Aluminum is poorly absorbed following either oral or inhalation exposure and is essentially not absorbed dermally. The bioavailability of aluminum is strongly influenced by the aluminum compound and the presence of dietary constituents which can complex with aluminum and enhance or inhibit its absorption. Aluminum binds to various ligands in the blood and distributes to every organ, with highest concentrations found in bone and lung tissues. In living organisms, aluminum is believed to exist in four different forms: as free ions, as low-molecular-weight complexes, as physically bound macromolecular complexes, and as covalently bound macromolecular complexes. Absorbed aluminum is excreted principally in the urine and, to a lesser extent, in the bile, while unabsorbed aluminum is excreted in the faeces. (L739)
The main target organs of aluminum are the central nervous system and bone. Aluminum binds with dietary phosphorus and impairs gastrointestinal absorption of phosphorus. The decreased phosphate body burden results in osteomalacia (softening of the bones due to defective bone mineralization) and rickets. Aluminum's neurotoxicity is believed to involve several mechanisms. Changes in cytoskeletal protein functions as a results of altered phosphorylation, proteolysis, transport, and synthesis are believed to be one cause. Aluminum may induce neurobehavioral effects by affecting permeability of the blood-brain barrier, cholinergic activity, signal transduction pathways, lipid peroxidation, and impair neuronal glutamate nitric oxide-cyclic GMP pathway, as well as interfere with metabolism of essential trace elements because of similar coordination chemistries and consequent competitive interactions. It has been suggested that aluminum's interaction with estrogen receptors increases the expression of estrogen-related genes and thereby contributes to the progression of breast cancer (A235), but studies have not been able to establish a clear link between aluminum and increased risk of breast cancer (A15468). Certain aluminum salts induce immune responses by activating inflammasomes. (L739, A235, A236)
Not listed by IARC. IARC classified aluminum production as carcinogenic to humans (Group 1), but did not implicate aluminum itself as a human carcinogen. (L135) A link between use of aluminum-containing antiperspirants and increased risk of breast cancer has been proposed (A235), but studies have not been able to establish a clear link (A15468).
Aluminum targets the nervous system and causes decreased nervous system performance and is associated with altered function of the blood-brain barrier. The accumulation of aluminum in the body may cause bone or brain diseases. High levels of aluminum have been linked to Alzheimer's disease. A small percentage of people are allergic to aluminium and experience contact dermatitis, digestive disorders, vomiting or other symptoms upon contact or ingestion of products containing aluminium. (L739, L740)
Inhalating aluminum dust causes coughing and abnormal chest X-rays. A small percentage of people are allergic to aluminium and experience contact dermatitis, digestive disorders, vomiting or other symptoms upon contact or ingestion of products containing aluminium. (L739, L740)
NOVEL LINKER DRUGS COMPRISING PHOSPHOANTIGENS, NOVEL CONJUGATES AND THEIR USE IN THERAPY
摘要：
The present invention relates to novel linker drug compounds based on specific phosphoantigens (pAg) with the general structure reflected in formula (I), wherein L represents a linking moiety (linker) and, W1, W2, X1-5, x, m, n and R1-4are as defined in the specification. Further provided are conjugates comprising a targeting moiety, preferably a tumor-targeting antibody or antigen binding fragment thereof, covalently linked to a linker drug compound according to the invention. Such conjugates can be used, for example, in the treatment of diseases such as cancer, infection, or autoimmune disease.
A stabilized preparation which comprises: a unstable drug in a polyethylene glycol-containing preparation; and a coating agent comprising a copolyvidone instead of polyethylene glycol with which the drug is coated.
Heterocyclics useful as fungicides and fungicidal compositions thereof
申请人：Hoffmann-La Roche Inc.
公开号：US04241058A1
公开（公告）日：1980-12-23
Heterocyclic compounds characterized by the formula ##STR1## wherein R.sub.1, R.sub.3, R.sub.4, R.sub.5, R.sub.6, X and z are as hereinafter set forth, prepared, inter alia, by reacting a compound characterized by the formula ##STR2## with an amine characterized by the formula ##STR3## wherein R.sub.1, R.sub.3, R.sub.4, R.sub.5, R.sub.6, X and Y are as hereinafter set forth, are described. The end products are useful as fungicidal agents.
(Nitrofuryl)pyrazoles, their synthesis and use, and compositions
申请人：Byk Gulden Lomberg Chemische Fabrik GmbH
公开号：US04093812A1
公开（公告）日：1978-06-06
3-(5-Nitro-2-furyl)pyrazoles unsubstituted in the 5-position and 5-(5-nitro-2-furyl)pyrazoles unsubstituted in the 3-position are antimicrobials and disinfectants. The compounds are structurally represented by one of the formulae: ##STR1## wherein A is --CHO, --CN, --COOH, a protected or derived aldehyde group or a protected or derived carboxylic acid group; B is 5-nitro-2-furyl; R.sup.1 is --H, substituted or unsubstituted hydrocarbyl (saturated or unsaturated; acyclic, alicyclic or aromatic; or araliphatic); substituted or unsubstituted (cycloaliphatic or aromatic) heterocyclic or acyl (carboxylic or carbonic acid); R.sup.2 is --H; and n is a positive whole number of at most 2.
Azabicycloheptanes and process for their preparation
申请人：Ciba-Geigy Corporation
公开号：US04883877A1
公开（公告）日：1989-11-28
Compounds of the formula I ##STR1## in which R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are, for example, H, alkyl, cycloalkyl, aryl or alkaryl are suitable as an ammonium salt-forming component for acid pharmaceutical active ingredients, and in particular for the preparation of azabicyclo[3.1.1.]heptane-substituted alkanediphosphonic acids for the treatment of diseases which can be attributed to disturbances in calcium metabolism.
Partial Reduction of Esters to Aldehydes Using a Novel Modified Red-Al Reducing Agent
作者：Won Kyu Shin、Daehoon Kang、Duk Keun An
DOI：10.5012/bkcs.2014.35.7.2169
日期：2014.7.20
Received February 11, 2014, Accepted March 12, 2014Key Words : Red-Al, cis-2,6-Dimethyl morpholine, Partial reduction, Ester, AldehydeAldehydes are valuable building blocks and reactive inter-mediates in organic synthesis. The general and classicalsyntheses of aldehydesfrom esters involve reduction-oxida-tion and partial reduction using efficient partial reducingagents. Obviously, one-step partial
