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By: Randolph E. Regal, BS, PharmD
- Clinical Associate Professor, Department of Clinical Pharmacy, College of Pharmacy, University of Michigan
- Clinical Pharmacist, University of Michigan Health System, Ann Arbor, Michigan
https://pharmacy.umich.edu/people/reregal
This is in contrast to gastritis gluten buy motilium with paypal the situa tion in those with cognitive impairment in general gastritis leaky gut discount 10 mg motilium visa, whereby increases in psychiatric problems are found with increasing age [40] gastritis diet questions buy motilium 10mg free shipping. The main manifestations include acquired microcephaly gastritis symptoms sore throat best order for motilium, loss of purposeful hand movements, and loss of communication and motor skills. However, adaptive behavior skills are slightly higher, with communication at a mean of 11 months, daily liv ing skills at a mean of 14 months, and socialization at a mean of 10 months. These behaviors have been assigned to various domains, with these domains (and examples) includ ing general mood (screaming spells, inconsolable crying, abrupt mood swings, and unexplained irritability); breathing problems (breath holding, swallowing air); hand behaviors (lack of purposeful grasp, difficulty stopping repetitive hand move ments); repetitive facial movements (grimacing, tongue movements); body rocking and expressionless face; nighttime behaviors (spells of screaming or laughter during the night); fear/anxiety (apparent panic, holding parts of the body rigidly); walk ing, standing (walks with a stiff-legged gait, leans on objects when standing); other (appears isolated, hand wounds from repetitive hand movements). A recent study has shown differences in the behav ioral phenotype based on the genotype. For example, those with the R294X mutation were more likely to have mood difficulties, body rocking, and nighttime behaviors, and less likely to have hand behaviors or repetitive facial movements. Conversely, those with the T158M mutation were less likely to have mood disturbances and were more likely to have hand behaviors [43]. The cardinal manifestations include both physical and behavioral characteristics, with the physical manifes tations including midface hypoplasia, upslanting palpebral fissures, broad nasal bridge, and tented upper lip with a prominent philtrum. However, in this group of 11 children, two fell within the lower limits of normal (85–115). Both receptive and expressive language were delayed, with expressive more delayed than receptive. Gross motor milestones were mildly to moderately delayed, for exam ple, independent walking was achieved at approximately 20 months. Overall, the Vineland Adaptive Behavior Scales score was in the mildly delayed range (average score 76. However, one of the domains, the socialization score, was within the normal range, whereas the other three (daily living, communication, and motor skills) were depressed. In this small sample of 11 young children, none were found to have evidence of autistic behavior. In both groups, areas of strength were long-term memory, computational skills, and perceptual skills, whereas areas of weakness were visuomotor coordination, sequencing, and response speed. In terms of adaptive behavior, the domains of daily living skills and motor skills were relative weaknesses, whereas the domains of communication and socialization were relative strengths [46]. This correlates with the finding that among adults, dependence on caretakers was greater than would be expected by the cognitive level, and it was suggested that the behavioral disturbances in these individuals affected their ability to develop independence skills [45]. The behavioral disturbances include impulsivity, aggression, tantrums, attention seeking, sleep disturbances, stereotypies, and self-injurious behavior. The stereotypies include the so-called spasmodic upper body squeeze, which is a form of self-hugging when the individual is happy or excited. Repetitive questioning has also been noted, as has a preference for adult contact [49]. The face is said to be mildly dysmorphic and includes tall, prominent forehead, downslanting palpebral fissures, and prominent jaw (more apparent with age). Cognitive abilities can range between normal cognitive achievement and moderate cognitive impair ment. Language impairments are not uncommon, and numeracy impair ment is also reported to be common. Cognitive impairment has been known to be a component manifestation for a long time; more recently, however, the behavioral aspects of this condition have been elucidated. The impairment, when present, is generally apparent by 1 year of age, with no evidence of “catch-up” by 30 months of age. Social and communication deficits, as well as motor deficits, have also been noted in some individuals with normal cognitive function. Toriello behaviors are more common in childhood and adolescence, whereas adults show more anxiety and depressed symptoms, alcoholism, and obsessive–compulsive dis