The retroperitoneal space is the anatomical space in the abdominal cavity behind the peritoneum. It has no specific delineating anatomical structures. Organs are retroperitoneal. Structures that are not suspended by mesentery in the abdominal cavity and that lie between the parietal peritoneum and abdominal wall are classified as retroperitoneal; the retroperitoneum can be further subdivided into the following: Perirenal space Anterior pararenal space Posterior pararenal space Structures that lie behind the peritoneum are termed "retroperitoneal". Organs that were once suspended within the abdominal cavity by mesentery but migrated posterior to the peritoneum during the course of embryogenesis to become retroperitoneal are considered to be secondarily retroperitoneal organs. Retroperitoneal, meaning the structures were retroperitoneal during the entirety of development: urinary adrenal glands kidneys ureter circulatory aorta inferior vena cava anal canal Secondarily retroperitoneal, meaning the structures were suspended in mesentery and migrated behind the peritoneum during developmentthe duodenum, except for the proximal first segment, intraperitoneal ascending and descending portions of the colon pancreas Perirenal SpaceBounded by the anterior and posterior leafs of the renal fascia.
It contains the following structures: Adrenal gland Kidney Renal vesselsAnterior pararenal spaceBounded by the posterior layer of peritoneum and the anterior leaf of the renal fascia. It contains the following structures: Pancreas Ascending and descending colon duodenumPosterior pararenal spaceBounded by the posterior leaf of the renal fascia and the muscles of the posterior abdominal wall, it contains only fat. Bleeding from a blood vessel or structure in the retroperitoneal such as the aorta or inferior vena cava into the retroperitoneal space can lead to a retroperitoneal hemorrhage. Retroperitoneal fibrosis Retroperitoneal lymph node dissection Intraperitoneal
Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the gram-staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall sandwiched between an inner cytoplasmic cell membrane and a bacterial outer membrane. Gram-negative bacteria are found everywhere, in all environments on Earth that support life; the gram-negative bacteria include the model organism Escherichia coli, as well as many pathogenic bacteria, such as Pseudomonas aeruginosa, Neisseria gonorrhoeae, Chlamydia trachomatis, Yersinia pestis. They are an important medical challenge, as their outer membrane protects them from many antibiotics. Additionally, the outer leaflet of this membrane comprises a complex lipopolysaccharide whose lipid A component can cause a toxic reaction when these bacteria are lysed by immune cells; this toxic reaction can include fever, an increased respiratory rate, low blood pressure — a life-threatening condition known as septic shock.
Several classes of antibiotics have been designed to target gram-negative bacteria, including aminopenicillins, ureidopenicillins, beta-lactam-betalactamase combinations, Folate antagonists and carbapenems. Many of these antibiotics cover gram positive organisms; the drugs that target gram negative organisms include aminoglycosides and Ciprofloxacin. Gram-negative bacteria display these characteristics: An inner cell membrane is present A thin peptidoglycan layer is present Has outer membrane containing lipopolysaccharides in its outer leaflet and phospholipids in the inner leaflet Porins exist in the outer membrane, which act like pores for particular molecules Between the outer membrane and the cytoplasmic membrane there is a space filled with a concentrated gel-like substance called periplasm The S-layer is directly attached to the outer membrane rather than to the peptidoglycan If present, flagella have four supporting rings instead of two Teichoic acids or lipoteichoic acids are absent Lipoproteins are attached to the polysaccharide backbone Some contain Braun's lipoprotein, which serves as a link between the outer membrane and the peptidoglycan chain by a covalent bond Most, with few exceptions, do not form spores Along with cell shape, gram-staining is a rapid diagnostic tool and once was used to group species at the subdivision of Bacteria.
The kingdom Monera was divided into four divisions based on gram-staining: Firmacutes, Gracillicutes and Mendocutes. Since 1987, the monophyly of the gram-negative bacteria has been disproven with molecular studies; however some authors, such as Cavalier-Smith still treat them as a monophyletic taxon and refer to the group as a subkingdom "Negibacteria". Bacteria are traditionally classified based on their gram-staining response into the gram-positive and gram-negative groups, it was traditionally thought that the groups represent lineages, i.e. the extra membrane only evoved once, such that gram-negative bacteria are more related to one another than to any gram-positive bacteria. While this is true, the classification system breaks down in some cases, with lineage groupings not matching the staining result. Thus, gram-staining cannot be reliably used to assess familial relationships of bacteria. Staining gives reliable information about the composition of the cell membrane, distinguishing between the presence or absence of an outer lipid membrane.
