Abstract: Provided are reagents and methods useful for the synthesis of guanidinylated compounds. Also provided are methods for assaying molecules, including guanidinylated molecules that modulate viral infection and replication.

Abstract: A 3-methylthiopropanal is produced by a method comprising the step of supplying an acrolein and a methyl mercaptan together or sequentially with an acidic compound and a basic compound into a reaction system to react the acrolein with the methyl mercaptan, wherein the basic compound is used in an amount of about 0.3 mol or less per mol of the acidic compound. In accordance with the present invention, a 3-methylthiopropanal with high quality is produced while suppressing the production of by-products having high boiling points.

Abstract: Nanobacteria contribute to pathological calcification in the human and animal body, including diseases such as kidney stones, salivary gland stones, dental pulp stones and atherosclerosis. The present invention provides methods for sterilizing articles contaminated with nanobacteria. The present invention also provides methods of treating patients infected with nanobacteria. In particular, the present invention provides a method for preventing the recurrence of kidney stones in a patient that has suffered from kidney stones, comprising administration of an antibiotic, a bisphosphonate, or a calcium chelator, either alone or in combination, in an amount effective to inhibit or prevent the growth and development of nanobacteria.

Abstract: The invention describes an antibiotic coating for porous bodies and its use. Into the porous system of non-metallic porous bodies and of metallic porous bodies, a coating made of at least one antibiotic salt that is hardly soluble in water or in an aqueous environment from the group of the netilmicin laurate, the netilmicin myristate, the netilmicin dodecyl sulfate, the sisomicin laurate, the sisomicin myristate, the sisomicin dodecyl sulfate, the gentamicin laurate, the gentamicin myristate, the clindamycin laurate, the amikacin laurate, the amikacin myristate, the amikacin dodecyl sulfate, the kanamycin laurate, the kanamycin myristate, the kanamycin dodecyl sulfate, the tobramycin laurate, the tobramycin myristate, the tobramycin dodecyl sulfate, the ciprofloxacin myristate, the vancomycin dodecyl sulfate, the vancomycin laurate, the vancomycin myristate, the vancomycin teicoplanin and the clindamycin teicoplanin is introduced. The antibiotically coated, porous bodies are used as implants.

Abstract: Conjugates of a saccharide and an acetamidino- or guanidino-compound, of the formula: wherein A is CH3 or NH2; X is a linear or branched C1-C8 alkyl chain optionally containing hydroxy, amino and/or oxo groups; n is an integer from 1 to 6, and Sac is the residue of a mono-or oligo-saccharide, provided that when A is NH2 and X is -(CH2)3—CH(NH2)—C(=O)-, the monosaccharide residue is not substituted at the position 1, and n is an integer from 2 to 6 when Sac is the residue of an oligosaccharide, are useful as antiviral, particularly as antiretroviral, agents, and can be used either alone or together with other compounds used in AIDS treatment such as AZT and/or protease inhibitors, for the treatment of HIV-infection, AIDS and manifestations of AIDS such as Kaposi sarcoma.

Abstract: The present invention is directed to novel 2-aminobenzamide thereof, represented by the general Formula I: where R1-R3, X, and A—D are defined herein. The present invention also relates to the discovery that compounds having Formula I are potent inhibitors of caspases and apoptotic cell death. Therefore, the inhibitors of this invention can retard or block cell death in a variety of clinical conditions in which the loss of cells, tissues or entire organs occurs.

Abstract: The present invention relates to novel compositions and, more particularly, to a class of compounds having specific quaternized amine based upon a guerbet amido amine linked to specific phosphate esters. Guerbet acids are a specific group of branched acids that have no unsaturation present in the group, but nonetheless are liquid, and are outstanding skin care emollients, providing great spreadability on the skin. In addition this material is not toxic to human skin and is well tolerated by human tissue making it suitable for use in the preparation products for personal care applications.

Abstract: A patient suffering from an endobronchial infection is treated by administering to the patient for inhalation a dose of less than about 4.0 ml of a nebulized aerosol formulation comprising from about 60 to about 200 mg/ml of an aminoglycoside antibiotic, such as tobramycin, in a physiologically acceptable carrier in a time period of less than about 10 minutes. Unit dose devices for storage and delivery of the aminoglycoside antibiotic formulations are also provided.

