Echinocandins are a new class of antifungal drugs that inhibit the synthesis of β-glucan in the fungal cell wall via noncompetitive inhibition of the enzyme 1,3-β glucan synthase. The class has been termed the "penicillin of antifungals," along with the related papulacandins, as their mechanism of action resembles that of penicillin in bacteria. Β-glucans are carbohydrate polymers that are cross-linked with other fungal cell wall components, equivalent to bacterial peptidoglycan. Caspofungin and anidulafungin are semisynthetic echinocandin derivatives with clinical use due to their solubility, antifungal spectrum, pharmacokinetic properties. Drugs and drug candidates in this class are fungicidal against some yeasts. Echinocandins have displayed activity against Candida biofilms in synergistic activity with amphotericin B and additive activity with fluconazole. Echinocandins are fungistatic against some molds, modestly or minimally active against dimorphic fungi; these have some activity against the spores of the fungus Pneumocystis jirovecii known as Pneumocystis carinii.
Caspofungin is used in the treatment of febrile neutropenia and as salvage therapy for the treatment of invasive aspergillosis. Micafungin is used as prophylaxis against Candida infections in hematopoietic stem cell transplantation patients. All three agents are well tolerated, with the most common adverse effects being fever, rash and phlebitis at the infusion site, they can cause a histamine-like reaction when infused too rapidly. Toxicity is uncommon, its use has been associated with alkaline phosphatase levels. The present-day clinically used echinocandins are semisynthetic pneumocandins, which are chemically lipopeptide in nature, consisting of large cyclic peptoid. Caspofungin and anidulafungin are similar cyclic hexapeptide antibiotics linked to long modified N-linked acyle fatty acid chains; the chains act. Due to their limited oral bioavailability, echinocandins are administered through intravenous infusion. Echinocandins noncompetitively inhibit beta-1,3-D-glucan synthase enzyme complex in susceptible fungi to disturb fungal cell glucan synthesis.
Beta-glucan destruction prevents resistance against osmotic forces. They have fungistatic activity against Aspergillus species, and fungicidal activity against most Candida spp. including strains that are fluconazole-resistant. In vitro and mouse models show echinocandins may enhance host immune responses by exposing antigenic beta-glucan epitopes that can accelerate host cellular recognition and inflammatory responses. Echinocandin resistance is rare. However, case studies have shown some resistance in C. albicans, C. glabrata, C. lusitaniae, C. tropicalis, C. parapsilosis. Resistance patterns include alterations in the glucan synthase, overexpression of efflux pumps, strengthening of cell wall by increased chitin production, upregulation of stress-response pathways. Due to the large molecular weight of echinocandins, they have poor oral bioavailability and are administered by intravenous infusion. In addition, their large structures limit penetration into cerebrospinal fluid and eyes. In plasma, echinocandins have a high affinity to serum proteins.
Echinocandins do not have primary interactions with P-glycoprotein pumps. Caspofungin has triphasic nonlinear pharmacokinetics, while micafungin and anidulafungin have linear elimination. Younger patients exhibit a faster rate of elimination of caspofungin. Caspofungin has some interference with ciclosporin metabolism, micafungin has some interference with sirolimus, but anidulafungin needs no dose adjustments when given with ciclosporin, tacrolimus, or voriconazole. Advantages of echinocandins: broad range, thus can be given empirically in febrile neutropenia and stem cell transplant can be used in case of azole-resistant Candida or use as a second-line agent for refractory aspergillosis long half-life low toxicity: only histamine release, fever and vomiting, phlebitis at the injection site rarely allergy and anaphylaxis not an inhibitor, inducer, or substrate of the cytochrome P450 system, or P-glycoprotein, thus minimal drug interactions lack of interference from renal failure and hemodialysis no dose adjustment is necessary based on age, race better than amphotericin B and fluconazole against yeast infections Disadvantages of echinocandins: embryotoxic in animal studies thus should be avoided if possible in pregnancy needs dose adjustment in liver disease poor ocular penetration in fungal endophthalmitis List of echinocandins: Pneumocandins Echinocandin B not clinically used, risk of hemolysis Cilofungin withdrawn from trials due to solvent toxicity Caspofungin Micafungin Anidulafungin Rezafungin CD101 IV, Rezafungin is considered to be safest echinocandins which acts longest.