Of these two structurally distinct groups of prokaryotic organisms, monoderm prokaryotes are thought to be ancestral. Based upon a number of different observations including that the gram-positive bacteria are the major reactors to antibiotics and that gram-negative bacteria are, in general, resistant to them, it has been proposed that the outer cell membrane in gram-negative bacteria evolved as a protective mechanism against antibiotic selection pressure; some bacteria such as Deinococcus, which stain gram-positive due to the presence of a thick peptidoglycan layer, but possess an outer cell membrane are suggested as intermediates in the transition between monoderm and diderm bacteria. The diderm bacteria can be further differentiated between simple diderms lacking lipopolysaccharide; the conventional LPS-diderm group of gram-negative bacteria are uniquely identified by a few conserved signature indel in the HSP60 protein. In addition, a number of bacterial taxa that are either part of the phylum Firmicutes or branches in its proximity are found to possess a diderm cell structure.
They lack the GroEL signature. The presence of this CSI in all se
Inflammation is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, is a protective response involving immune cells, blood vessels, molecular mediators. The function of inflammation is to eliminate the initial cause of cell injury, clear out necrotic cells and tissues damaged from the original insult and the inflammatory process, initiate tissue repair; the five classical signs of inflammation are heat, redness and loss of function. Inflammation is a generic response, therefore it is considered as a mechanism of innate immunity, as compared to adaptive immunity, specific for each pathogen. Too little inflammation could lead to progressive tissue destruction by the harmful stimulus and compromise the survival of the organism. In contrast, chronic inflammation may lead to a host of diseases, such as hay fever, atherosclerosis, rheumatoid arthritis, cancer. Inflammation is therefore closely regulated by the body. Inflammation can be classified as either chronic.
Acute inflammation is the initial response of the body to harmful stimuli and is achieved by the increased movement of plasma and leukocytes from the blood into the injured tissues. A series of biochemical events propagates and matures the inflammatory response, involving the local vascular system, the immune system, various cells within the injured tissue. Prolonged inflammation, known as chronic inflammation, leads to a progressive shift in the type of cells present at the site of inflammation, such as mononuclear cells, is characterized by simultaneous destruction and healing of the tissue from the inflammatory process. Inflammation is not a synonym for infection. Infection describes the interaction between the action of microbial invasion and the reaction of the body's inflammatory response—the two components are considered together when discussing an infection, the word is used to imply a microbial invasive cause for the observed inflammatory reaction. Inflammation on the other hand describes purely the body's immunovascular response, whatever the cause may be.
But because of how the two are correlated, words ending in the suffix -itis are sometimes informally described as referring to infection. For example, the word urethritis means only "urethral inflammation", but clinical health care providers discuss urethritis as a urethral infection because urethral microbial invasion is the most common cause of urethritis, it is useful to differentiate inflammation and infection because there are typical situations in pathology and medical diagnosis where inflammation is not driven by microbial invasion – for example, trauma and autoimmune diseases including type III hypersensitivity. Conversely, there is pathology where microbial invasion does not cause the classic inflammatory response – for example, parasitosis or eosinophilia. Acute inflammation is a short-term process appearing within a few minutes or hours and begins to cease upon the removal of the injurious stimulus, it involves a coordinated and systemic mobilization response locally of various immune and neurological mediators of acute inflammation.
In a normal healthy response, it becomes activated, clears the pathogen and begins a repair process and ceases. It is characterized by five cardinal signs:An acronym that may be used to remember the key symptoms is "PRISH", for pain, immobility and heat; the traditional names for signs of inflammation come from Latin: Dolor Calor Rubor Tumor Functio laesa The first four were described by Celsus, while loss of function was added by Galen. However, the addition of this fifth sign has been ascribed to Thomas Sydenham and Virchow. Redness and heat are due to increased blood flow at body core temperature to the inflamed site. 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; the process of acute inflammation is initiated by resident immune cells present in the involved tissue resident macrophages, dendritic cells, Kupffer cells and mast cells. These cells possess surface receptors known as pattern recognition receptors, which recognize two subclasses of molecules: pathogen-associated molecular patterns and damage-associated molecular patterns.
