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
Sulfonamide is a functional group, the basis of several groups of drugs, which are called sulphonamides, sulfa drugs or sulpha drugs. The original antibacterial sulfonamides are synthetic antimicrobial agents that contain the sulfonamide group; some sulfonamides are devoid of antibacterial activity, e.g. the anticonvulsant sultiame. The sulfonylureas and thiazide diuretics are newer drug groups based upon the antibacterial sulfonamides. Allergies to sulfonamide are common; the overall incidence of adverse drug reactions to sulfa antibiotics is 3%, close to penicillin. It is important to make a distinction between sulfa drugs and other sulfur-containing drugs and additives, such as sulfates and sulfites, which are chemically unrelated to the sulfonamide group, do not cause the same hypersensitivity reactions seen in the sulfonamides. Nowadays, while sulfonamides appear in the prescriptions written by doctors in developed countries, sulfonamides are still common antimicrobial medications in developing countries owing to their low price.
In bacteria, antibacterial sulfonamides act as competitive inhibitors of the enzyme dihydropteroate synthase, an enzyme involved in folate synthesis. Sulfonamides are therefore bacteriostatic and inhibit growth and multiplication of bacteria, but do not kill them. Humans, in contrast to bacteria, acquire folate through the diet. Sulfonamides are used to treat allergies and cough, as well as antifungal and antimalarial functions; the moiety is present in other medications that are not antimicrobials, including thiazide diuretics, loop diuretics, acetazolamide and some COX-2 inhibitors. Sulfasalazine, in addition to its use as an antibiotic, is used in the treatment of inflammatory bowel disease. Sulfonamide drugs were the first antibacterials to be used systemically, paved the way for the antibiotic revolution in medicine; the first sulfonamide, trade-named Prontosil, was a prodrug. Experiments with Prontosil began in 1932 in the laboratories of Bayer AG, at that time a component of the huge German chemical trust IG Farben.
The Bayer team believed that coal-tar dyes which are able to bind preferentially to bacteria and parasites might be used to attack harmful organisms in the body. After years of fruitless trial-and-error work on hundreds of dyes, a team led by physician/researcher Gerhard Domagk found one that worked: a red dye synthesized by Bayer chemist Josef Klarer that had remarkable effects on stopping some bacterial infections in mice; the first official communication about the breakthrough discovery was not published until 1935, more than two years after the drug was patented by Klarer and his research partner Fritz Mietzsch. Prontosil, as Bayer named the new drug, was the first medicine discovered that could treat a range of bacterial infections inside the body, it had a strong protective action against infections caused by streptococci, including blood infections, childbed fever, erysipelas, a lesser effect on infections caused by other cocci. However, it had no effect at all in the test tube, exerting its antibacterial action only in live animals.
It was discovered by Bovet, Federico Nitti and J. and Th. Jacques Tréfouël, a French research team led by Ernest Fourneau at the Pasteur Institute, that the drug was metabolized into two pieces inside the body, releasing from the inactive dye portion a smaller, active compound called sulfanilamide; the discovery helped establish the concept of "bioactivation" and dashed the German corporation's dreams of enormous profit. The result was a sulfa craze. For several years in the late 1930s, hundreds of manufacturers produced tens of thousands of tons of myriad forms of sulfa; this and nonexistent testing requirements led to the elixir sulfanilamide disaster in the fall of 1937, during which at least 100 people were poisoned with diethylene glycol. This led to the passage of the Federal Food and Cosmetic Act in 1938 in the United States; as the first and only effective antibiotic available in the years before penicillin, sulfa drugs continued to thrive through the early years of World War II. They are credited with saving the lives of tens of thousands of patients, including Franklin Delano Roosevelt Jr. and Winston Churchill.