It is developed by Cidara Therapeutics
Polysaccharides are polymeric carbohydrate molecules composed of long chains of monosaccharide units bound together by glycosidic linkages, on hydrolysis give the constituent monosaccharides or oligosaccharides. They range in structure from linear to branched. Examples include storage polysaccharides such as starch and glycogen, structural polysaccharides such as cellulose and chitin. Polysaccharides are quite heterogeneous, containing slight modifications of the repeating unit. Depending on the structure, these macromolecules can have distinct properties from their monosaccharide building blocks, they may be amorphous or insoluble in water. When all the monosaccharides in a polysaccharide are the same type, the polysaccharide is called a homopolysaccharide or homoglycan, but when more than one type of monosaccharide is present they are called heteropolysaccharides or heteroglycans. Natural saccharides are of simple carbohydrates called monosaccharides with general formula n where n is three or more.
Examples of monosaccharides are glucose and glyceraldehyde. Polysaccharides, have a general formula of Cxy where x is a large number between 200 and 2500; when the repeating units in the polymer backbone are six-carbon monosaccharides, as is the case, the general formula simplifies to n, where 40≤n≤3000. As a rule of thumb, polysaccharides contain more than ten monosaccharide units, whereas oligosaccharides contain three to ten monosaccharide units. Polysaccharides are an important class of biological polymers, their function in living organisms is either structure- or storage-related. Starch is used as a storage polysaccharide in plants, being found in the form of both amylose and the branched amylopectin. In animals, the structurally similar glucose polymer is the more densely branched glycogen, sometimes called "animal starch". Glycogen's properties allow it to be metabolized more which suits the active lives of moving animals. Cellulose and chitin are examples of structural polysaccharides.
Cellulose is used in the cell walls of plants and other organisms, is said to be the most abundant organic molecule on Earth. It has many uses such as a significant role in the paper and textile industries, is used as a feedstock for the production of rayon, cellulose acetate and nitrocellulose. Chitin has nitrogen-containing side branches, increasing its strength, it is found in the cell walls of some fungi. It has multiple uses, including surgical threads. Polysaccharides include callose or laminarin, xylan, mannan and galactomannan. Nutrition polysaccharides are common sources of energy. Many organisms can break down starches into glucose; these carbohydrate types can be metabolized by some protists. Ruminants and termites, for example, use microorganisms to process cellulose. Though these complex polysaccharides are not digestible, they provide important dietary elements for humans. Called dietary fiber, these carbohydrates enhance digestion among other benefits; the main action of dietary fiber is to change the nature of the contents of the gastrointestinal tract, to change how other nutrients and chemicals are absorbed.
Soluble fiber binds to bile acids in the small intestine, making them less to enter the body. Soluble fiber attenuates the absorption of sugar, reduces sugar response after eating, normalizes blood lipid levels and, once fermented in the colon, produces short-chain fatty acids as byproducts with wide-ranging physiological activities. Although insoluble fiber is associated with reduced diabetes risk, the mechanism by which this occurs is unknown. Not yet formally proposed as an essential macronutrient, dietary fiber is regarded as important for the diet, with regulatory authorities in many developed countries recommending increases in fiber intake. Starch is a glucose polymer, it is made up of a mixture of amylopectin. Amylose consists of a linear chain of several hundred glucose molecules and Amylopectin is a branched molecule made of several thousand glucose units. Starches are insoluble in water, they can be digested by breaking the alpha-linkages. Both humans and other animals have amylases, so they can digest starches.