PAMPs are compounds that are associated with various pathogens, but which are distinguishable from host molecules. DAMPs are compounds that are associated with host-related 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 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 bradykinin increase the sensitivity to pain. The mediator molecules alter the blood vessels to
The lymphatic system is part of the vascular system and an important part of the immune system, comprising a large network of lymphatic vessels that carry a clear fluid called lymph directionally towards the heart. The lymphatic system was first described in the seventeenth century independently by Olaus Rudbeck and Thomas Bartholin. Unlike the circulatory system, the lymphatic system is not a closed system; the human circulatory system processes an average of 20 litres of blood per day through capillary filtration, which removes plasma while leaving the blood cells. 17 litres of the filtered plasma is reabsorbed directly into the blood vessels, while the remaining three litres remain in the interstitial fluid. One of the main functions of the lymph system is to provide an accessory return route to the blood for the surplus three litres; the other main function is that of defense in the immune system. Lymph is similar to blood plasma: it contains lymphocytes, it contains waste products and cellular debris together with bacteria and proteins.
Associated organs composed of lymphoid tissue are the sites of lymphocyte production. Lymphocytes are concentrated in the lymph nodes; the spleen and the thymus are lymphoid organs of the immune system. The tonsils are lymphoid organs that are associated with the digestive system. Lymphoid tissues contain lymphocytes, contain other types of cells for support; the system includes all the structures dedicated to the circulation and production of lymphocytes, which includes the bone marrow, the lymphoid tissue associated with the digestive system. The blood does not come into direct contact with the parenchymal cells and tissues in the body, but constituents of the blood first exit the microvascular exchange blood vessels to become interstitial fluid, which comes into contact with the parenchymal cells of the body. Lymph is the fluid, formed when interstitial fluid enters the initial lymphatic vessels of the lymphatic system; the lymph is moved along the lymphatic vessel network by either intrinsic contractions of the lymphatic passages or by extrinsic compression of the lymphatic vessels via external tissue forces, or by lymph hearts in some animals.
The organization of lymph nodes and drainage follows the organization of the body into external and internal regions. The lymph vessels empty into the lymphatic ducts, which drain into one of the two subclavian veins, near their junction with the internal jugular veins; the lymphatic system consists of lymphatic organs, a conducting network of lymphatic vessels, the circulating lymph. The primary or central lymphoid organs generate lymphocytes from immature progenitor cells; the thymus and the bone marrow constitute the primary lymphoid organs involved in the production and early clonal selection of lymphocyte tissues. Bone marrow is responsible for both the creation of T cells and the production and maturation of B cells. From the bone marrow, B cells join the circulatory system and travel to secondary lymphoid organs in search of pathogens. T cells, on the other hand, travel from the bone marrow to the thymus. Mature T cells join B cells in search of pathogens; the other 95 % of T cells begin a process of a form of programmed cell death.
Secondary or peripheral lymphoid organs, which include lymph nodes and the spleen, maintain mature naive lymphocytes and initiate an adaptive immune response. The peripheral lymphoid organs are the sites of lymphocyte activation by antigens. Activation leads to clonal affinity maturation. Mature lymphocytes recirculate between the blood and the peripheral lymphoid organs until they encounter their specific antigen. Secondary lymphoid tissue provides the environment for the foreign or altered native molecules to interact with the lymphocytes, it is exemplified by the lymph nodes, the lymphoid follicles in tonsils, Peyer's patches, adenoids, etc. that are associated with the mucosa-associated lymphoid tissue. In the gastrointestinal wall the appendix has mucosa resembling that of the colon, but here it is infiltrated with lymphocytes. Tertiary lymphoid organs are abnormal lymph node–like structures that form in peripheral tissues at sites of chronic inflammation, such as chronic infection, transplanted organs undergoing graft rejection, some cancers, autoimmune and autoimmune-related diseases.