Sulfa had a central role in preventing wound infections during the war. American soldiers were issued a first-aid kit containing sulfa pills and powder, were told to sprinkle it on any open wound; the sulfanilamide compound is more active in the protonated form. The drug has low solubility and sometimes can crystallize in the kidneys, due to its first pKa of around 10; this is a painful experience, so patients are told to take the medication with copious amounts of water. Newer analogous compounds prevent this complication because they have a lower pKa, around 5–6, making them more to remain in a soluble form. Many thousands of molecules containing the sulfanilamide structure have been created since its discovery, yielding improved formulations with greater effectiveness and less toxicity. Sulfa drugs are still used for conditions such as acne and urinary tract in
Streptococcus is a genus of gram-positive coccus or spherical bacteria that belongs to the family Streptococcaceae, within the order Lactobacillales, in the phylum Firmicutes. Cell division in streptococci occurs along a single axis, so as they grow, they tend to form pairs or chains that may appear bent or twisted; the term was coined in 1877 by Viennese surgeon Albert Theodor Billroth, by combining the prefix "strepto-", together with the suffix "-coccus" Most streptococci are oxidase-negative and catalase-negative, many are facultative anaerobes. In 1984, many bacteria grouped in the genus Streptococcus were separated out into the genera Enterococcus and Lactococcus. Over 50 species are recognised in this genus; this genus has been found to be part of the salivary microbiome. In addition to streptococcal pharyngitis, certain Streptococcus species are responsible for many cases of pink eye, bacterial pneumonia, endocarditis and necrotizing fasciitis. However, many streptococcal species are not pathogenic, form part of the commensal human microbiota of the mouth, skin and upper respiratory tract.
Streptococci are a necessary ingredient in producing Emmentaler cheese. Species of Streptococcus are classified based on their hemolytic properties. Alpha-hemolytic species cause oxidization of iron in hemoglobin molecules within red blood cells, giving it a greenish color on blood agar. Beta-hemolytic species cause complete rupture of red blood cells. On blood agar, this appears. Gamma-hemolytic species cause no hemolysis. Beta-hemolytic streptococci are further classified by Lancefield grouping, a serotype classification; the 20 described serotypes are named Lancefield groups A to V. This system of classification was developed by Rebecca Lancefield, a scientist at Rockefeller University. In the medical setting, the most important groups are the alpha-hemolytic streptococci S. pneumoniae and Streptococcus viridans group, the beta-hemolytic streptococci of Lancefield groups A and B. Table: Medically relevant streptococci When alpha-hemolysis is present, the agar under the colony will appear dark and greenish due to the conversion of hemoglobin to green biliverdin.
Streptococcus pneumoniae and a group of oral streptococci display alpha-hemolysis. Alpha-hemolysis is termed incomplete hemolysis or partial hemolysis because the cell membranes of the red blood cells are left intact; this is sometimes called green hemolysis because of the color change in the agar. S. pneumoniae, is a leading cause of bacterial pneumonia and occasional etiology of otitis media, sinusitis and peritonitis. Inflammation is thought to be the major cause of how pneumococci cause disease, hence the tendency of diagnoses associated with them to involve inflammation; the viridans streptococci are a large group of commensal bacteria that are either alpha-hemolytic, producing a green coloration on blood agar plates, or nonhemolytic. They possess no Lancefield antigens. Beta hemolysis, sometimes called complete hemolysis, is a complete lysis of red cells in the media around and under the colonies: the area appears lightened and transparent. Streptolysin, an exotoxin, is the enzyme produced by the bacteria which causes the complete lysis of red blood cells.
There are two types of streptolysin: Streptolysin O and streptolysin S. Streptolysin O is an oxygen-sensitive cytotoxin, secreted by most group A Streptococcus, interacts with cholesterol in the membrane of eukaryotic cells, results in beta-hemolysis under the surface of blood agar. Streptolysin S is an oxygen-stable cytotoxin produced by most GAS strains which results in clearing on the surface of blood agar. SLS affects immune cells, including polymorphonuclear leukocytes and lymphocytes, is thought to prevent the host immune system from clearing infection. Streptococcus pyogenes, or GAS, displays beta hemolysis; some weakly beta-hemolytic species cause intense hemolysis when grown together with a strain of Staphylococcus. This is called the CAMP test. Streptococcus agalactiae displays this property. Clostridium perfringens can be identified presumptively with this test. Listeria monocytogenes is positive on sheep's blood agar. Group A S. pyogenes is the causative agent in a wide range of group A streptococcal infections.
These infections may be invasive. The noninvasive infections tend to be less severe; the most common of these infections include impetigo. Scarlet fever is a noninvasive infection, but has not been as common in recent years; the invasive infections caused by group A beta-hemolytic streptococci tend to be more severe and less common. This occurs when the bacterium is able to infect areas where it is not found, such as the blood and the organs; the diseases that may
The Catalans are an iberian/european ethnic group of mediterranean and pyrenean descent, having its roots in the Pyrenees mountains. The only official category of "catalans" is that of the citizens of Catalonia, an autonomous community in Spain and the inhabitants of the Roussillon historical region in southeast France, today the Pyrénées Orientales departments called Catalonia Nord and Pays Catalan in French; some authors extend the word "Catalans" to encompass the inhabitants of all the regions where Catalan language is spoken, namely those from Andorra, the Balearic islands, eastern Aragon and the city of Alghero in Sardinia. These territories are known as the Països Catalans or "Catalan Countries". In 1500 BCE the area, now known as Catalonia was, along with the rest of the Iberian Peninsula, inhabited by Proto-Celtic Urnfield people who brought with them the rite of burning the dead; these Indo-European people were absorbed by the Iberians beginning in 600 BCE in a process that would not be complete until the fourth century BCE.