Abstract: This invention relates to anti-viral agents that target RNase H substrates of reverse transcriptase and methods of using these agents to inhibit reverse transcriptase and viral replication. The invention also relates to methods for screening anti-viral agents capable of inhibiting the RNase activity of reverse transcriptase by targeting RNA-DNA hybrid substrates.

Abstract: Provided are reagents and methods useful for the synthesis of guanidinylated compounds. Also provided are methods for assaying molecules, including guanidinylated molecules that modulate viral infection and replication.

Abstract: Compositions and methods are provided for prophylactic or therapeutic treatment of a mammal for hearing impairments involving neuronal damage, loss, or degeneration, preferably of spinal ganglion neurons, by administration of a therapeutically effective amount of a trkB or trkC agonist, particularly a neurotrophin, more preferably NT-4/5. Also provided are improved compositions and methods for treatments requiring administration of a pharmaceutical having an ototoxic side-effect, wherein the improvement includes administering a therapeutically effective amount of a trkB or trkC agonist to treat the ototoxicity.

Abstract: This invention relates to a method of treating an inherited disease due to a point mutation producing a stop codon by administering an effective dose of an aminoglycoside antibiotic or a derivative thereof. Mdx mouse, which is an animal model for Duchenne muscular dystrophy, has been successfully treated with intramuscularly administered 1 and 5 mg gentamicin, which had for effect to suppress the premature stop mutation by inserting an amino acid at the stop codon. Dystrophin positive muscle fibers not different in number from those of normal mouse were detected at the dose of 5 mg gentamicin.

Abstract: Aminoglycoside antibiotics are used to treat genetic ophthalmic diseases caused by premature “stop” mutations.

Abstract: The present invention is directed to a method for the treatment of severe chronic bronchitis, i.e., bronchiectasis, using a concentrated aminoglycoside antibiotic formulation delivering the antibiotic to the lung endobronchial space, including alveoli, in an aerosol or dry powder having a mass medium diameter predominately between 1 to 5 microns.

Abstract: The invention provides a method of potentiating the activity of antibacterial agents that act on bacterial cell walls, comprising the step of administering to a subject an antibacterial agent and an aminoglycoside to attain a peak concentration of at least 4 mg/l of aminoglycoside and thereafter maintaining the aminoglycoside at a concentration of up to 4 mg/l for at least 1 hour. Compositions comprising an antibacterial agent and an aminoglycoside for efficacious treatement of bacterial infection are also provided.

Abstract: A method for treating or preventing atherosclerosis in a mammal is described. An agent for inhibiting interaction between P-selectin and a ligand of P-selectin is provided. The agent is administered to a mammal in need of such treatment to cause this inhibition to occur.

Abstract: Method of eliciting in a mammalian host a protective immune response to Helicobacter infection and treatment of Helicobacter infection by administering to the host an immunogenically effective amount of a Helicobacter urease or urease subunits as antigen. Vaccine compositions are also provided.

Abstract: The present invention relates to synthetic methods for the production of both optically active and racemic 5,5-disubstituted-3,4-dihydroxy-2(5H)-furanones; 5-[(4-aryl)-3-butynyl]-3,4-dihydroxy-2(5H)-furanones; 5-(2-arylthio)ethyl-3,4-dihydroxy-2(5H)-furanones; and 5-(2-aryloxy)ethyl-3,4-dihydroxy-2(5H)-furanones. This invention further relates to the use of the above mentioned compounds as anti-inflammatory agents through their action as mixed inhibitors of lipid peroxidation, 5-lipoxygenase, cyclooxygenase-1 and cyclooxygenase-2. The invention further relates to the use of such compounds in the treatment of chronic inflammatory disorders such as asthma, rheumatoid arthritis, inflammatory bowel disease, atherosclerosis, acute respiratory distress syndrome, and central nervous system disorders such as Alzheimer's and Parkinson's disease wherein reactive oxygen species and inflammatory mediators are contributing deleterious factors.

Abstract: The invention relates to the use of methanebisphosphonic acid derivatives of formula I for the treatment of fractures. These compounds have surprisingly been found to promote a more rapid and stronger fracture healing in mammals including man.