orders [51, 53]. Individuals with cognitive impairment are also more likely to exhibit autism spectrum disorders or disruptive behaviors. Turner Syndrome Turner syndrome is a chromosomal condition in which a female is missing all or part of one of her X chromosomes. However, in some individuals, a deletion of part of one of the Xs can be sufficient to cause the Turner syndrome phenotype. In general, females with Turner syndrome have short stature, coarctation of the aorta, a spe cific cognitive profile, and an increased risk of impaired psychosocial skills. Rovet [56] has reviewed neurocognitive deficits in Turner syndrome in relationship to neu ronal and hormonal infiuences. These deficits (and examples of effects) include spatial ability (puzzle assembly, directional sense); visualization (visual imagery, part–whole perception); visuomotor (design copying, visual sequencing); memory (visual memory, short-term recall); attention (inhibitory control, auditory atten tion); executive function (planning, fiuent production); and language (verbal fiuency, articulation). However, not all aspects of memory, attention, executive function, or language are affected, with spared areas including verbal and rote memory; sus tained attention and focusing; set shifting; and expressive and receptive language, respectively. Overall, females with Turner syndrome are two to fourfold more likely than non-Turner females to have some sort of cognitive difficulty. Females with Turner syndrome are also more likely to have various psychological problems, although the incidence of severe psychopathology is not significantly ele vated. Among psychological problems that have been identified, social relationships seem to be the area that is most consistently identified as a problem area. Cardinal manifestations include effects on the face (narrow palpebral fissures, long, wide nose, small chin), palate (velopharyngeal insufficiency, cleft or highly arched palate) and heart (congenital cardiac defects, particularly those that are considered conotruncal). Mild cognitive impairment is an extremely common manifestation of this condition, as are some characteristic behavioral manifestations. In general, evidence for a nonverbal learning disability was found in these children. Kiley-Brabeck and Sobin [61] also found greater executive dysfunction in these children and correlated this deficit to poor social skills. Specific deficits in the areas of cooperation, assertion, and responsibility were found, whereas self-control skills did not differ from those of their control siblings. In addition, a few adults had other psychiatric diagnoses, including depression, anxiety disorder, or psychotic symptoms, as evidenced by delusions or hallucinations. Williams Syndrome Williams syndrome is a genetic condition caused by deletion of a small segment of the long arm of chromosome seven, in the region designated as 7q11. Individuals with Williams syndrome have a characteristic facial appearance (including peri orbital puffiness, full cheeks and lips, wide mouth with widely spaced teeth, and a long smooth philtrum), supravalvular aortic stenosis, transient hypercalcemia, and short stature. However, by school age, language is relatively preserved in relation to gen eral intelligence, although exceptional linguistic ability is not thought to occur [65]; indeed, within this category, pragmatic abilities are more limited than expected for the child’s developmental level. Among those that did participate, levels of anxiety or fears were lower than those in the comparison groups of children with Prader–Willi syndrome and Down syndrome. Conclusions Many, if not most, syndromes have complex phenotypes that include physical fea tures, cognitive deficits, and/or behavioral manifestations. In order to maximize the potential in any child with a syndrome, medical, educational, and behavioral needs must all be met. In addition, scientists can learn by studying these syndromes and their cognitive and behavioral phenotypes to better understand how the brain functions. Childhood developmental disorders: an academic and clinical convergence point for psychiatry, neurology, psychology and pediatrics. Studies of age-correlated features of cognitive-behavioral development in children and adolescents with genetic disorders. Cognitive deficits and associated neurological complications in individ uals with Down’s syndrome. Praxis skills in young children with Down syn drome, other developmental disabilities, and typically developing children. The relationship between acquired impairments of executive function and behavior change in adults with Down syndrome. The emerging frag ile X permutation phenotype: evidence from the domain of social cognition. Gene, brain, and behavior relationships in fragile X syndrome: evidence from neuroimaging studies. Brief report: aggression and stereotypic behavior in males with fragile X syndrome – moderating secondary genes in a “single gene” disorder. A neuropsycho logical investigation of male premutations carriers of fragile X syndrome.