Potato, rice and maize are major sources of starch in the human diet. The formations of starches are the ways. Glycogen serves as the secondary long-term energy storage in animal and fungal cells, with the primary energy stores being held in adipose tissue. Glycogen is made by the liver and the muscles, but can be made by glycogenesis within the brain and stomach. Glycogen is analogous to starch, a glucose polymer in plants, is sometimes referred to as animal starch, having a similar structure to amylopectin but more extensively branched and compact than starch. Glycogen is a polymer of α glycosidic bonds linked, with α-linked branches. Glycogen is found in the form of granules in the cytosol/cytoplasm in many cell types, plays an important role in the glucose cycle. Glycogen forms an energy reserve that can be mobilized to meet a sudden need for glucose, but one, less compact and more available a
A triose is a monosaccharide, or simple sugar, containing three carbon atoms. There are only three possible trioses: L-Glyceraldehyde and D-Glyceraldehyde, the two enantiomers of glyceraldehyde, which are aldotrioses because the carbonyl group is at the end of the chain, dihydroxyacetone, the only ketotriose, symmetrical and therefore has no enantiomers. Trioses are important in cellular respiration. During glycolysis, fructose-1,6-bisphosphate is broken down into glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. Lactic acid and pyruvic acid are derived from these molecules
Epoxy is either any of the basic components or the cured end products of epoxy resins, as well as a colloquial name for the epoxide functional group. Epoxy resins known as polyepoxides, are a class of reactive prepolymers and polymers which contain epoxide groups. Epoxy resins may be reacted either with themselves through catalytic homopolymerisation, or with a wide range of co-reactants including polyfunctional amines, phenols and thiols; these co-reactants are referred to as hardeners or curatives, the cross-linking reaction is referred to as curing. Reaction of polyepoxides with themselves or with polyfunctional hardeners forms a thermosetting polymer with favorable mechanical properties and high thermal and chemical resistance. Epoxy has a wide range of applications, including metal coatings, use in electronics/electrical components/LEDs, high tension electrical insulators, paint brush manufacturing, fiber-reinforced plastic materials and structural adhesives. Epoxy is sometimes used as a glue.
Epoxy resins are low molecular weight pre-polymers or higher molecular weight polymers which contain at least two epoxide groups. The epoxide group is sometimes referred to as a glycidyl or oxirane group. A wide range of epoxy resins are produced industrially; the raw materials for epoxy resin production are today petroleum derived, although some plant derived sources are now becoming commercially available. Epoxy resins are polymeric or semi-polymeric materials or an oligomer, as such exist as pure substances, since variable chain length results from the polymerisation reaction used to produce them. High purity grades can be produced for certain applications, e.g. using a distillation purification process. One downside of high purity liquid grades is their tendency to form crystalline solids due to their regular structure, which require melting to enable processing. An important criterion for epoxy resins is the epoxide group content; this is expressed as the specific amount of substance of epoxide groups in the material B under consideration, calculated as the ratio of the amount of substance of epoxide groups in this material B, n, divided by the mass m of the material B under consideration, in this case, the mass of the resin.
The SI unit for this quantity multiples thereof. Several deprecated quantities are still in use, including the so-called "epoxide number", not a number and should therefore not be referred to as such, but instead is the ratio of the amount of substance of epoxide groups, n, the mass m of the material B, with the SI unit "mol/kg"; the inverse of the epoxide number is called the "epoxide equivalent weight", the ratio of the mass of a sample B of the resin and the amount of substance of epoxide groups present in that sample B, with the SI unit "kg/mol", is a deprecated quantity. The specific amount of substance of epoxide groups is used to calculate the mass of co-reactant to use when curing epoxy resins. Epoxies are cured with stoichiometric or near-stoichiometric quantities of curative to achieve maximum physical properties; as with other classes of thermoset polymer materials, blending different grades of epoxy resin, as well as use of additives, plasticizers or fillers is common to achieve the desired processing or final properties, or to reduce cost.