Abstract: Protein targets for disease intervention through inhibition of nucleic acid metabolism are disclosed. Novel polypeptides for one such target, DNA-dependent ATPase A, and novel polynucleotides encoding DNA-dependent ATPase A are disclosed. Phosphoaminoglycoside compounds which act on such protein targets to inhibit nucleic acid metabolism. In addition, screening assays for identifying compounds that inhibit nucleic acid-dependent ATPase activity, including, but not limited to, DNA-dependent ATPase A, are disclosed. Such compounds are useful in the treatment of diseases, including but not limited to cancer and infectious disease, through disruption of nucleic acid metabolism and induction of apoptosis. Moreover, methods for prevention and treatment of diseases including, but not limited to cancer and infectious disease are disclosed.

Abstract: A stabilized two-part disinfecting system comprising a first part and a second part adapted to be mixed to yield an aqueous disinfecting composition. The first part contains a non-esterifying acid and an alcohol-containing humectant or antifreeze, while the second part contains a salt of an organic acid and an optional metal chlorite. Methods for making a disinfecting composition by mixing the two-part disinfecting system, as well as for disinfecting substrates by contact therewith, are also disclosed.

Abstract: Method of eliciting in a mammalian host a protective immune response to Helicobacter infection by administering to the host an immunogenically effective amount of a Helicobacter urease or urease subunits as antigen. Vaccine compositions are also provided.

Abstract: The present invention relates generally to a method for, and pharmaceutical compositions useful in, the prophylaxis and/or treatment of cardiac dysfunction in a mammal by the administration of an effective amount of an agent capable of blocking or inhibiting the effect or release of inositol(1,4,5)trisphosphate in cardiac tissue.

Abstract: The invention described herein provides for methods of screening for compounds that can be used to prevent or inhibit the growth of microbial eukaryotes, particularly plant or animal pathogens. The screening methods of the invention involve the step of screening compounds for the ability to inhibit Group I intron I splicing. In addition, to directly screening for compounds that inhibit Group I intron splicing, the screening methods of the invention include screening for compounds that bind to prokaryotic 16S ribosomal RNA because of the correlation, described herein, between group I intron inhibition and binding to prokaryotic 16S ribosomal RNA. The range of possible compounds for screening by the screening methods of the invention is preferably limited to 2-deoxystreptamine derivatives.Another aspect of the invention is to provide methods of treating or preventing infections with eukaryotic microbes by administering an effective amount of a compound that inhibits group I intron splicing.

Abstract: There is provided an immunogenic composition capable of inducing protective antibodies against Helicobacter infection characterized in that it comprises:i) at least one sub-unit of a urease structural polypeptide from Helicobacter pylori (SEQ ID NOS:22,26), or a fragment thereof, said fragment being recognized by antibodies reacting with Helicobacter felis urease (SEQ ID NOS:20-21), and/or at least one sub-unit of a urease structural polypeptide from Helicobacter felis (SEQ ID NOS:20-21), or a fragment thereof, said fragment being recognized by antibodies reacting with Helicobacter pylori urease (SEQ ID NOS:22-26);ii) and/or, a heat shock protein (Hsp), or chaperonin, from Helicobacter, or a fragment of said protein.The preparation, by recombinant means, of such immunogenic compositions is also provided.

Abstract: The subject invention encompasses methods for prevention and treatment of a human or lower animal subject having a urogenital disorder caused or mediated by one or more parasitic protozoa comprising administering to the subject bismuth and one or more antimicrobials. The subject invention also encompasses compositions comprising bismuth and one or more antimicrobials for the prevention and treatment of a human or lower animal subject having a urogenital disorder caused or mediated by one or more parasitic protozoa.

Abstract: As new dibekacin derivatives and new arbekacin derivatives are now provided 2"-amino-2"-deoxydibekacin, 2"-amino-5,2"-dideoxydibekacin, 2"-amino-2"-deoxyarbekacin, 2"-amino-5,2"-dideoxyarbekacin, 2"-amino-5,2"-dideoxy-5-epi-fluoroarbekacin and 2"-amino-5,2"-dideoxy-5-epi-aminoarbekacin which all exhibit high antibacterial activity against a wide variety of gram-positive and gram-negative bacteria, including resistant bacteria such as methicillin-resistant Staphylococcus aureus and which are of low toxicity to mammals and are useful as antibacterial agent for treatment of bacterial infections.

