Simplified molecular-input line-entry system
The simplified molecular-input line-entry system is a specification in the form of a line notation for describing the structure of chemical species using short ASCII strings. SMILES strings can be imported by most molecule editors for conversion back into two-dimensional drawings or three-dimensional models of the molecules; the original SMILES specification was initiated in the 1980s. It has since been extended. In 2007, an open standard called. Other linear notations include the Wiswesser line notation, ROSDAL, SYBYL Line Notation; the original SMILES specification was initiated by David Weininger at the USEPA Mid-Continent Ecology Division Laboratory in Duluth in the 1980s. Acknowledged for their parts in the early development were "Gilman Veith and Rose Russo and Albert Leo and Corwin Hansch for supporting the work, Arthur Weininger and Jeremy Scofield for assistance in programming the system." The Environmental Protection Agency funded the initial project to develop SMILES. It has since been modified and extended by others, most notably by Daylight Chemical Information Systems.
In 2007, an open standard called "OpenSMILES" was developed by the Blue Obelisk open-source chemistry community. Other'linear' notations include the Wiswesser Line Notation, ROSDAL and SLN. In July 2006, the IUPAC introduced the InChI as a standard for formula representation. SMILES is considered to have the advantage of being more human-readable than InChI; the term SMILES refers to a line notation for encoding molecular structures and specific instances should be called SMILES strings. However, the term SMILES is commonly used to refer to both a single SMILES string and a number of SMILES strings; the terms "canonical" and "isomeric" can lead to some confusion when applied to SMILES. The terms are not mutually exclusive. A number of valid SMILES strings can be written for a molecule. For example, CCO, OCC and CC all specify the structure of ethanol. Algorithms have been developed to generate the same SMILES string for a given molecule; this SMILES is unique for each structure, although dependent on the canonicalization algorithm used to generate it, is termed the canonical SMILES.
These algorithms first convert the SMILES to an internal representation of the molecular structure. Various algorithms for generating canonical SMILES have been developed and include those by Daylight Chemical Information Systems, OpenEye Scientific Software, MEDIT, Chemical Computing Group, MolSoft LLC, the Chemistry Development Kit. A common application of canonical SMILES is indexing and ensuring uniqueness of molecules in a database; the original paper that described the CANGEN algorithm claimed to generate unique SMILES strings for graphs representing molecules, but the algorithm fails for a number of simple cases and cannot be considered a correct method for representing a graph canonically. There is no systematic comparison across commercial software to test if such flaws exist in those packages. SMILES notation allows the specification of configuration at tetrahedral centers, double bond geometry; these are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed isomeric SMILES.
A notable feature of these rules is. The term isomeric SMILES is applied to SMILES in which isotopes are specified. In terms of a graph-based computational procedure, SMILES is a string obtained by printing the symbol nodes encountered in a depth-first tree traversal of a chemical graph; the chemical graph is first trimmed to remove hydrogen atoms and cycles are broken to turn it into a spanning tree. Where cycles have been broken, numeric suffix labels are included to indicate the connected nodes. Parentheses are used to indicate points of branching on the tree; the resultant SMILES form depends on the choices: of the bonds chosen to break cycles, of the starting atom used for the depth-first traversal, of the order in which branches are listed when encountered. Atoms are represented by the standard abbreviation of the chemical elements, in square brackets, such as for gold. Brackets may be omitted in the common case of atoms which: are in the "organic subset" of B, C, N, O, P, S, F, Cl, Br, or I, have no formal charge, have the number of hydrogens attached implied by the SMILES valence model, are the normal isotopes, are not chiral centers.
All other elements must be enclosed in brackets, have charges and hydrogens shown explicitly. For instance, the SMILES for water may be written as either O or. Hydrogen may be written as a separate atom; when brackets are used, the symbol H is added if the atom in brackets is bonded to one or more hydrogen, followed by the number of hydrogen atoms if greater than 1 by the sign + for a positive charge or by - for a negative charge. For example, for ammonium. If there is more than one charge, it is written as digit.