TLOs are regulated differently from the normal process whereby lymphoid tissues are formed during ontogeny, being dependent on cytokines and hematopoietic cells, but still drain interstitial fluid and transport lymphocytes in response to the same chemical messengers and gradients. TLOs contains far fewer lymphocytes, assumes an immune role only when challenged with antigens that result in inflammation, it achieves this by importing the lymphocytes from lymph. The thymus is a primary lymphoid organ and the site of maturation for T cells, the lymphocytes of the adaptive immune system; the thymus increases in size from birth in response to postnatal antigen stimulation to puberty and regresses thereafter. The loss or lack of the thymus results in severe immunodeficiency and subsequent high susceptibility to infection. In most species, the thymus consists of lobules divided by septa which are made up of epithelium and is therefore an epithelial organ. T cells mature from
An anaerobic organism or anaerobe is any organism that does not require oxygen for growth. It may react negatively or die if free oxygen is present. (In contrast, an aerobic organism is an organism that requires an oxygenated environment. Anaerobes may be multicellular. In his letter of 14 June 1680 to The Royal Society, Antonie van Leeuwenhoek described an experiment he carried out by filling two identical glass tubes about halfway with crushed pepper powder, to which some clean rain water was added. Van Leeuwenhoek left the other glass tube open. Several days he discovered in the open glass tube ‘a great many little animalcules, of divers sort having its own particular motion.’ Not expecting to see any life in the sealed glass tube, Van Leeuwenhoek saw to his surprise ‘a kind of living animalcules that were round and bigger than the biggest sort that I have said were in the other water.’ The conditions in the sealed tube had become quite anaerobic owing to consumption of oxygen by aerobic microorganisms.
In 1913 Martinus Beijerinck repeated Van Leeuwenhoek's experiment and identified Clostridium butyricum as a prominent anaerobic bacterium in the sealed pepper infusion tube liquid. Beijerinck commented:'We thus come to the remarkable conclusion that, beyond doubt, Van Leeuwenhoek in his experiment with the closed tube had cultivated and seen genuine anaerobic bacteria, which would happen again only after 200 years, namely about 1862 by Pasteur; that Leeuwenhoek, one hundred years before the discovery of oxygen and the composition of air, was not aware of the meaning of his observations is understandable. But the fact that in the closed tube he observed an increased gas pressure caused by fermentative bacteria and in addition saw the bacteria, prove in any case that he not only was a good observer, but was able to design an experiment from which a conclusion could be drawn.' For practical purposes, there are three categories of anaerobe: Obligate anaerobes, which are harmed by the presence of oxygen.
Two examples of obligate anaerobes are Clostridium botulinum and the bacteria which live near hydrothermal vents on the deep-sea ocean floor. Aerotolerant organisms, which cannot use oxygen for growth, but tolerate its presence. Facultative anaerobes, which can grow without oxygen but use oxygen if it is present; some obligate anaerobes use fermentation. Aerotolerant organisms are fermentative. In the presence of oxygen, facultative anaerobes use aerobic respiration. There are many anaerobic fermentative reactions. Fermentative anaerobic organisms use the lactic acid fermentation pathway: C6H12O6 + 2 ADP + 2 phosphate → 2 lactic acid + 2 ATPThe energy released in this equation is 150 kJ per mol, conserved in regenerating two ATP from ADP per glucose; this is only 5 % of the energy per sugar molecule. Plants and fungi in general use alcohol fermentation when oxygen becomes limiting: C6H12O6 + 2 ADP + 2 phosphate → 2 C2H5OH + 2 CO2↑ + 2 ATPThe energy released is about 180 kJ per mol, conserved in regenerating two ATP from ADP per glucose.
Anaerobic bacteria and archaea use these and many other fermentative pathways, e.g. propionic acid fermentation, butyric acid fermentation, solvent fermentation, mixed acid fermentation, butanediol fermentation, Stickland fermentation, acetogenesis, or methanogenesis. Since normal microbial culturing occurs in atmospheric air, an aerobic environment, the culturing of anaerobes poses a problem. Therefore, a number of techniques are employed by microbiologists when culturing anaerobic organisms, for example, handling the bacteria in a glovebox filled with nitrogen or the use of other specially sealed containers, or techniques such as injection of the bacteria into a dicot plant, an environment with limited oxygen; the GasPak System is an isolated container that achieves an anaerobic environment by the reaction of water with sodium borohydride and sodium bicarbonate tablets to produce hydrogen gas and carbon dioxide. Hydrogen reacts with oxygen gas on a palladium catalyst to produce more water, thereby removing oxygen gas.
