650 results about "Colchicine" patented technology

Compositions comprising colchicine and at least one amino-salicylic acid derivative, preferably olsalazine is used for treatment of prophylaxis of constipation.

Methods for treating chronic wounds in a human are described by topically administering a dermatological composition comprising a TNF antagonist, a TACE inhibitor, a neutrophil antagonist, or a combination of a TNF antagonist and / or TACE inhibitor and a neutrophil antagonist. The TNF antagonist administered includes alefacept, efalizumab, etanercept, adalimumab, and onercept, while the neutrophil antagonist administered includes dapsone, colchicine, its analogs and prodrugs. The combination of TNF-antagonist and neutrophil antagonist administered includes sulfapyridine, sulfasalazine, mesalamine, and derivatives and prodrugs thereof. The topical compositions can be formulated to include the one or more of the antagonists in dissolved, semi-dissolved, and micro-particulate states.

The invention discloses a method for acquiring an aromatic rice strain by targeting a Badh2 gene via CRISPR / Cas9 gene editing technology. The method comprises the following steps: separately targeting sequences, recognizable by Cas9, of every exon and intron of an aromatic gene by using the CRISPR / Cas9 gene editing technology and then cutting a genomic DNA sequence to initiate DNA restoration so as to obtain an afunctional Badh2 gene; with the callus of Indica rice, japonica rice or glutinous rice as a receptor material of genetic transformation and an mature embryo, young ear, ovary or the like as explant, carrying out induction so as to obtain a diploid callus, introducing a targeting vector into cells of the callus by using an Agrobacterium mediated transformation method, screening and identifying positive plants and separating the plants from a T1 colony so as to obtain an aromatic rice strain; and with anther, pollen, unfertilized ovary or the like as explant, carrying out induction so as to obtain a haploid callus, introducing the targeting vector into cells of the callus by using the Agrobacterium mediated transformation method, screening a positive callus, reduplicating the positive callus by using colchicine, carrying out differentiation to form seedlings and identifying genetic transformation positive plants so as to eventually obtain the aromatic rice strain.

There is disclosed herein a composition for treating gastrointestinal or neurological disorders, constipation, functional constipation, irritable bowel syndrome, diverticulitis, travelers diarrhea, chronic idiopathic nausea, IBD-associated constipation and diarrhea, pseudo-obstruction, diabetic gastroparesis, cyclic vomiting, reflux oesophagitis, autism enteropathy, flatulence, halitosis, chronic fatigue, bloating, proctalgia fugax, Parkinsons disease, MS, Alzheimers Disease, Motor Neurone Disease or autism, the composition comprising: (i) at least two anti-clostridial agents selected from the group consisting of: vancomycin, vancomycin derivatives, a multi-valent polymer of vancomycin, aminoglycosides, nitroimidazoles, ansamysins, nifuroxazide, colchicine, prucalopride, prokinetic agent and 5-aminosalicylic acid; or (ii) at least one anti-clostridial agent selected from the above combined with an opioid blocking agent. There is also disclosed herein a method of treating various gastrointestinal or neurological disorders, constipation, functional constipation, irritable bowel syndrome, diverticulitis, travelers diarrhea, chronic idiopathic nausea, IBD-associated constipation and diarrhea, pseudo-obstruction, diabetic gastroparesis, cyclic vomiting, reflux oesophagitis, autism enteropathy, flatulence, halitosis, chronic fatigue, bloating, proctalgia fugax, Parkinsons disease, MS, Alzheimers Disease, Motor Neurone Disease or autism, the method comprising administering orally, via enema or by suppository: (i) a composition of the invention; (ii) at least two anti-clostridial agents selected from the group consisting of: vancomycin, vancomycin derivatives, a multi-valent polymer of vancomycin, aminoglycosides, nitroimidazoles, ansamysins, nifuroxazide, colchicine, prucalopride, prokinetic agent and 5-aminosalicylic acid; or (iii) at least one anti-clostridial agent selected from the above and an opioid blocking agent to a patient in need of such treatment.

Formulations and methods of treating human patients suffering from a condition characterized by lymphoid cancer, autoimmune disease or B cell hyperproliferation are disclosed, the treatment comprising administering (1) a cytotoxic amount of an antibody having specific binding for CDIM epitopes on a B cell, and (2) a cytotoxic agent, including a chemotherapeutic agent, radioactive isotope, cytotoxic antibody, immunoconjugate, ligand conjugate, immunosuppressant, cell growth regulator and / or inhibitor, toxin, or mixtures thereof, including agents that disrupt the cytoskeleton of B cells, particularly vinca alkaloids or colchicine.

