/A/ study in which rats were gavaged with a mixture of capsaicinoids /was reported/. These substances were extensively metabolized by a variety of metabolic pathways, including 1) hydrolysis of the acid-amide bond and deamination to form vanillylamine, 2) hydroxylation of the vanillyl ring, 3) oxidation of the hydroxyl group in the ring and 4) oxidation of the terminal carbon in the sidechain. /Capsaicinoids/
Later steps of carotenoid biosynthesis catalyzed by cyclase enzymes involve the formation of alpha, beta, and kappa-rings. Examination of the primary structure of lycopene beta-cyclase revealed 55% identity with that of antheraxanthin kappa-cyclase. Recombinant lycopene beta-cyclase afforded only beta-carotene, while recombinant antheraxanthin kappa-cyclase catalyzed the formation of beta-carotene from lycopene as well as the conversion of antheraxanthin into the kappa-carotenoid capsanthin. Since the formation of beta- and kappa-rings involves a transient carotenoid carbocation, this suggests that both cyclases initiate and/or neutralize the incipient carbocation by similar mechanisms. Several amine derivatives protonated at physiological pH were used to examine the molecular basis of this phenomenon. The beta-and kappa-cyclases displayed similar inhibition patterns. Affinity or photoaffinity labeling using p-dimethylamino-benzenediazonium fluoroborate, N,N-dimethyl-2-phenylaziridinium, and nicotine irreversibly inactivated both cyclase enzymes. Photoaffinity labeling using [H(3)]nicotine followed by radiosequence analysis and site-directed mutagenesis revealed the existence of two cyclase domains characterized by the presence of reactive aromatic and carboxylic amino acid residues. /Investigators/ propose that these residues represent the "negative point charges" involved in the coordination of the incipient carotenoid carbocations.
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
/HUMAN EXPOSURE STUDIES/ A low incidence of local reactions in dermatitis patients was observed in skin tests with paprika. Three out of 336 dermatitis patients reacted to paprika powder in a 24 hr patch test. Skin scratch tests with paprika powder were also positive in 59 out of 894 patients susceptible to allergenic agents (atopic patients), but no reactions were seen in 362 normal individual. /Paprika powder/
/CASE REPORTS/ /This report/ describes a 27-year-old subject who developed rhinitis and asthma symptoms 1 year after starting to prepare a certain kind of sausage. He was previously diagnosed as having allergy to coconut, banana, and kiwi and allergic rhinitis to horse, cat, dog, and cow. A positive immediate skin prick test (SPT) for paprika (dry powder of Capsicum annuum [Solanaceae]), coriander (Coriandrum sativum [umbelliferous]), and mace (shell of nutmeg, Myristica fragrans [Myristicaceae]) at a concentration of 10% (wt/vol) was obtained. SPT with other sausage ingredients, mites, pollens, and molds were negative. By EIA, specific /immunoglobulin/ E antibodies to paprika, coriander, and mace were demonstrated. By EIA-inhibition assays, a partial cross-reactivity was found among /immunoglobulin/ E-binding components from paprika and mace. The immunoblot analysis showed two /immunoglobulin/ E-reactive protein bands able to bind to /immunoglobulin/ E from mace of 20 and 40 /kiloDalton/ and two other bands from coriander extract of 50 and 56 /kiloDalton/. No bands were detected from paprika extract. Specific bronchial inhalation challenges showed an immediate asthmatic reaction to extracts from paprika, coriander, and mace with a maximum fall in /forced expiratory vol in 1 sec/ of 26%, 40%, and 31%, respectively, with no late asthmatic reactions. In summary, /the authors/ demonstrate that inhalation of dust from paprika, coriander, and mace can result in an /immunoglobulin/ E-mediated reaction to these spices. In this patient, occupational asthma was due to spices from botanically unrelated species.