The issue with the Gaspak method is that an adverse reaction can take place where the bacteria may die, why a thioglycollate medium should be used. The thioglycollate supplies a medium mimicking that of a dicot, thus providing not only an anaerobic environment but all the nutrients needed for the bacteria to thrive. Except for three species of anaerobic loricifera, all known complex multicellular life is aerobic, i.e. needs oxygen to survive. In 2010 three species of anaerobic loricifera were discovered in the hypersaline anoxic L'Atalante basin at the bottom of the Mediterranean Sea, they lack mitochondria which contain the oxidative phosphorylation pathway, which in all other animals combines oxygen with glucose to produce metabolic energy, thus they consume no oxygen. Instead these loricifera derive their energy from hydrogen using hydrogenosomes; some organisms metabolise using glycogen, for example the Nereid s and some polychaetes, or the juvenile form of the pork parasite Trichinella spiralis which causes trichinosis
Gram-positive bacteria are bacteria that give a positive result in the Gram stain test, traditionally used to classify bacteria into two broad categories according to their cell wall. Gram-positive bacteria take up the crystal violet stain used in the test, appear to be purple-coloured when seen through a microscope; this is because the thick peptidoglycan layer in the bacterial cell wall retains the stain after it is washed away from the rest of the sample, in the decolorization stage of the test. Gram-negative bacteria cannot retain the violet stain after the decolorization step, their peptidoglycan layer is much thinner and sandwiched between an inner cell membrane and a bacterial outer membrane, causing them to take up the counterstain and appear red or pink. Despite their thicker peptidoglycan layer, gram-positive bacteria are more receptive to certain cell wall targeting antibiotics than gram-negative bacteria, due to the absence of the outer membrane. In general, the following characteristics are present in gram-positive bacteria: Cytoplasmic lipid membrane Thick peptidoglycan layer Teichoic acids and lipoids are present, forming lipoteichoic acids, which serve as chelating agents, for certain types of adherence.
Peptidoglycan chains are cross-linked to form rigid cell walls by a bacterial enzyme DD-transpeptidase. A much smaller volume of periplasm than that in gram-negative bacteria. Only some species have a capsule consisting of polysaccharides. Only some species are flagellates, when they do have flagella, have only two basal body rings to support them, whereas gram-negative have four. Both gram-positive and gram-negative bacteria have a surface layer called an S-layer. In gram-positive bacteria, the S-layer is attached to the peptidoglycan layer. Gram-negative bacteria's S-layer is attached directly to the outer membrane. Specific to gram-positive bacteria is the presence of teichoic acids in the cell wall; some of these are lipoteichoic acids, which have a lipid component in the cell membrane that can assist in anchoring the peptidoglycan. Along with cell shape, Gram staining is a rapid method used to differentiate bacterial species; such staining, together with growth requirement and antibiotic susceptibility testing, other macroscopic and physiologic tests, forms the full basis for classification and subdivision of the bacteria.
The kingdom Monera was divided into four divisions based on Gram staining: Firmicutes, Gracilicutes and Mendocutes. Based on 16S ribosomal RNA phylogenetic studies of the late microbiologist Carl Woese and collaborators and colleagues at the University of Illinois, the monophyly of the gram-positive bacteria was challenged, with major implications for the therapeutic and general study of these organisms. Based on molecular studies of the 16S sequences, Woese recognised twelve bacterial phyla. Two of these were both gram-positive and were divided on the proportion of the guanine and cytosine content in their DNA; the high G + C phylum was made up of the Actinobacteria and the low G + C phylum contained the Firmicutes. The Actinobacteria include the Corynebacterium, Mycobacterium and Streptomyces genera; the Firmicutes, have a 45 -- 60 % GC content. Although bacteria are traditionally divided into two main groups, gram-positive and gram-negative, based on their Gram stain retention property, this classification system is ambiguous as it refers to three distinct aspects, which do not coalesce for some bacterial species.
The gram-positive and gram-negative staining response is not a reliable characteristic as these two kinds of bacteria do not form phylogenetic coherent groups. However, although Gram staining response is an empirical criterion, its basis lies in the marked differences in the ultrastructure and chemical composition of the bacterial cell wall, marked by the absence or presence of an outer lipid membrane. All gram-positive bacteria are bounded by a single-unit lipid membrane, and, in general, they contain a thick layer of peptidoglycan responsible for retaining the Gram stain. A number of other bacteria—that are bounded by a single membrane, but stain gram-negative due to either lack of the peptidoglycan layer, as in the Mycoplasmas, or their inability to retain the Gram stain because of their cell wall composition—also show close relationship to the Gram-positive bacteria. For the bacterial cells bounded by a single cell membrane, the term "monoderm bacteria" or "monoderm prokaryotes" has been proposed.