The dosage is adjusted according to gastritis diet using frozen motilium 10 mg low price the disease gastritis diet ø?ëýã buy discount motilium online, the clinical picture and the stage of the illness: in fever and to gastritis diet juice buy generic motilium on-line cut the disease short gastritis diet for buy discount motilium 10mg on-line, at the start of therapy 1 tablet every 15 minutes for 2-3 hours, after which, transition to 1 tablet 3 times daily. The intradermal neural application of Gripp-Heel is particularly indicated for pains in the joints. Pharmacological and clinical notes Apis mellifica (honey bee) Oedema: ovaritis, right; hypersensitivity, nervousness. Lilium tigrinum (tiger lily) Fluor albus, dysmenorrhoea, uterus descensus, nervous cardiac disturbances, colpitis. Helonias dioica (stud flower) Conditions of exhaustion, uterus descensus et prolapsus, endometritis, remedy for women’s ailments. Platinum metallicum (platinum) Increasing and decreasing pains, mental changes, menorrhagia, myomatous haemorrhages, pruritus vulvae. Naja naja (spectacled snake) For affections of the ovaries, pain extending to the heart. Based on the individual homoeopathic constituents of Gynacoheel, therapeutic possibilities result for the treatment of inflammatory processes (reaction phases) and functional diseases of the female germinal tissue (germinoderm); ovaritis, salpingitis, para-, myo-, endometritis, colpitis, possibly in combination with Metro-Adnex-Injeel, Hormeel S and Traumeel S, possibly Arnica-Heel and Apis Homaccord; fluor albus (combination with Lamioflur, Hormeel S and Traumeel S, possibly Klimakt-Heel); kraurosis vulvae (in combination with Mercurius-Heel S, Hormeel S, Mezereum Homaccord, etc. Female sterility (combination with Hormeel S and Apis Homaccord, possibly also Arnica-Heel and Agnus castus-Injeel). As adjuvant experimentally for myomas (in addition: Aurum jodatum-Injeel forte, Hydrastis-Injeel forte and Metro-Adnex-Injeel, possibly also Sulfur-Injeel forte S as mixed injection i. As auxiliary remedy likewise to be tried for alopecia and rosacea (in association with Hormeel S, Cruroheel S and Traumeel S), as well as for habitual abortion and for frigidity. Gynacoheel, due to its composition, acts not only in checking inflammation but also exerts a function-regulating influence on the whole female genital sphere, in which case it is combined, according to the indications, with other biotherapeutic agents, several preparations being administered in 1-2-4-hourly alternation or simultaneously. The dosage is adjusted according to the disease, the clinical picture and the stage of the illness: 10 drops 3 times daily before meals. In painful conditions or acute inflammation, initially massive initial-dose therapy of 10 drops every 15 minutes, for 2-3 hours. An important auxiliary remedy for conditions of gynecological inflammation and functional disorders is Metro-Adnex-Injeel. If no result is seen, Apis Homaccord should be exchanged for Arnica-Heel, as well as Ovarium suis-Injeel and Placenta suis-Injeel mixed or alternating once to twice weekly for therapy-resistant functional disorders, in addition. Carduus marianus (milk thistle) Remedy for disorders of the hepatic functions, varicose syndrome. Based on the individual homoeopathic constituents of Hamamelis-Homaccord, therapeutic possibilities result for the treatment of venous stasis, varicose syndrome, crural ulcers, sural spasms (in addition to Spascupreel and Veratrum-Homaccord), sensation of heaviness in the legs, intermittent claudication (in addition to Arteria-Heel and Circulo-Injeel), phlebitis, thrombophlebitis (in addition to Belladonna-Homaccord and possibly Traumeel S, Cruroheel S), oedema of the legs (with Apis Homaccord). Erythema exsudativum multiforme et nodosum (in addition to Abropernol, Cruroheel S, Traumeel S tablets and possibly Osteoheel S); is often needed in addition to Cinnamomum-Homaccord N for haemorrhages. It has an absorbing action in cases of haematomas, ecchymosis, haemarthrosis (in addition to Traumeel S) orally and intradermal Iocally. The dosage is adjusted according to the disease, the symptoms and the stage