The respiratory center is located in the medulla oblongata and pons, in the brainstem. The respiratory center is made up of three major respiratory groups of neurons, two in the medulla and one in the pons. In the medulla they are the dorsal respiratory group, the ventral respiratory group. In the pons, the pontine respiratory group includes two areas known as the pneumotaxic centre and the apneustic centre; the respiratory centre is responsible for generating and maintaining the rhythm of respiration, of adjusting this in homeostatic response to physiological changes. The respiratory center receives input from chemoreceptors, the cerebral cortex, the hypothalamus in order to regulate the rate and depth of breathing. Input is stimulated by altered levels of oxygen, carbon dioxide, blood pH, by hormonal changes relating to stress, anxiety from the hypothalamus, by signals from the cerebral cortex to give a conscious control of respiration. Injury to respiratory groups can cause various breathing disorders that may require mechanical ventilation, is associated with a poor prognosis.
The respiratory centre is divided into two in the medulla and one in the pons. The two groups in the medulla are the ventral respiratory group. In the pons, the pontine respiratory group is made up of two areas – the pneumotaxic centre and the apneustic centre; the dorsal and ventral medullary groups control the basic rhythm of respiration. The dorsal respiratory group has the most fundamental role in the control of respiration, initiating inspiration; the DRG is a collection of neurons forming an elongated mass that extends most of the length of the dorsal medulla. They are near to the central canal of the spinal cord, just behind the ventral group, they maintain the rate of respiration. Most of the neurons are located in the nucleus of the solitary tract. Other important neurons are found in the adjacent areas including the reticular substance of the medulla; the solitary nucleus is the end-point for sensory information arriving from the pontine respiratory group, from two cranial nerves – the vagus nerve, the glossopharyngeal nerve.
The solitary nucleus sends signals to the respiratory center from peripheral chemoreceptors and other types of receptors in the lungs in particular the stretch receptors. The dorsal respiratory group is thus seen as an integrating center that gives output to the ventral respiratory group to modify the breathing rhythm. In the medulla, the ventral respiratory group consists of four groups of neurons that make up the exhalation area of respiratory control; this area is in the ventrolateral part of medulla, about 5 mm anterior and lateral to the dorsal respiratory group. The neurons involved include those in the nucleus ambiguus, the nucleus retroambiguus, the interneurons in the pre-Bötzinger complex; the VRG contains both expiratory neurons. In quiet, restful breathing, the ventral respiratory group of neurons are inactive, they become active in forceful breathing. The VRG sends inhibitory impulses to the apneustic center. In the pontine tegmentum in the pons, the pontine respiratory group includes the pneumotaxic and apneustic centers.
These have connections between them, from both to the solitary nucleus. The pneumotaxic center is located in the upper part of the pons, its nuclei are the medial parabrachial nucleus. The pneumotaxic center controls the pattern of breathing; the pneumotaxic center is considered an antagonist to the apneustic center, cyclically inhibiting inhalation. The pneumotaxic center is responsible for providing an inspiratory off-switch, it limits the burst of action potentials in the phrenic nerve decreasing the tidal volume and regulating the respiratory rate. Absence of the center results in an increase in depth of respiration and a decrease in respiratory rate; the pneumotaxic center regulates the amount of air. The dorsal respiratory group has rhythmic bursts of activity that are constant in duration and interval; when a faster rate of breathing is needed the pneumotaxic center signals the dorsal respiratory group to speed up. When longer breaths are needed the bursts of activity are elongated. All the information that the body uses to help respiration happens in the pneumotaxic center.
If this was damaged or in any way harmed it would make breathing impossible. One study on this subject was on anesthetized paralyzed cats after bilateral vagotomy. Ventilation was monitored in awake and anesthetized cats breathing air or CO2. Ventilation was monitored both before and after lesions to the pneumotaxic center region and after subsequent bilateral vagotomy. Cats with pontine lesions had a prolonged inhalation duration. In cats, after anaesthesia and bivagotomy, pontine transection has been described as evoking a long sustained inspiratory discharges interrupted by short expiratory pauses. In rats on the other hand, after anaesthesia and pontine transection, this breathing pattern was not observed, either in vivo or in vitro; these results suggest interspecies differences between rat and cat in the pontine influences on the medullary respiratory center. The apneustic center of the lower pons appears to promote inhalation by a constant stimulation of the neurons in the medulla oblongata.
