes that bind to erythrocytes in blood.
The erythrocytes are lysed when the complexes activate the complement system, chronic use of phenacetin is known to lead to analgesic nephropathy characterized by renal papillary necrosis. This is a condition which results in destruction of some or all of the renal papillae in the kidneys, one notable death that can possibly be attributed to the use of this drug was that of the aviation pioneer Howard Hughes. He had been using phenacetin extensively for the treatment of chronic pain, carcinogen report from the NIH IARC report Safety data for phenacetin