of the illness: 10 drops 3-4 times daily. In conditions of pain (leg) or thrombophlebitis, firstly an aggregate dosage of 10 drops every 15-30 minutes. Method of application: In general, spread over the affected parts of the skin once to twice daily. Pharmacological and clinical notes Hamamelis virginiana (witch-hazel) Venous stasis, varicose veins, (thrombo-)phlebitis, crural ulcers, haemorrhoids, venous haemorrhages. Indications: Stimulation of the detoxicating function of the liver in acute and chronic diseases of the liver/gall. Pharmacological and clinical notes Cyanocobalaminum (Vitamin B12) Damage to the liver parenchyma, disturbance of the detoxicating hepatic function, disturbance of the fat and carbohydrate metabolism. Thymus suis (thymus gland) Stimulation of the lymphatic system, neoplasm phases, disturbances to growth and development. Colon suis (large intestine) Stimulates the detoxicating and secretory processes, intestinal stasis, intestinal tenesmus, colitis mucosa et ulcerosa. China (Peruvian bark) Remedy for debility, flatulent colic, biliary colic, enlargement of liver, gastroduodenitis. Lycopodium clavatum (club-moss) Diseases of the hepatic and cystic ducts, loss of appetite or Iycorexia, meteorism, pale yellowish complexion. Chelidonium majus (celandine) Cholelithiasis, cholecystitis, cholangitis, biliary colic, pain under the right shoulder blade, hepatopathy. Carduus marianus (milk thistle) Liver damage, congestion of the portal vein, biliary colic, haemorrhoids. Histaminum (histamine) To support the detoxicating function, increased glandular secretion, eczema and dermatosis. Natrium diethyloxalaceticum (sodium oxalacetate) Active factor of the citric acid cycle and of redox systems; intolerance to fats and albumin. Acidum alpha-ketoglutaricum (a-ketoglutaric acid) Active factor of the citric acid cycle and of redox systems; feeling of weakness. Acidum fumaricum (fumaric acid) Active factor of the citric acid cycle and of redox systems; conditions of exhaustion. Cholesterinum (cholesterol) Cholelithiasis, cirrhosis of the liver, cancer of the liver. Calcium carbonicum Hahnemanni (inner white part of the oyster shell) Conditions of exhaustion, pain in the epigastrium upon contact, persistent flatulence, biliary colic. Cynara scolymus (globe artichoke) Stimulation of the detoxicating hepatic function and of diuresis; tonic. Veratrum album (white hellebore) Affections starting feverishly, chronic vomiting, diarrhoea, conditions of collapse. Based on the individual homoeopathic constituents of Hepar compositum, therapeutical possibilities result for the stimulation of the detoxicating hepatic function in acute and chronic effectations of the liver and gall bladder. The active substances combined in Hepar compositum, such as Vitamin B12, organ extracts and homoeopathic medicaments particularly aimed at the hepatic functions, complement themselves synergistically with potentiated action. The action of Hepar compositum can be increased by the intermediate administration of Ubichinon compositum ampoules, Coenzyme compositum ampoules and possibly Thyreoidea compositum (antineoplastic action). If the disorders are located more in the left side of the epigastrium or alternate from side to side, intermediate injections of Momordica compositum, Ceanothus Homaccord, possibly also Leptandra compositum, and if there is a suspicion of neoplasia, also Podophyllum compositum as well as Viscum compositum (medium, forte), etc. Alternating injections with Hepeel, Injeel-Chol and possibly Chelidonium-Homaccord exert a favourable action; for suitable symptoms, possibly also with Nux vomica Homaccord. The latter preparations should also be administered, according to the symptoms in each case, orally with Chelidonium-Homaccord. Alternating remedies for intestinal stasis are Leptandra compositum, Momordica compositum, Nux vomica-Homaccord and Papaver-Injeel forte, and possibly also Dioscorea-Injeel forte. The dosage is adjusted according to the disease, the clinical picture and the stage of the illness: initially 1 ampoule s. Indications: Primary and secondary functional disorders of the liver; damaged