The apneustic center sends signals to the dorsal group in the medulla to delay the'switch off', the inspiratory off switch signal of the inspiratory ramp provided by the pneumotaxic centre. It controls the intensity of breathing
European Chemicals Agency
The European Chemicals Agency is an agency of the European Union which manages the technical and administrative aspects of the implementation of the European Union regulation called Registration, Evaluation and Restriction of Chemicals. ECHA is the driving force among regulatory authorities in implementing the EU's chemicals legislation. ECHA helps companies to comply with the legislation, advances the safe use of chemicals, provides information on chemicals and addresses chemicals of concern, it is located in Finland. The agency headed by Executive Director Bjorn Hansen, started working on 1 June 2007; the REACH Regulation requires companies to provide information on the hazards and safe use of chemical substances that they manufacture or import. Companies register this information with ECHA and it is freely available on their website. So far, thousands of the most hazardous and the most used substances have been registered; the information is technical but gives detail on the impact of each chemical on people and the environment.
This gives European consumers the right to ask retailers whether the goods they buy contain dangerous substances. The Classification and Packaging Regulation introduces a globally harmonised system for classifying and labelling chemicals into the EU; this worldwide system makes it easier for workers and consumers to know the effects of chemicals and how to use products safely because the labels on products are now the same throughout the world. Companies need to notify ECHA of the labelling of their chemicals. So far, ECHA has received over 5 million notifications for more than 100 000 substances; the information is available on their website. Consumers can check chemicals in the products. Biocidal products include, for example, insect disinfectants used in hospitals; the Biocidal Products Regulation ensures that there is enough information about these products so that consumers can use them safely. ECHA is responsible for implementing the regulation; the law on Prior Informed Consent sets guidelines for the import of hazardous chemicals.
Through this mechanism, countries due to receive hazardous chemicals are informed in advance and have the possibility of rejecting their import. Substances that may have serious effects on human health and the environment are identified as Substances of Very High Concern 1; these are substances which cause cancer, mutation or are toxic to reproduction as well as substances which persist in the body or the environment and do not break down. Other substances considered. Companies manufacturing or importing articles containing these substances in a concentration above 0,1% weight of the article, have legal obligations, they are required to inform users about the presence of the substance and therefore how to use it safely. Consumers have the right to ask the retailer whether these substances are present in the products they buy. Once a substance has been identified in the EU as being of high concern, it will be added to a list; this list is available on ECHA's website and shows consumers and industry which chemicals are identified as SVHCs.
Substances placed on the Candidate List can move to another list. This means that, after a given date, companies will not be allowed to place the substance on the market or to use it, unless they have been given prior authorisation to do so by ECHA. One of the main aims of this listing process is to phase out SVHCs where possible. In its 2018 substance evaluation progress report, ECHA said chemical companies failed to provide “important safety information” in nearly three quarters of cases checked that year. "The numbers show a similar picture to previous years" the report said. The agency noted that member states need to develop risk management measures to control unsafe commercial use of chemicals in 71% of the substances checked. Executive Director Bjorn Hansen called non-compliance with REACH a "worry". Industry group CEFIC acknowledged the problem; the European Environmental Bureau called for faster enforcement to minimise chemical exposure. European Chemicals Bureau Official website
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
Theobroma cacao called the cacao tree and the cocoa tree, is a small evergreen tree in the family Malvaceae, native to the deep tropical regions of the Americas. Its seeds, cocoa beans, are used to make cocoa solids, cocoa butter and chocolate. Leaves are alternate, unlobed, 10–40 cm long and 5–20 cm broad; the flowers are produced in clusters directly on older branches. The flowers are small, 1–2 cm diameter, with pink calyx; the floral formula, used to represent the structure of a flower using numbers, is ✶ K5 C5 A G. While many of the world's flowers are pollinated by bees or butterflies/moths, cacao flowers are pollinated by tiny flies, Forcipomyia midges in the subfamily Forcipomyiinae. Using the natural pollinator Forcipomyia midges for Theobroma cacao was shown to have more fruit production than using artificial pollinators; the fruit, called a cacao pod, is ovoid, 15–30 cm long and 8–10 cm wide, ripening yellow to orange, weighs about 500 g when ripe. The pod contains 20 to 60 seeds called "beans", embedded in a white pulp.