Abstract: The present invention relates to novel amino glycoside salts of sucrose-octa-O-sulfonic acid of formula I:([sucrose-octa-O-sulfonic acid.sup.8- ]-[R-(NH.sub.3.sup.+).sub.x ].sub.y -M.sub.z.sup.n+) (I)(x.multidot.y)+(z.multidot.n)=8x.multidot.y.epsilon.N.vertline.[4.ltoreq.x.multidot.y.ltoreq.8], wherein N is the set of natural numbers,x.epsilon.Z.vertline.[4.ltoreq.x.ltoreq.6], wherein Z is the set of integersz.epsilon.N.vertline.[0.ltoreq.z.ltoreq.4],n.epsilon.Z.vertline.[1.ltoreq.n.ltoreq.3],wherein R is a sugar moiety of an amino glycoside and M is a metal ion or an ammonium ion, said compounds being useful for treating ulcerations of the stomach and duodenum.

Abstract: Disclosed is a method for the inhibition of binding of a ligand to an RNA, the inhibition being mediated by a small organic molecule which binds to the RNA, thereby inhibiting ligand binding. A preferred class of small organic molecules are the 2-deoxystreptamine (2-DOS) aminoglycosides. Disclosed herein are members of the 2-DOS class that are useful for the inhibition of binding of Rev to an RNA containing an RRE. In an HIV infected cell, a consequence of the inhibition of the ability of Rev to bind to the RRE in HIV encoded transcripts is inhibition of HIV replication.

Abstract: As new compounds are now synthetized 5-deoxy-5,5-difluoro derivatives of aminoglycosidic antibiotics of neamine, kanamycin A-series, kanamycin B-series, gentamicin-series and seldomycin-series. Further, the 1-N-(.alpha.-hydroxy-.omega.-aminoalkanoyl) derivatives are synthetized from 5-deoxy-5,5-difluorokanamycins A and B, as well as their analogues now obtained. The 5-deoxy-5,5-difluoro derivatives of the aminoglycosidic antibiotics now provided according to this invention have such antibacterial activities enhanced much more than or equal to those of the respectively corresponding parent aminoglycosidic antibiotics, while these 5-deoxy-5,5-difluoro derivatives exhibit values of the 50% lethal dosage (LD.sub.50) which are improved remarkably better when they are intravenously administered to mice, so that they have remarkedly reduced toxicities to mammals.

Abstract: As new dibekacin derivatives and new arbekacin derivatives are now provided 2"-amino-2"-deoxydibekacin, 2"-amino-5,2"-dideoxydibekacin, 2"-amino-2"-deoxyarbekacin, 2"-amino-5,2"-dideoxyarbekacin, 2"-amino-5,2"-dideoxy-5-epi-fluoroarbekacin and 2"-amino-5,2"-dideoxy-5-epi-aminoarbekacin which all exhibit high antibacterial activity against a wide variety of gram-positive and gram-negative bacteria, including resistant bacteria such as methicillin-resistant Staphylococcus aureus and which are of low toxicity to mammals and are useful as antibacterial agent for treatment of bacterial infections.

Abstract: A method of killing microorganisms which form a biofilm on a tissue or implant surfaces in a patient, and which are refractory to a biocide at a dose which is effective to kill the microorganism in planktonic form. The effect of the biocide is potentiated, to an effective killing level, by applying an electric field across the surface containing the biofilm.

Abstract: Methods, for the treatment of humans and lower animal subjects having a gastrointestinal disorder, comprising administering bismuth and administering an antimicrobial. From about 50 to about 5000 milligrams of bismuth are administered, per day, for from 3 to 56 days. A safe and effective amount of antimicrobial is administered for from 1 to 21 days. Preferred processes also include a step for performing a diagnostic test on the subject for detection of a campylobacter-like organism infection of the subject. The invention also provides compositions containing a safe and effective amount of bismuth and a safe and effective amount of antimicrobial.

Abstract: A new and substantially improved type of lipid vesicle, called stable plurilamellar vesicles (SPLVs), are described, as well as the process for making the same and X-ray diffraction methods for identifying the same. SPLVs are characterized by lipid bilayers enclosing aqueous compartments containing one or more entrapped solutes, the concentration of such solutes in each aqueous compartment being substantially equal to the emunization of solutes used to prepare the SPLVs. The bilayers of SPLVs are substantially non-compressed. SPLVs are stable during storage and can be used in vivo for the sustained release of compounds and in the treatment of disease.