liver. Dosage: Tablets: In general, 1 tablet to be dissolved under the tongue 3 times daily. Pharmacological and clinical notes Lycopodium clavatum (club-moss) Diseases of the gall bladder, hepatic and bile duct, for loss of appetite or Iycorexia and a feeling of satiation after eating very little, meteorism, sallow complexion. Chelidonium majus (celandine) Biliary colic, liver diseases, pain under the right shoulder blade, a bitter taste in the mouth. China (Peruvian bark) Loss of appetite, emaciation, meteorism, enlargement of the liver. Phosphorus (phosphorus) Remedy for affections of the parenchyma, damage to the liver parenchyma. Veratrum album (white hellebore) Feverish affections, gastro-enteritis, chronic vomiting. Citrullus colocynthis (bitter-apple) Stabbing pains, colic (patient writhing with pain). Based on the individual homoeopathic constituents of Hepeel, therapeutic possibilities result for the treatment of disturbances of the hepatic functions of the primary and secondary kind, liver damage, conditions of cholangitic and cholecystic irritation, meteorism, loss of appetite, numerous other illnesses (eczema, polyarthritis, etc. Hepeel should be interposed occasionally, with advantage, in all cellular phases; additional remedy for acne vulgaris. The dosage is adjusted according to the disease, the symptoms and the stage of the illness: for hepatic prophylaxis 1 tablet 3 times daily, possibly in association with 1 ampoule 1-3 times weekly i. For painful conditions and/or meteoristic symptoms, massive initial-dose therapy with 1-2 ampoules daily parenterally, and perorally 1 tablet to be taken every 15 minutes, repeated on several occasions. Combination treatment with Chelidonium-Homaccord and Injeel-Chol in cases of cholecystitis, cholangitis and other diseases of the biliary duct with damage to the liver parenchyma (cholostasis); with Nux vomica-Homaccord or Gastricumeel for gastritis and gastro-cardiac syndrome, and with Ceanothus-Homaccord in pancreopathy, as well as with Hepar suis-Injeel, often meets with especially great therapeutical success. Homaccords these remedies represent a series of 30 preparations which are available in packs of 30 and 100 ml of liquid for peroral medication, as well as in packs of 5, 10, 50 and 100 ampoules (of 1.
As used herein gastritis diet òâèòòåð purchase motilium 10 mg, the term "alkynylene" gastritis natural treatment motilium 10 mg without a prescription, employed alone or in combination with other terms gastritis diet ø?ëýã buy 10 mg motilium with amex, refers to gastritis diet 1500 motilium 10mg without a prescription a divalent alkynyl linking group, which can be branched or straight-chain, where the two substituents may be attached any position of the alkynylene linking group. A s used herein, the term "Ci 3 alkoxy", employed alone or in combination with other terms, refers to a group of formula -O-alkyl, wherein the alkyl group has 1to 3 carbons. A s used herein, the term "di (Ci 3-alkyl)amino" refers to a group of formula -N(alkyl) 2, wherein the two alkyl groups each has, independently, 1to 3 carbon atoms. A s used herein, the term "Ci 4 alkoxycarbonyl" refers to a group of formula -C(0)0 alkyl, wherein the alkyl group has 1to 4 carbon atoms. A s used herein, the term "Ci 3alkylcarbonyl" refers to a group of formula -C(0)-alkyl, wherein the alkyl group has 1to 3 carbon atoms. A s used herein, the term "Ci alkylthio" refers to a group of formula -S-(Ci alkyl). A s used herein, the term "Ci alkylsulfonyl" refers to a group of formula -S(0) 2-alkyl, 3 wherein the alkyl group has 1to 3 carbon atoms. As used herein, the term "di(Ci 3-alkyl)carbamyl" refers to a group of formula C(0)N(alkyl) 2, wherein the two alkyl groups each has, independently, 1 to 3 carbon atoms. As used herein, the term "di(Ci 3 alkyl)aminosulfonyl" refers to a group of formula S(0) 2N(alkyl) 2, wherein each alkyl independently has 1 to 3 carbon atoms. As used herein, the term "C0 p alkoxy-C m-alkyl" refers to a group of formula -alkylene O-alkyl, wherein said alkylene group has n to m carbon atoms and said alkyl group has o to p carbon atoms. In some embodiments, the alkyl and alkylene