Use of blending and fillers is referred to as formulating. Important epoxy resins are produced from combining epichlorohydrin and bisphenol A to give bisphenol A diglycidyl ethers. Increasing the ratio of bisphenol A to epichlorohydrin during manufacture produces higher molecular weight linear polyethers with glycidyl end groups, which are semi-solid to hard crystalline materials at room temperature depending on the molecular weight achieved; this route of synthesis is known as the "taffy" process. More modern manufacturing methods of higher molecular weight epoxy resins is to start with liquid epoxy resin and add a calculated amount of bisphenol A and a catalyst is added and the reaction heated to circa 160 °C; this process is known as "advancement". There are numerous patents and articles on this process, popular for over 20 years; as the molecular weight of the resin increases, the epoxide content reduces and the material behaves more and more like a thermoplastic. High molecular weight polycondensates form a class known as phenoxy resins and contain no epoxide groups.
These resins do however contain hydroxyl groups throughout the backbone, which may undergo other cross-linking reactions, e.g. with aminoplasts and isocyanates. Bisphenol F may undergo epoxy resin formation in a similar fashion to bisphenol A; these resins have lower viscosity and a higher mean epoxy content per gramme than bisphenol A resins, which gives them increased chemical resistance. Reaction of phenols with formaldehyde and subsequent glycidylation with epichlorohydrin produces epoxidised novolacs, such as epoxy phenol novolacs and epoxy cresol novolacs; these are viscous to solid resins with typical mean epoxide functionality of around 2 to 6. The high epoxide functionality of these resins forms a crosslinked polymer network displaying high temperature and chemical resistance, but low flexibility. A related class is cycloaliphatic epoxy resin, which contains one or more cycloaliphatic rings in the molecule (e.g. 3,4-epoxycyclohexylmethyl-3,4-epoxycyc
A furanose is a collective term for carbohydrates that have a chemical structure that includes a five-membered ring system consisting of four carbon atoms and one oxygen atom. The name derives from its similarity to the oxygen heterocycle furan, but the furanose ring does not have double bonds; the furanose ring is a cyclic hemiketal of a ketohexose. A furanose ring structure consists of four carbon and one oxygen atom with the anomeric carbon to the right of the oxygen; the highest numbered chiral carbon determines whether or not the structure has a d-configuration or L-configuration. In an l-configuration furanose, the substituent on the highest numbered chiral carbon is pointed downwards out of the plane, in a D-configuration furanose, the highest numbered chiral carbon is facing upwards; the furanose ring will have either alpha or beta configuration, depending on which direction the anomeric hydroxy group is pointing. In a d-configuration furanose, alpha configuration has the hydroxy pointing down, beta has the hydroxy pointing up.
It is the opposite in an l-configuration furanose. The anomeric carbon undergoes mutarotation in solution, the result is an equilibrium mixture of alpha-beta configurations. Pyranose
Amylopectin is a water-soluble polysaccharide and branched polymer of α-glucose units found in plants. It is one of the two components of the other being amylose. Glucose units are linked in a linear way with α glycosidic bonds. Branching takes place with α bonds occurring every 24 to 30 glucose units, resulting in a soluble molecule that can be degraded as it has many end points onto which enzymes can attach. In contrast, amylose contains few α bonds, or none at all; this causes amylose to be hydrolyzed more but have higher density and be insoluble. Its counterpart in animals is glycogen, which has the same composition and structure, but with more extensive branching that occurs every eight to 12 glucose units. Plants store starch within specialized organelles called amyloplasts; when energy is needed for cell work, the plant hydrolyzes the starch, releasing the glucose subunits. Humans and other animals that eat plant foods use amylase, an enzyme that assists in breaking down amylopectin. Starch is made of about 70 % amylopectin by weight.