These groups came under the rule of various invading groups starting with the Phoenicians and Carthaginians, who set up colonies along the coast, including Barcino itself. Following the Punic Wars, the Romans replaced the Carthaginians as the dominant power in the Iberian eastern coast, including parts of Catalonia, by 206 BCE. Rome established Latin as the official language and imparted a distinctly Roman culture upon the local population, which merged with Roman colonists from the Italian peninsula. An early precursor to the Catalan language began to develop from a local form of popular Latin before and during the collapse of the Roman Empire. Various Germanic tribes arrived following nearly six centuries of Roman rule, which had transformed the area into the Roman province of Tarraconensis; the Visigoths established themselves in the fifth century, making their first capital in the Iberian peninsula Barcelona, they would move to Toledo. This continued until 718 when Muslim Arabs conquered the region in order to pass through the Pyrenees into French territory.
With the help of the Frankish, a land border was created known nowadays as Old Catalonia which faced Muslim raids but resisted any kind of settlement from them. "New Catalonia" and its native peoples were in control of the Arab invaders for around a century. The Franks on the other side of the Pyrenees held back the main Muslim raiding army which had penetrated unchallenged as far as central France at the Battle of Tours in 732. Frankish suzerainty was extended over much of present-day Catalonia. Larger wars with the Muslims began in the March of Barcelona which led to the beginnings of the Reconquista by Catalan forces over most of Catalonia by the year 801. Barcelona would become an important center for Christian forces in the Iberian Peninsula. Catalonia emerged from the conflicts in Muslim Spain as a regional power, as Christian rulers entrenched themselves in the region during the Carolingian period. Rulers such as Wilfred the Hairy became masters of a larger territory encompassing Catalonia.
The Crown of Aragón included the Principality of Catalonia and the kingdoms of Aragon and Majorca. The marriage of Isabella I of Castile and Ferdinand II of Aragon was a dynastic union in which the Kingdom of Castille and the Kingdom of Aragon were under the same crown but kept their own laws, power structures and monetary systems. Regional unrest led to conflicts such as the Revolt of the Germanies in Valencia and Majorca, the 1640 revolt in Catalonia known as the Reapers' War; this latter conflict embroiled Spain in a larger war with France as many Catalan nobles allied themselves with Louis XIII. The war continued until 1659 and ended with the Peace of the Pyrenees, which partitioned Catalonia as the northern strip of the March came under French rule, while the rest remained under Spanish hegemony; the Catalan government took sides with the Habsburg pretender against the Bourbon one during the War of the Spanish Succession that started in 1705 and ended in 1714. The Catalan failure to defend the continuation of Habsburg rule in Spain culminated in the surrender of Barcelona on 11 September 1714 which came to be commemorated as Catalonia's National Day.
During the Napoleonic Wars, much of Catalonia was seized by French forces by 1808, as France ruled the entire country of Spain until Napoleon's surrender to Allied Armies. In France, strong assimilationist policies integrated many Catalans into French society, while in Spain a Catalan identity was suppressed in favor of a Spanish national identity; the Catalans regained autonomy during the Spanish Second Republic from 1932 until Francisco Franco's nationalist forces retook Catalonia by 1939. It was not until 1975 and the death of Franco that the Catalans as well as other Spaniards began to regain their right to cultural expression, restarted by the Spanish Constitution of 1978. Since this period, a balance between a sense of local identity versus the broader Spanish one has emerged as the dominant political force in Catalonia; the former tends to advocate for greater autonomy and independence. As a result, there tends to be much fluctuation depending on regional and national politics during a given election cycle.