The pharmacokinetics of dietary capsanthin were determined in four male volunteers with plasma essentially free of capsanthin at the beginning of the study. They received paprika juice for 1 week, equivalent to three doses of 5.4 umol capsanthin/day, for a total of 16.2 umol/day. The level of capsanthin in plasma reached a plateau (0.10-0.12 umol/L) between day 2 and day 7, and capsanthin was not detectable in plasma by day 16. Capsanthin was distributed in the plasma lipoproteins after 1 week as follows: very low density lipoprotein, 13 +/- 3%; low-density lipoprotein, 44 +/- 3%; and high-density lipoprotein, 43 +/- 3%.
In a /study/ involving the single ingestion of paprika juice (equivalent to 34.2 umol capsanthin) by the same men, the plasma concentration of capsanthin ranged from 0.10 to 0.29 umol/L at 8 hr after ingestion. In contrast, the elevation of the plasma concentration of an acyclic hydrocarbon carotenoid, lycopene, by a single ingestion of tomato soup (equivalent to 186.3 mmol lycopene) in the same subjects was minimal (0.02-0.06 mmol/L). The areas under the plasma concentration-time curves for capsanthin between 0 and 74 hr and for lycopene between 0 and 72 hr were 4.68 +/- 1.22 and 0.81 +/- 0.17 (umol.hr)/L, respectively. The half-lives were calculated to be 20.1 +/- 1.3 hr for capsanthin and 222 +/- 15 hr for lycopene. It was concluded that the clearance of capsanthin is much faster than that of lycopene, although capsanthin is transported into plasma lipoproteins in larger amounts.
The bioavailability of carotenoids from a paprika oleoresin (zeaxanthin, beta- cryptoxanthin, beta-carotene, capsanthin, capsorubin) was assessed in humans. After overnight fasting, nine volunteers ingested a single dose of a paprika oleoresin containing 6.4 mg zeaxanthin, 4.2 mg beta-cryptoxanthin, 6.2 mg beta-carotene, 35.0 mg capsanthin and 2.0 mg capsorubin. At different time points, the carotenoid pattern in the chylomicron fraction of whole blood was analyzed to evaluate carotenoid absorption. From the major carotenoids present in the paprika oleoresin, only zeaxanthin, beta-cryptoxanthin and beta-carotene were detectable in measurable amounts. Although the xanthophylls in paprika oleoresin were mainly present as mono- or diesters, only free zeaxanthin and beta-cryptoxanthin were found. The bioavailability of the pepper-specific carotenoids capsanthin and capsorubin from paprika oleoresin was found to be very low.
Synthesis of carotenoid-monosaccharide conjugates via azide–alkyne click-reaction
摘要：
Carotenoid pentynoates were coupled to protected and unprotected sugar azides via an azide-alkyne click-reaction using bis-triphenylphosphano-copper(I)-butyrate (C3H7COOCu(PPh3)(2)) complex. Protected sugars delivered the conjugates with excellent yields, whereas with unprotected ones amphipathic carotenoid-sugar derivatives were obtained in good or moderate yields in a simple way. (C )2016 Elsevier Ltd. All rights reserved.
Cyclothiocarbamate derivatives as progesterone receptor modulators and methods of treating skin disorders
申请人：Wyeth
公开号：US20040014798A1
公开（公告）日：2004-01-22
The present invention provides methods of treating skin disorders includes delivering to a mammal a composition containing a compound of formula I, or tautomers thereof, in a regimen, wherein formula I is:
1
and wherein R
1
-R
5
and Q
1
are defined as described herein. Specifically, methods for treating acne, hirsutism, and conditioning the skin are described. Also provided are novel PR modulators of formula II.