The seeds are the main ingredient of chocolate, while the pulp is used in some countries to prepare refreshing juice, smoothies and nata. Discarded until practices changed in the 21st century, the fermented pulp may be distilled into an alcoholic beverage; each seed contains a significant amount of fat as cocoa butter. The fruit's active constituent is a compound similar to caffeine. Cacao belongs to the genus Theobroma classified under the subfamily Byttnerioideae of the mallow family Malvaceae. Cacao is one of 17 species of Theobroma. In 2008, researchers proposed a new classification based upon morphological and genomic criteria: 10 groups have been named according to their geographic origin or the traditional cultivar name; these groups are: Amelonado, Nacional, Curaray, Cacao guiana, Marañon, Purús. The generic name is derived from the Greek for "food of the gods"; the specific name cacao is the Hispanization of the name of the plant in indigenous Mesoamerican languages. The cacao was known as kakaw in K'iche' and Classic Maya.
T. cacao is distributed from southeastern Mexico to the Amazon basin. There were two hypotheses about its domestication. More recent studies of patterns of DNA diversity, suggest that this is not the case. One study classified them into 10 distinct genetic clusters; this study identified areas, for example around Iquitos in modern Peru and Ecuador, where representatives of several genetic clusters originated more than 5000 years ago, leading to development of the variety, Nacional cocoa bean. This result suggests that this is where T. cacao was domesticated for the pulp that surrounds the beans, eaten as a snack and fermented into a mildly alcoholic beverage. Using the DNA sequences and comparing them with data derived from climate models and the known conditions suitable for cacao, one study refined the view of domestication, linking the area of greatest cacao genetic diversity to a bean-shaped area that encompasses Ecuador, the border between Brazil and Peru and the southern part of the Colombian-Brazilian border.
Climate models indicate that at the peak of the last ice age 21,000 years ago, when habitat suitable for cacao was at its most reduced, this area was still suitable, so provided a refugium for the species. Cacao trees grow well as understory plants in humid forest ecosystems; this is true of abandoned cultivated trees, making it difficult to distinguish wild trees from those whose parents may have been cultivated. Cultivation and cultural elaboration of cacao were early and extensive in Mesoamerica. Ceramic vessels with residues from the preparation of cacao beverages have been found at archaeological sites dating back to the Early Formative period. For example, one such vessel found at an Olmec archaeological site on the Gulf Coast of Veracruz, Mexico dates cacao's preparation by pre-Olmec peoples as early as 1750 BC. On the Pacific coast of Chiapas, Mexico, a Mokaya archaeological site provides evidence of cacao beverages dating earlier, to 1900 BC; the initial domestication was related to the making of a fermented, thus alcoholic beverage.
In 2018, researchers who analysed the genome of cultivated cacao trees concluded that the domesticated cacao trees all originated from a single domestication event that occurred about 3,600 years ago somewhere in Central America. Several mixtures of cacao are described in ancient texts, for ceremonial or medicinal, as well as culinary, purposes; some mixtures included maize, chili and honey. Archaeological evidence for use of cacao, while sparse, has come from the recovery of whole cacao beans at Uaxactun and from the preservation of wood fragments of the cacao tree at Belize sites including Cuello and Pulltrouser Swamp. In addition, analysis of residues from ceramic vessels has found traces of theobromine and caffeine in early formative vessels from Puerto Escondido, Honduras and in middle formative vessels from Colha, Belize using similar techniques to those used to extract chocolate residues from four classic period (around 400
Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to determine the fate of substances administered to a living organism. The substances of interest include any chemical xenobiotic such as: pharmaceutical drugs, food additives, etc, it attempts to analyze chemical metabolism and to discover the fate of a chemical from the moment that it is administered up to the point at which it is eliminated from the body. Pharmacokinetics is the study of how an organism affects a drug, whereas pharmacodynamics is the study of how the drug affects the organism. Both together influence dosing and adverse effects, as seen in PK/PD models. Pharmacokinetics describes how the body affects a specific xenobiotic/chemical after administration through the mechanisms of absorption and distribution, as well as the metabolic changes of the substance in the body, the effects and routes of excretion of the metabolites of the drug. Pharmacokinetic properties of chemicals are affected by the route of administration and the dose of administered drug.