The invention discloses a colchicine bilayer sustained-release tablet which comprises a quick release layer and a sustained-release layer, wherein the quick release layer mainly consists of colchicine, a disintegrant, a filler, a lubricant and an adhesive; the sustained-release tablet mainly consists of colchicine, a sustained-release matrix, a retarding agent, a filler and an adhesive; the weight ratio of the colchicine in the quick release layer to the colchicine in the sustained-release layer is (0.25-0.42) : 1; and the weight ratio of the quick release layer to the sustained-release layer is 1: 2 to 1: 4. The invention also discloses a method for preparing the colchicine bilayer sustained-release tablet. The colchicine bilayer sustained-release tablet releases the drugs through the quick release layer to quickly achieve the effective blood drug concentration, slowly releases the drugs through the sustained-release layer to exert and sustain the stable and uniform effective blood drug concentration, reduces the drug taking times and lightens the toxic or side function.

The invention provides a novel tubulin inhibitor and an application thereof. The novel tubulin inhibitor is a series of substituted heterocyclic skeleton-based compounds with colchicine binding sites in tubulins as targets. The compounds have the following structure as shown in the specification, wherein the formula is as shown in the specification; n independently represents an integer of 0-5 under the condition that n is less than or equal to 5; A represents a monosubstituted or polysubstituted group; and the group is selected from H, C1-C20 acylamino, C1-C20 acyloxy, C1-C20 alkanoyl, C1-C20 alkoxycarbonyl, C1-C20 alkoxy, C1-C20 alkylamino, C1-C20 alkylcarboxy amino, aroyl, arylalkanoyl, carboxyl, cyano, halogen, hydroxyl, nitro and methylthienyl.

Embryogenesis from plant microspores is routinely induced with a 16-24 h temperature treatment of 32.5° C. Continuous culture at 25° C. results in pollen development. However, microspore treatment with anti-cytoskeletal agents, or protein synthesis inhibitors, at the non-inductive temperature of 25° C., can induce embryogenesis, thus demonstrating that heat shock is not required for embryogenic induction. Furthermore, when anti-microtubule agents (e.g. colchicine) are used, embryo induction and chromosome doubling occur simultaneously, thus generating doubled haploids, whereas heat induction generates haploids. Thus, the use of microtubule inhibitors will provide a simple one-step process to simultaneously induce embryogenesis and chromosome doubling for the production of fertile plants, thus providing minimal manipulation which will be very advantageous for genetic studies and plant breeding programs. As noted, heat shock induces haploids. A low level of chromosome doubling can be obtained by adding colchicine to microspore cultures during the heat treatment. However, the use of trifluralin with the heat treatment, to generate doubled haploid plants results in an improved recovery of fertile doubled haploid plants than previously shown in the prior art.

The invention provides a breeding method for the germ plasm of a new translocation line wheat-rye T2BL.1RS, which is characterized in that, distant hybridization is performed by taking common wheat variety Xiaoyan 6 as female parent and relative plant rye variety German White as male parent; seeds are acquired after immature embryo salvation culture, colchicine half root soaking method and chromosome doubling; backcross seeds are acquired after disease resistance identification, cytological identification and backcrossing utilizing the original parent Xiaoyan 6 as male parent; then after disease resistance identification and cytological identification, individual plants with excellent comprehensive characters are selected in direction for self crossing, and after continuous self cross selective breeding for six generations, the finally acquired individual plant is confirmed to be wheat-rye T2BL.1RS translocation line after identified by continuous total genome in situ hybridization and three-probe multicolor fluorescence in situ hybridization. The breeding method for the germ plasm of a new translocation line wheat-rye T2BL.1RS has the advantages that, the wheat-rye T2BL.1RS translocation line has high resistance to stripe rust, current prevalent fungus strain, powdery mildew and other important virus strains; the invention has excellent high yield character; the method lays an excellent germplasm base for the cultivation of breakthrough new wheat variety with disease resistance and high yield.

The present invention relates to a novel purpose of mangiferin compound for preventing and remedying hyperuricemia and gout. A study shows that the mangiferin compound has very strong anti-gout effect; 0.002mmol / kg (0.78mg / kg) of the dosage can reduce the serum uric acid level of a mouse with the hyperuricemia obviously; the mangiferin compound has higher activity than allopurinol and has little toxic and side effect; the maximum gastric infusion tolerance dose of the mouse is 47.4mmol / kg (20g / kg), which is lower than that of current clinical applied anti-gout medicines, such as colchicines, the allopurinol, sulphinpyrazone, etc.; the present invention can be applied to prepare for oral anti-gout medicines and health care products.

The invention discloses a colchicines gastric floating sustained-release tablet, which comprises active components of colchicines and pharmaceutic adjuvant according to the weight ratio of 1:24-1,999, wherein the pharmaceutic adjuvant comprises a hydrophilic gel framework material, a effervescing agent, a floating assistant material, a filler, a pH value regulator and a lubricant. The colchicines gastric floating sustained-release tablet can swell quickly in gastric juice or a similar gastric juice medium and can float on the gastric juice for at least 4 hours. The invention also relates to a method for preparing the colchicines gastric floating sustained-release tablet. The colchicines gastric floating sustained-release tablet can reach the effective blood-drug concentration quickly after being taken and then release drugs slowly, and can maintain the balanced blood-drug concentration so as to reduce the dose times, relieve the toxic side effect and improve the bioavailability.