Abstract: Compositions and methods useful for the prevention or treatment of a human or animal disorder or for the regulation of the human or animal physiological condition are provided. The compositions used comprise, in admixture, a biologically-effective amount of a drug specific for the disorder or condition and a biocompatible, water-soluble, amphiphilic steroid, other than a natural bile salt, which is capable of increasing drug permeability of the human or animal body surface across which the drug is to be administered, in an amount effective to increase the permeability of the surface to the drug.

Abstract: Disclosed are antibiotic compositions for topical administration comprising an aminoglycoside, a benzylpyrimidine and a sulfonamide.

Abstract: Novel substituted 2,3-diphenyl-1,2-dihydroquinoxalines are useful for promoting growth and improving feed conversion efficiencies in meat-producing animals. In addition, the novel compounds are useful for controlling coccidiosis in poultry.

Abstract: Crosslinked copolymers of monomeric aminosaccharides such as aminoglycosidic antibiotics, e.g. neomycin, or of polymeric aminosaccharides, e.g., chitosan, with dialdehydes are useful antihypercholesterolemic agents due to their ability to bind with bile acids. These copolymers are insoluble in acidic solutions but are swellable to at least about 2.times. their original weight.

Abstract: As new compound are now provided ten compounds, namely 1-N-{(2R,3R)-4-amino-3-fluoro-2-hydroxybutyryl}kanamycin A; 1-N-{(2R,3R)-4-amino-3-fluoro-2-hydroxybutyryl}-2',3'-dideoxykanamycin A; 1-N-{(2R,3R)-4-amino-3-fluoro-2-hydroxybutyryl}-2',3'-dideoxy-2'-fluorokan amycin A; 1-N-{(2R,3R)-4-amino-3-fluoro-2-hydroxybutyryl}-5-deoxy-5-fluorokanamycin A; 1-N-{(2R,3R)-4-amino-3-fluoro-2-hydroxybutyryl}-kanamycin B; 1-N-{(2R,3R)-4-amino-3-fluoro-2-hydroxybutyryl}-3'-deoxykanamycin B; 1-N-{(2R,3R)-4-amino-3-fluoro-2-hydroxybutyryl}-3',4'-dideoxykanamycin B; 1-N-{(2R,3R) -4-amino-3-fluoro-2-hydroxybutyryl}-5-deoxy-5-fluorokanamycin B; 1-N-{(2R,3R)-4-amino-3-fluoro-2-hydroxybutyryl}-5,3'-dideoxy-5-fluorokanam ycin B; and 1-N{(2R,3R)-4-amino-3-fluoro-2-hydroxybutyryl}-5,3',4'-trideoxy-5-fluoroka namycin B, which are all useful as antibacterial agent in the therapeutic treatment of bacterial infections.

Abstract: An aminoglycoside compound represented by the following formula (I) ##STR1## wherein one of R.sub.1 and R.sub.2 represents a hydrogen atom, and the other represents a methyl group,R.sub.3 represents a hydrogen atom or a hydroxyl group,R.sub.4 represents a hydrogen atom, a hydroxyl group or a methoxy group,n represents an integer of 1 to 5,W represents a divalent group of the formula --NHCO.fwdarw., --CONH.fwdarw., --COO.fwdarw., or --S.fwdarw. in which .fwdarw. represents a bond to X, andX represents (i) a single bond or (ii) a C.sub.1 -C.sub.20 trivalent acyclic saturated hydrocarbon group, andY and Z are separately defined according to the cases (i) and (ii) above, and its pharmaceutically acceptable acid addition salt; and a process for producing the above aminoglycoside compound. A pharmaceutical composition comprising the above aminoglycoside compound is useful as an antibiotic.

Abstract: New compound, 3',4'-dideoxy-3'-fluorokanamycin B is now provided, which is useful as antibacterial agent.3',4'-Dideoxy-3'-fluorokanamycin B is prepared by a process comprising halogenating an N,O-protected derivative of 3'-deoxy-3'-fluoro-4'-O-sulfonylkanamycin B with a metal halide, reducing the resulting 4'- halogenated 3'-deoxy-3'-fluorokanamycin B derivative to convert its 4'-halo group into a hydrogen atom, and thereby to produce an N,O-protected derivative of 3',4'-dideoxy-3'-fluorokanamycin B, and removing the remaining amino-protecting groups and the remaining hydroxyl-protecting groups from the reduction product by conventional deprotecting methods.