Given the stronge
Histoplasma capsulatum is a species of dimorphic fungi. Histoplasma capsulatum is "distributed worldwide, except in Antarctica, but most associated with river valleys" and occurs chiefly in the "central and eastern United States" followed by "Central and South America, other areas of the world", it is most prevalent in the Mississippi river valleys. It was discovered by Samuel Taylor Darling in 1906. Histoplasma capsulatum is an ascomycetous fungus related to Blastomyces dermatitidis, it is sexual, its sexual state, Ajellomyces capsulatus, can be produced in culture, though it has not been directly observed in nature. As mentioned above, H. capsulatum groups with B. dermatitidis and the South American pathogen Paracoccidioides brasiliensis in the recognized fungal family Ajellomycetaceae. It is dimorphic and switches from a mould-like growth form in the natural habitat to a small budding yeast form in the warm-blooded animal host. Histoplasma capsulatum has two mating types "+" and "–", as with B. dermatitidis.
The great majority of North American isolates belong to a single genetic type but a study of multiple genes suggests a recombining, sexual population. A recent analysis has suggested that the prevalent North American genetic type and a less common type should be considered separate phylogenetic species, distinct from H. capsulatum isolates obtained in Central and South America and other parts of the world. These entities are temporarily designated NAm1 and NAm2. There is as yet no well established clinical or geographic distinction among these two genetic groups. In its asexual form, the fungus grows as a colonial microfungus similar in macromorphology to B. dermatitidis. A microscopic examination shows a marked distinction: H. capsulatum produces two types of conidia, globose macroconidia, 8–15 µm, with distinctive tuberculate or finger-like cell wall ornamentation, ovoid microconidia, 2–4 µm, which appear smooth or finely roughened. It is not clear whether one or both of these conidial types is more important than the other as the principal main infectious particles.
They form on individual short stalks and become airborne when the colony is disturbed. Ascomata of the sexual state are 80–250 µm, are similar in appearance and anatomy to those described above for B. dermatitidis. The ascospores are minute, averaging 1.5 µm. The budding yeast cells formed in infected tissues are small and are characteristically seen forming in clusters within phagocytic cells, including histiocytes and other macrophages, as well as monocytes. An African phylogenetic species, H. duboisii but not always forms larger yeast cells to 15 µm. Histoplasma capsulatum is "distributed worldwide, except in Antarctica, but most associated with river valleys" and occurs chiefly in the "central and eastern United States" followed by "Central and South America, other areas of the world" It is most prevalent in the Ohio and Mississippi river valleys; the enzootic and endemic zones of H. capsulatum can be divided into core areas, where the fungus occurs in soil or on vegetation contaminated by bird droppings or equivalent organic inputs, peripheral areas, where the fungus occurs rarely in association with soil but is still found abundantly in heavy accumulations of bat or bird guano in enclosed spaces such as caves and hollow trees.
The principal core area for this species includes the valleys of the Mississippi and Potomac rivers in the USA as well as a wide span of adjacent areas extending from Kansas, Illinois and Ohio in the north to Mississippi and Texas in the south. In some areas, such as Kansas City, skin testing with the histoplasmin antigen preparation shows that 80–90 % of the resident population have an antibody reaction to H. capsulatum indicating prior subclinical infection. Northern U. S. states such as Minnesota, New York and Vermont are peripheral areas for histoplasmosis, but have scattered counties where 5–19 % of lifetime residents show exposure to H. capsulatum. One New York county, St. Lawrence county shows exposures over 20%; the distribution of H. capsulatum in Canada is not as well documented as in the US. The St. Lawrence Valley is the best known endemic region based both on case reports and on a number of skin test reaction studies that were done between 1945 and 1970; the Montreal area is a well documented endemic focus, not just in the agricultural regions surrounding the city but within the city itself.
The Mount Royal area in central Montreal the north and east sides of Mt. Royal Park, showed exposure rates between 20 and 50% in schoolchildren and locally lifetime-resident university students. A high rate of 79.3% exposure was shown in St. Thomas, south of London, after 7 local residents had died of histoplasmosis in 1957 Based on numerous small regional studies, histoplasmin skin test reactors form ca. 10–50 % of the population in much of southern Ontario and in Quebec’s St. Lawrence Valley, ca. 5% in southern Manitoba and some northerly parts of Quebec, ca. 1% in Nova Scotia. Exposure of aboriginal Canadians occurs remarkably far north in Quebec, but has not been reported in similar boreal biogeoclimatic zones in many other parts of Canada, and remarkably, a cluster of four indigenously acquired cases of histoplasmosis was shown to be associated with a golf course in suburban Edmonton, Alberta. Examination suggested that local soil was the sourc