These may affect the absorption rate. Models have been developed to simplify conceptualization of the many processes that take place in the interaction between an organism and a chemical substance. One of these, the multi-compartmental model, is the most used approximations to reality; the various compartments that the model is divided into are referred to as the ADME scheme: Liberation – the process of release of a drug from the pharmaceutical formulation. See IVIVC. Absorption – the process of a substance entering the blood circulation. Distribution – the dispersion or dissemination of substances throughout the fluids and tissues of the body. Metabolism – the recognition by the organism that a foreign substance is present and the irreversible transformation of parent compounds into daughter metabolites. Excretion – the removal of the substances from the body. In rare cases, some drugs irreversibly accumulate in body tissue; the two phases of metabolism and excretion can be grouped together under the title elimination.
The study of these distinct phases involves the use and manipulation of basic concepts in order to understand the process dynamics. For this reason in order to comprehend the kinetics of a drug it is necessary to have detailed knowledge of a number of factors such as: the properties of the substances that act as excipients, the characteristics of the appropriate biological membranes and the way that substances can cross them, or the characteristics of the enzyme reactions that inactivate the drug. All these concepts can be represented through mathematical formulas that have a corresponding graphical representation; the use of these models allows an understanding of the characteristics of a molecule, as well as how a particular drug will behave given information regarding some of its basic characteristics such as its acid dissociation constant and solubility, absorption capacity and distribution in the organism. The model outputs for a drug can be used in industry or in the clinical application of pharmacokinetic concepts.
Clinical pharmacokinetics provides many performance guidelines for effective and efficient use of drugs for human-health professionals and in veterinary medicine. The following are the most measured pharmacokinetic metrics: In pharmacokinetics, steady state refers to the situation where the overall intake of a drug is in dynamic equilibrium with its elimination. In practice, it is considered that steady state is reached when a time of 4 to 5 times the half-life for a drug after regular dosing is started; the following graph depicts a typical time course of drug plasma concentration and illustrates main pharmacokinetic metrics: Pharmacokinetic modelling is performed by noncompartmental or compartmental methods. Noncompartmental methods estimate the exposure to a drug by estimating the area under the curve of a concentration-time graph. Compartmental methods estimate the concentration-time graph using kinetic models. Noncompartmental methods are more versatile in that they do not assume any specific compartmental model and produce accurate results acceptable for bioequivalence studies.
The final outcome of the transformations that a drug undergoes in an organism and the rules that determine this fate depend on a number of interrelated factors. A number of functional models have been developed in order to simplify the study of pharmacokinetics; these models are based on a consideration of an organism as a number of related compartments. The simplest idea is to think of an organism as only one homogenous compartment; this monocompartmental model presupposes that blood plasma concentrations of the drug are a true reflection of the drug's concentration in other fluids or tissues and that the elimination of the drug is directly proportional to the drug's concentration in the organism. However, these models do not always reflect the real situation within an organism. For example, not all body tissues have the same blood supply, so the distribution of the drug will be slower in these tissues than in others with a better blood supply. In addition, there are some tissues (s
Theobromine known as xantheose, is a bitter alkaloid of the cacao plant, with the chemical formula C7H8N4O2. It is found in chocolate, as well as in a number of other foods, including the leaves of the tea plant, the kola nut, it is classified as others of which include theophylline and caffeine. The compounds differ. Despite its name, the compound contains no bromine—theobromine is derived from Theobroma, the name of the genus of the cacao tree with the suffix -ine given to alkaloids and other basic nitrogen-containing compounds. Theobromine is a water-soluble, bitter powder. Theobromine is white or colourless, it has an effect similar to, but lesser than, that of caffeine in the human nervous system, making it a lesser homologue. Theobromine is an isomer of theophylline, as well as paraxanthine. Theobromine is categorized as a dimethyl xanthine. Theobromine was first discovered in 1841 in cacao beans by Russian chemist Aleksandr Voskresensky. Synthesis of theobromine from xanthine was first reported in 1882 by Hermann Emil Fischer.