groups each independently have 1 to 3 carbon atoms. As used herein, the term "carbonyl", employed alone or in combination with other terms, refers to a -C(O) group. As used herein, "halo" or "halogen", employed alone or in combination with other terms, includes fluoro, chloro, bromo, and iodo. As used herein, the term "C m haloalkyl", employed alone or in combination with other terms, refers to an C m alkyl group having up to {2(n to m)+l } halogen atoms which may either be the same or different. As used herein, "C mhaloalkoxy" refers to a group of formula -O-haloalkyl having n to m carbon atoms. As used herein, the term "cyano-C m alkyl" refers to a C m alkyl substituted by a cyano group. As used herein, the appearance of the term "monocyclic" before the name of a moiety indicates that the moiety has a single ring. As used herein, the term "cycloalkyl", employed alone or in combination with other terms, refers to a non-aromatic cyclic hydrocarbon moiety, which may optionally contain one or more alkenylene groups as part of the ring structure. Also included in the definition of cycloalkyl are moieties that have one or more aromatic rings fused. One or more ring-forming carbon atoms of a cycloalkyl group can be oxidized to form carbonyl linkages. In some embodiments, cycloalkyl is a 3-10 membered cycloalkyl, which is monocyclic or bicyclic. Examplary cycloalkyl groups include 1,2,3,4-tetrahydro-naphthalene, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptatrienyl, norbornyl, norpinyl, norcarnyl, adamantyl, and the like. In some embodiments, the cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. As used herein, the term "aryl", employed alone or in combination with other terms, refers to a monocyclic or polycyclic. In some embodiments, aryl is Ce-io a y n some embodiments, the aryl group is a naphthalene ring or phenyl ring. As used herein, the term "heteroaryl", employed alone or in combination with other terms, refers to a monocyclic or polycyclic. In some embodiments, heteroaryl is a 5-10 membered heteroaryl, which is monocyclic or bicyclic, comprising 1 to 9 carbon atoms and 1, 2, 3, or 4 heteroatom ring members independently selected from nitrogen, sulfur and oxygen. In some embodiments, heteroaryl is a 5-6 membered heteroaryl, which is monocyclic or bicyclic, comprising 1 to 5 carbon atoms and 1, 2, 3, or 4 heteroatom ring members independently selected from nitrogen, sulfur, and oxygen. When the heteroaryl group contains more than one heteroatom ring member, the heteroatoms may be the same or different. Example heteroaryl groups include, but are not limited to, pyridine, pyrimidine, pyrazine, pyridazine, pyrrole, pyrazole, azolyl, oxazole, thiazole, imidazole, furan, thiophene, quinoline, isoquinoline, indole, benzothiophene, benzofuran, benzisoxazole, imidazo[l,2-b]thiazole, purine, or the like. A five-membered ring heteroaryl is a heteroaryl with a ring having five ring atoms wherein one or more. Exemplary five-membered ring heteroaryls are thienyl, furyl, pyrrolyl, imidazolyl, thiazolyl, oxazolyl, pyrazolyl, isothiazolyl, isoxazolyl, 1,2,3-triazolyl, tetrazolyl, 1,2,3-thiadiazolyl, 1,2,3 oxadiazolyl, 1,2,4-triazolyl, 1,2,4-thiadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-triazolyl, 1,3,4 thiadiazolyl, and 1,3,4-oxadiazolyl. A six-membered ring heteroaryl is a heteroaryl with a ring having six ring atoms wherein one or more. Exemplary six-membered ring heteroaryls are pyridyl, pyrazinyl, pyrimidinyl, triazinyl and pyridazinyl. A s used herein, the term "heteroarylalkyl" refers to a group of formula -alkylene heteroaryl. In some embodiments, heteroarylalkyl is Ci ci heteroaryl-Ci 3 alkyl, wherein the heteroaryl portion is monocyclic or bicyclic and has 1, 2, 3, or 4 heteroatom ring members independently selected from nitrogen, sulfur and oxygen. A s used herein, the term "heterocycloalkyl", employed alone or in combination with other terms, refers to non-aromatic ring system, which may optionally contain one or more alkenylene or alkynylene groups as part of the ring structure, and which has at least one heteroatom ring member independently selected from nitrogen, sulfur and oxygen. When