POLYMER-CARBOHYDRATE CONJUGATES FOR DRUG DELIVERY TECHNOLOGY
申请人：Wu Nian
公开号：US20150157721A1
公开（公告）日：2015-06-11
The invention comprises compounds, methods of making, and methods of using. The compounds may have a linear or cylic backbone and three or four appended functional groups: one or two lipohilic compounds including sterols or “fat soluble” vitamins, one or two hydrophilic polymer, and one or two carbohydrate. A group of polymer-carbohydrate conjugates having a central backbone and three appended functional groups are disclosed wherein one lipophilic compound is void of both steroid acids. The conjugate may have fatty acids as the primary lipophilic carrier, one hydrophilic polymer, and one carbohydrate. Specific functional groups may be selected for specific applications in formulating pharmaceuticals, cosmetics, nutriceuticals, and the like. Typical coupling reaction of the conjugates may involve one or more or combinations or in series of alkylation including N-alkylation or O-alkylation, etherification, esterification and amidation chemical processes. A variety of linkers between the backbone and functional groups may also be selected to modify the carriers or center backbones for the coupling reactions and optimize performance of the conjugates.
Total synthesis of capsanthin and capsorubin using Lewis acid-promoted regio- and stereoselective rearrangement of tetrasubsutituted epoxides
作者：Yumiko Yamano、Masayoshi Ito
DOI：10.1039/b710386g
日期：——
The synthesis of capsanthin 1 and capsorubin 2 was accomplished via the C(15)-cyclopentyl ketone 6 prepared by Lewis acid-promoted regio- and stereoselectiverearrangement of the epoxy dienal 5.
Hydroxylated nebivolol metabolites increase NO release from human endothelial cell preparations in a concentration dependent fashion following acute administration. In addition, hydroxylated nebivolol metabolites, including but not limited to 4-hydroxy-6,6′difluoro-, 4-hydroxy-5-phenol-6,6′difluoro-, and 4-hydroxy-8-pheno-6,6′difluoro-, have the ability to increase the capacity for NO release in human endothelial cells following chronic administration. This invention provides hydroxylated nebivolol metabolites and compositions comprising nebivolol and/or at least one hydroxylated metabolite of nebivolol and/or at least one additional compound used to treat cardiovascular diseases or a pharmaceutically acceptable salt thereof. In addition, this invention provides methods of treating and/or preventing vascular diseases by administering at least one hydroxylated metabolite of nebivolol that is capable of releasing a therapeutically effective amount of nitric oxide to a targeted site affected by the vascular disease. Also, this invention is directed to the treatment and/or prevention of migraine headaches administering at least one hydroxylated metabolite of nebivolol. This invention may also be used in conjunction with or as a single treatment of metabolic syndrome disorders.
[EN] CAROTENOID ANALOGS OR DERIVATIVES FOR THE INHIBITION AND AMELIORATION OF INFLAMMATION<br/>[FR] ANALOGUES OU DERIVES DE CAROTENOIDE POUR INHIBER ET REDUIRE L'INFLAMMATION
申请人：HAWAII BIOTECH INC
公开号：WO2005102356A1
公开（公告）日：2005-11-03
A method for inhibiting and/or ameliorating the occurrence of diseases in a human subject whereby a subject is administered a carotenoid analog or derivative, either alone or in combination with another carotenoid analog or derivative. In some embodiments, the administration of analogs or derivatives of carotenoids may inhibit and/or ameliorate the occurrence of diseases in subjects. In some embodiments, analogs or derivatives of carotenoids may be water-soluble and/or water dispersible. Maladies that may be treated with analogs or derivatives of carotenoids embodied herein may include diseases that provoke or trigger an inflammatory response. In an embodiment, asthma may be treated with analogs or derivatives of carotenoids embodied herein. In an embodiment, administering analogs or derivatives of carotenoids embodied herein to a subject may control or affect the bioavailability of eicosanoids. In an embodiment, atherosclerosis may be treated with analogs or derivatives of carotenoids embodied herein. In an embodiment, administering the analogs or derivatives of carotenoids embodied herein to a subject may control or affect the bioavailability of 5-LO-catalyzed eicosanoid metabolites. In an embodiment, 5-LO-catalyzed eicosanoid metabolites that may be controlled or affected by administering analogs or derivatives of carotenoids to a subject may include proinflammatory effector molecules (e.g., leukotrienes).