Theobromine is the primary alkaloid found in chocolate. Cocoa powder can vary in the amount of theobromine, from 2% theobromine, up to higher levels around 10%. Cocoa butter only contains trace amounts of theobromine. There are higher concentrations in dark than in milk chocolate. Theobromine can be found in small amounts in the kola nut, the guarana berry, yerba mate, the tea plant. 28 grams of milk chocolate contains 60 milligrams of theobromine, while the same amount of dark chocolate contains about 200 milligrams. Cocoa beans contain 1% theobromine. Plant species and components with substantial amounts of theobromine are: Theobroma cacao – seed and seed coat Theobroma bicolor – seed coat Ilex paraguariensis – leaf Camellia sinensis – leafThe mean theobromine concentrations in cocoa and carob products are: Theobromine is a purine alkaloid derived from xanthosine, a nucleoside. Cleavage of the ribose and N-methylation yields 7-methylxanthosine. 7-Methylxanthosine in turn is the precursor to theobromine, which in turn is the precursor to caffeine.
Without dietary intake, theobromine may occur in the body as it is a product of the human metabolism of caffeine, metabolised in the liver into 12% theobromine, 4% theophylline, 84% paraxanthine. In the liver, theobromine is subsequently into methyluric acid. Important enzymes include CYP1A2 and CYP2E1. Like other methylated xanthine derivatives, theobromine is both a: competitive nonselective phosphodiesterase inhibitor, which raises intracellular cAMP, activates PKA, inhibits TNF-alpha and leukotriene synthesis, reduces inflammation and innate immunity and nonselective adenosine receptor antagonist; as a phosphodiesterase inhibitor, theobromine prevents the phosphodiesterase enzymes from converting the active cAMP to an inactive form. CAMP works as a second messenger in many hormone- and neurotransmitter-controlled metabolic systems, such as the breakdown of glycogen; when the inactivation of cAMP is inhibited by a compound such as theobromine, the effects of the neurotransmitter or hormone that stimulated the production of cAMP are much longer-lived.
In general, the net result is a stimulatory effect. Theobromine is a vasodilator, a diuretic, heart stimulant, it is not used as a medicinal drug. The amount of theobromine found in chocolate is small enough that chocolate can, in general, be safely consumed by humans. At doses of 0.8–1.5 g/day, sweating and severe headaches were noted, with limited mood effects found at 250 mg/day. Theobromine and caffeine are similar in. Theobromine is weaker in both its inhibition of cyclic nucleotide phosphodiesterases and its antagonism of adenosine receptors; the potential inhibitory effect of theobromine on phosphodiesterases is seen only at amounts much higher than what people would consume in a typical diet including chocolate. Animals that metabolize theobromine more such as dogs, can succumb to theobromine poisoning from as little as 50 grams of milk chocolate for a smaller dog and 400 grams, or around nine 44-gram small milk chocolate bars, for an average-sized dog; the concentration of theobromine in dark chocolates is up to 10 times that of milk chocolate – meaning dark chocolate is far more toxic to dogs per unit weight or volume than milk chocolate.
The same risk is reported for cats as well, although cats are less to ingest sweet food, with most cats having no sweet taste receptors. Complications include digestive issues, excitability, a slow heart rate. Stages of theobromine poisoning include epileptic-like seizures and death. If caught early on, theobromine poisoning is treatable. Although not common, the effects of theobromine poisoning can be fatal. In 2014, four American black bears were found dead at a bait site in New Hampshire. A necropsy and toxicology report performed at the University of New Hampshire in 2015 confirmed they died of heart failure caused by theobromine after they consumed 41 kilograms of chocolate and doughnuts placed at the site as bait. A similar incident killed a black bear cub in Michigan in 2011; the toxicity for birds is not known, but it is assumed that it is toxic to birds. History of chocolate Theodrenaline