the heterocycloalkyl groups contains more than one heteroatom, the heteroatoms may be the same or different. Also included in the definition of heterocycloalkyl are moieties that have one or more aromatic rings fused. The carbon atoms or heteroatoms in the ring(s) of the heterocycloalkyl group can be oxidized to form a carbonyl, or sulfonyl group (or other oxidized linkage) or a nitrogen atom can be quaternized. In some embodiments, heterocycloalkyl is 5-10 membered heterocycloalkyl, which is monocyclic or bicyclic, comprising 2 to 9 carbon atoms and 1, 2, 3, or 4 heteroatom ring members independently selected from nitrogen, sulfur, and oxygen. Examples of heterocycloalkyl groups include 1,2,3,4 tetrahydro-quinoline, azetidine, azepane, pyrrolidine, piperidine, piperazine, morpholine, thiomorpholine, pyran, and a 2-oxo-l,3-oxazolidine ring. As used herein, the term "heterocycloalkylalkyl" refers to a group of formula -alkylene heterocycloalkyl. In some embodiments, heterocycloalkylalkyl is C 2 heterocycloalkyl-Ci 3 alkyl, wherein the heterocycloalkyl portion is monocyclic or bicyclic and has 1, 2, 3, or 4 heteroatom ring members independently selected from nitrogen, sulfur and oxygen. All stereoisomers, such as enantiomers and diastereomers, are intended unless otherwise indicated. Compounds of the present invention that contain asymmetrically substituted carbon atoms can be isolated in optically active or racemic forms. Methods on how to prepare optically active forms from optically inactive starting materials are known in the art, such as by resolution of racemic mixtures or by stereoselective synthesis. Many geometric isomers of olefins, C=N double bonds, and the like can also be present in the compounds described herein, and all such stable isomers are contemplated in the present invention. Cis and trans geometric isomers of the compounds of the present invention are described and may be isolated as a mixture of isomers or as separated isomeric forms. Resolution of racemic mixtures of compounds can be carried out by any of numerous methods known in the art. An example method includes fractional recrystallizaion using a chiral resolving acid which is an optically active, salt-forming organic acid. Suitable resolving agents for fractional recrystallization methods are, for example, optically active acids, such as the D and L forms of tartaric acid, diacetyltartaric acid, dibenzoyltartaric acid, mandelic acid, malic acid, lactic acid or the various optically active camphorsulfonic acids such as fi-camphorsulfonic acid. Other resolving agents suitable for fractional crystallization methods include stereoisomerically pure forms of a-methylbenzylamine. Resolution of racemic mixtures can also be carried out by elution on a column packed with an optically active resolving agent. Tautomeric forms result from the swapping of a single bond with an adjacent double bond together with the concomitant migration of a proton. Tautomeric forms include prototropic tautomers which are isomeric protonation states having the same empirical formula and total charge. Example prototropic tautomers include ketone enol pairs, amide imidic acid pairs, lactam lactim pairs, enamine imine pairs, and annular forms where a proton can occupy two or more positions of a heterocyclic system, for example, 1H and 3H-imidazole, 1H-, 2H and 4H 1,2,4-triazole, 1H and 2H isoindole, and 1H and 2H-pyrazole. Tautomeric forms can be in equilibrium or sterically locked into one form by appropriate substitution. Compounds of the invention can also include all isotopes of atoms occurring in the intermediates or final compounds. Isotopes include those atoms having the same atomic number but different mass numbers. The term, "compound," as used herein is meant to include all stereoisomers, geometric iosomers, tautomers, and isotopes of the structures depicted.
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Diseases
- Coloboma of macula
- Chromosome 1, monosomy 1p34 p32
- Mental retardation short stature heart and skeletal anomalies
- Craniotelencephalic dysplasia
- Lymphoma, small cleaved-cell, diffuse
- Nesidioblastosis of pancreas
- Cystic hygroma