Abstract: Novel substituted 2,3-diphenyl-1,2-dihydroquinoxalines are useful for promoting growth and improving feed conversion efficiencies in meat-producing animals. In addition, the novel compounds are useful for controlling coccidiosis in poultry.

Abstract: Novel lysine esters used as absorption enhancing agents for gastrointestinally and rectally administered drugs. Also provided are processes for preparation of said lysine ester compounds as well as pharmaceutical formulations and methods for their use as absorption enhancing agents.

Abstract: New compounds, 2',3'-dideoxy-2'-fluorokanamycin A and 1-N-(.alpha.-hydroxy-.omega.-aminoalkanoyl) derivatives thereof, particularly 1-N-(DL- or L-3-amino-2-hydroxypropionyl)- and 1-N-(L-4-amino-2-hydroxybutyryl)-2',3'-dideoxy-2'-fluorokanamycins A are now provided, which are each useful as antibacterial agent. 2',3'-Dideoxy-2'-fluorokanamycin A is prepared by a process comprising condensing a 6-azido-4-O-protected-2,3,6-trideoxy-2-fluoro-.alpha.-D-ribo-hexopyranosyl bromide with the 4-hydroxyl group of a 6-O-(2',4',6'-tri-O-protected-3'-N-protected-3'-amino-3'-deoxy-.alpha.-D-g lucopyranosyl)-1,3-bis-N-protected-2-deoxystreptamine, reducing the resulting condensation product to convert its azido group into an amino group, and removing the remaining amino-protecting and hydroxyl-protecting groups from the reduction product.

Abstract: Aminoglycoside derivatives and pharmaceutically acceptable salts thereof which are useful as prophylactic and therapeutic agents for infectious diseases caused by pathogenic microorganisms, and a pharmaceutical composition comprising the same.

Abstract: A preparation for percutaneous administration of nitroglycerine, said preparation comprising nitroglycerine incorporated in a cream base in an amount not less than about 0.05% by weight based on the total weight of the preparation. The composition may also contain other medicaments, the bioavailability of which is enhanced by the nitroglycerine. The action of the preparation against for example angina may be brought about by having an appropriate amount of nitroglycerine or as additional medicament another medicament active against angina. The preparation may contain an hydroxyalkylcellulose which may provide, in combination with a waxy component in the cream, for example a higher aliphatic alcohol, a prolonged release effect. The preparation has advantages particularly as regards bioavailability over prior uniphasic ointments.

Abstract: The invention relates to a synergistic antibiotic composition useful for the treatment of respiratory, gastrointestinal or urinary infections and septicaemia of domestic animals. The composition comprises tiamulin hydrogen fumarate and an aminoglycoside antibiotic or a pharmaceutically acceptable salt thereof in a weight ratio of 5:1 to 1:5. The active components are admixed or diluted with a carrier, used in veterinary therapy, in a weight ratio of 1:1 to 1:50 and formulated for oral or parenteral application.

Abstract: Aminoglycosides and aminoglycoside-aminocyclitols which have been oxygen-radical activated show a broad spectrum of antibacterial activity. The activated compounds are able to penetrate the cell membranes of bacteria and show substantially enhanced activity as compared to the parent unactivated compound.

Abstract: A new compound, 3'-fluoro-3'-deoxykanamycin A is now provided, which is active against gram-negative and gram-positive bacteria, including kanamycin-resistant strains of bacteria and is useful as antibacterial agent for therapeutic treatment of bacterial infections. This new compound is produced by a process comprising reacting a 6-azido-2,4-di-O-protected-3,6-dideoxy-3-fluoro-.alpha.-D-glucopyranosyl bromide with the 4-hydroxyl group of a 6-O-(2'-O-protected-3'-N-protected-3'-amino-4',6'-di-O-protected-3'-deoxy- .alpha.-D-glucopyranosyl)-1,3-bis-N-protected-2-deoxystreptamine, reducing the azido group of the resulting reaction product into an amino group, and removing the remaining protective groups from the reduction product.

Abstract: Flavonoid phosphates of aminoglycoside antibiotics are useful sparingly soluble salts, e.g., for achieving a depot effect.