In contrast to gram-positive bacteria, all archetypical gram-negative bacteria are bounded by a cytoplasmic membrane and an outer cell membrane. The presence of inner and outer cell membranes defines a new compartment in these cells: the periplasmic space or the periplasmic compartment; these bacteria have been designated as "diderm bacteria." The distinction between the monoderm and diderm bacteria is supported by conserved signature indels in a number of important proteins. Of these two structurally distinct groups of bacteria, monoderms are indicated to be ancestral. Based upon a number of observations including that the gram-positive bacteria are the major producers of antibiotics and that, in general, gram-negative bacteria are resistant to them, it h
International Standard Serial Number
An International Standard Serial Number is an eight-digit serial number used to uniquely identify a serial publication, such as a magazine. The ISSN is helpful in distinguishing between serials with the same title. ISSN are used in ordering, interlibrary loans, other practices in connection with serial literature; the ISSN system was first drafted as an International Organization for Standardization international standard in 1971 and published as ISO 3297 in 1975. ISO subcommittee TC 46/SC 9 is responsible for maintaining the standard; when a serial with the same content is published in more than one media type, a different ISSN is assigned to each media type. For example, many serials are published both in electronic media; the ISSN system refers to these types as electronic ISSN, respectively. Conversely, as defined in ISO 3297:2007, every serial in the ISSN system is assigned a linking ISSN the same as the ISSN assigned to the serial in its first published medium, which links together all ISSNs assigned to the serial in every medium.
The format of the ISSN is an eight digit code, divided by a hyphen into two four-digit numbers. As an integer number, it can be represented by the first seven digits; the last code digit, which may be 0-9 or an X, is a check digit. Formally, the general form of the ISSN code can be expressed as follows: NNNN-NNNC where N is in the set, a digit character, C is in; the ISSN of the journal Hearing Research, for example, is 0378-5955, where the final 5 is the check digit, C=5. To calculate the check digit, the following algorithm may be used: Calculate the sum of the first seven digits of the ISSN multiplied by its position in the number, counting from the right—that is, 8, 7, 6, 5, 4, 3, 2, respectively: 0 ⋅ 8 + 3 ⋅ 7 + 7 ⋅ 6 + 8 ⋅ 5 + 5 ⋅ 4 + 9 ⋅ 3 + 5 ⋅ 2 = 0 + 21 + 42 + 40 + 20 + 27 + 10 = 160 The modulus 11 of this sum is calculated. For calculations, an upper case X in the check digit position indicates a check digit of 10. To confirm the check digit, calculate the sum of all eight digits of the ISSN multiplied by its position in the number, counting from the right.
The modulus 11 of the sum must be 0. There is an online ISSN checker. ISSN codes are assigned by a network of ISSN National Centres located at national libraries and coordinated by the ISSN International Centre based in Paris; the International Centre is an intergovernmental organization created in 1974 through an agreement between UNESCO and the French government. The International Centre maintains a database of all ISSNs assigned worldwide, the ISDS Register otherwise known as the ISSN Register. At the end of 2016, the ISSN Register contained records for 1,943,572 items. ISSN and ISBN codes are similar in concept. An ISBN might be assigned for particular issues of a serial, in addition to the ISSN code for the serial as a whole. An ISSN, unlike the ISBN code, is an anonymous identifier associated with a serial title, containing no information as to the publisher or its location. For this reason a new ISSN is assigned to a serial each time it undergoes a major title change. Since the ISSN applies to an entire serial a new identifier, the Serial Item and Contribution Identifier, was built on top of it to allow references to specific volumes, articles, or other identifiable components.
Separate ISSNs are needed for serials in different media. Thus, the print and electronic media versions of a serial need separate ISSNs. A CD-ROM version and a web version of a serial require different ISSNs since two different media are involved. However, the same ISSN can be used for different file formats of the same online serial; this "media-oriented identification" of serials made sense in the 1970s. In the 1990s and onward, with personal computers, better screens, the Web, it makes sense to consider only content, independent of media; this "content-oriented identification" of serials was a repressed demand during a decade, but no ISSN update or initiative occurred. A natural extension for ISSN, the unique-identification of the articles in the serials, was the main demand application. An alternative serials' contents model arrived with the indecs Content Model and its application, the digital object identifier, as ISSN-independent initiative, consolidated in the 2000s. Only in 2007, ISSN-L was defined in the