Amylopectin is branched, being formed of 2,000 to 200,000 glucose units. Its inner chains are formed of 20-24 glucose subunits. Dissolved amylopectin starch has a lower tendency of retrogradation during cooling. For this main reason, the waxy starches are used in different applications as a thickening agent or stabilizer. Glycogenosis type IV Amflora, a genetically modified potato high in amylopectin with a high glycemic index Waxy corn, a Chinese maize with all amylopectin and trace amounts of amylose, different from normal corn whose endosperm contains 25% amylose International Starch Institute
Pleurotus ostreatus, the pearl oyster mushroom or tree oyster mushroom, is a common edible mushroom. It was first cultivated in Germany as a subsistence measure during World War I and is now grown commercially around the world for food, it is related to the cultivated king oyster mushroom. Oyster mushrooms can be used industrially for mycoremediation purposes; the oyster mushroom is one of the more sought wild mushrooms, though it can be cultivated on straw and other media. It has the bittersweet aroma of benzaldehyde. Both the Latin and common names refer to the shape of the fruiting body; the Latin pleurotus refers to the sideways growth of the stem with respect to the cap, while the Latin ostreatus refers to the shape of the cap which resembles the bivalve of the same name. Many believe that the name is fitting due to a flavor resemblance to oysters; the name oyster mushroom is applied to other Pleurotus species, so P. ostreatus is sometimes referred to as the tree oyster mushroom or the grey oyster mushroom to differentiate it from other species in the genus.
The mushroom has a broad, fan or oyster-shaped cap spanning 5–25 cm. The flesh is white and varies in thickness due to stipe arrangement; the gills of the mushroom are white to cream, descend on the stalk if present. If so, the stipe is off-center with a lateral attachment to wood; the spore print of the mushroom is white to lilac-gray, best viewed on dark background. The mushroom's stipe is absent; when present, it is thick. Omphalotus nidiformis is a toxic lookalike found in Japan. In North America, Omphalotus olivascens, the western jack-o'-lantern mushroom and Clitocybe dealbata, the ivory funnel mushroom, both bear a resemblance to Pleurotus ostreatus. Both Omphalotus olivascens and Clitocybe dealbata are toxic; the oyster mushroom is widespread in many temperate and subtropical forests throughout the world, although it is absent from the Pacific Northwest of North America, being replaced by P. pulmonarius and P. populinus. It is a saprotroph that acts as a primary decomposer of wood deciduous trees, beech trees in particular.
It is a white-rot wood-decay fungus. The oyster mushroom is one of the few known carnivorous mushrooms, its mycelia can kill and digest nematodes, believed to be a way in which the mushroom obtains nitrogen. The standard oyster mushroom can grow in many places, but some other related species, such as the branched oyster mushroom, grow only on trees, they may be found all year round in the UK. While this mushroom is seen growing on dying hardwood trees, it only appears to be acting saprophytically, rather than parasitically; as the tree dies of other causes, P. ostreatus grows on the increasing mass of dead and dying wood. They benefit the forest by decomposing the dead wood, returning vital elements and minerals to the ecosystem in a form usable to other plants and organisms. Despite this, the belief that P. ostreatus could damage New Zealand's forestry industry has led New Zealand to ban its importation. The oyster mushroom is used in Japanese and Chinese cookery as a delicacy, it is served on its own, in soups, stuffed, or in stir-fry recipes with soy sauce.
Oyster mushrooms are sometimes made into a sauce, used in Asian cooking, similar to oyster sauce. The mushroom's taste has been described as mild with a slight odor similar to anise; the oyster mushroom is best. Oyster mushrooms are cultivated and used in Kerala, India where a wide variety of dishes are prepared from them. Oyster mushrooms are cultivated in large clear polyethylene bags with buns of hay layered in the bags, spawn sown between the layers. Oyster mushrooms are used in the Czech and Slovak contemporary cuisine in soups and stews in a similar fashion to meat. Oyster mushrooms contain small amounts of arabitol, a sugar alcohol, which may cause gastrointestinal upset in some people; the pearl oyster mushroom is used to create mycelium bricks, mycelium furniture, leather-like products... List of Pleurotus species BooksLincoff, G. H.. National Audubon Society Field Guide to North American Mushrooms. Knopf. ISBN 978-0-394-51992-0 Spahr, D. L.. Edible and Medicinal Mushrooms of New England and Eastern Canada.
North Atlantic Books. ISBN 978-1-55643-795-3 Stamets, P.. Growing Gourmet and Medicinal Mushrooms. Ten Speed Press. ISBN 978-1-58008-175-7 Video footage of Pleurotus ostreatus Mushroom-Collecting.com – Oyster mushrooms