The invention provides a method of breeding fourfold paulownia tomentosa in the combination of isolated culture by using placentas as explants and colchicine treatment, comprising the following twelve steps: a. choice of parent; b. using placentas as best explants; c. placenta callus inducement; d. double treatment of placenta callus; e. callus recovery cultivation after treatment; f. callus division cultivation; g. sprout rooting cultivation; h. transplanting of seedling; i. morphological authentication of paulownia tomentosa plant polyploidy; j. chromosome number authentication of paulownia tomentosa plant polyploidy; k. flow cytometry analysis authentication of paulownia tomentosa plant polyploidy; l. authentication of paulownia tomentosa plant polyploidy in flowering period, etc. Compared with adult plants of other multiploid paulownia tomentosa, the fourfold paulownia tomentosa is characterized by big flower, thick leaf, no burliness, and the like, obviously different from twofold paulownia tomentosa, and has perfect ornamental value and growing vantage. The technology not only can be directly applied to breeding new types of paulownia tomentosa but also builds a fine foundation for polyploid breeding of other trees.

The invention discloses a colchicine framework controlled-release tablet or capsule, which comprises colchicines and framework materials having controlled-release function, wherein the framework materials contain hydrophilic polymers of which the weight against the weight of the tablet is at least 20 percent and other pharmaceutic adjuvants; and the tablet or capsule comprises the following components in percentage by weight: 0.01 to 1.0 percent of colchicine, 20 to 85 percent of hydrophilic polymer, 1 to 30 percent of retarder, 20 to 60 percent of bulking agent, and 0.1 to 2 percent of lubricant. Release degree test results show that more than 90 percent of drugs are continuously released in vitro in 12 hours; and compared with the common tablet, the tablet or capsule has the advantages of obviously reducing daily taking frequency, lowering toxic and side effects of the drugs and improving the compliance and curative effect of patients.

The invention relates to a polyploid inducement method of Fritillaria pallidiflora Schrenk in vitro culture, which uses fresh bulb to be induced to produce adventitious buds. Inducement treatment is applied through cultivating in MS liquid medium with different density of colchicine to produce Fritillaria pallidiflora Schrenk polyploid plant. Bulb yield and medicinal components content of the plant are improved by changing chromosome ploidy to produce plant with good characteristics. Therefore, the problem of variety degeneration of Fritillaria pallidiflora Schrenk in a long-term course of Fritillaria pallidiflora Schrenk planting is overcomed. The method has the advantages that Fritillaria pallidiflora Schrenk polyploid can be obtained quickly with effectively improved content of active components and a shorter planting cycle.

The present invention provides a new type balloon dilation catheter which includes ballon and medication material coated on stent. Said medication material comes from one or two and more than two mixtures of heparin sodium, fiber degrading enzyme, serine proteinase, batroxobin, aspirin, genistein, hirudin and its recombined product, colchicine, sirolimus, biolimus, zotarolimus, tracrolimus, pimecrolimus, simvastatin, atorvastatin, pravastatin, ciclosporin, Anti-CD34, dexamethasone, bleomycin, plicamycin, daunomycin, mitomycin C, actinomycin D, taxol, celastrol, methopterin, 5-fluorouracil, cytarabine and 6-purinethol. The balloon is made of macromolecule nylon material, and the stimulation to blood vessel is far lower than the stent with metal structure.

The invention provides an excised mutagenesis tetraploid method of water melon and ploidy early stage certification technique, wherein dinitro toluene herbicide (DNH) is employed to substitute the conventional colchicines as inducer, whose function is to suppress the Mitosis in the metaphase of cell division through the mechanism of interfering spindle, so as to double the tissue cell chromosome. The method has the advantages of increased inducement success rate and substantially shortened time required for inducement.

The invention discloses a seed breeding method of a cabbage-type rape, wherein the seed breeding method is suitable for mechanical harvest and the cabbage-type rape is naturally capped in main inflorescence, is limited in siliques and is dwarf and compact in character. The seed breeding method includes following steps: (1) with the cabbage-type dwarf rapes 3H004 and compact-plant rapes 7399-8 as parents to performing hybridization to obtain an F1-generation; (2) in an early blooming period, selecting the buds being 3.0-4.0 mm in length on the main inflorescence and upper branched inflorescences of the F1 plant, perforning mutagenesis with EMS (ethyl methylsulfonate) and then performing colchicines doubling and microspore induction culture to obtain a DH separated population; (3) with plant height, branch characters, main inflorescence length, total silique number, growth period and oil-containing quantity and the like main characters, performing multi-year and multi-point in-field phenotype character identification to the DH separated population; and (4) selecting the variation materials which is naturally capped in main inflorescence, is limited in siliques, is lower than the upper branched inflorescences in height, is concentrated in blossom period and silique layers, and is dwarf and compact. The method can be used for obtaining the rape which is naturally capped in main inflorescence, is limited in siliques and is dwarf and compact in character. The method, when being popularized, can reduce planting cost of rapes and achieves excellent economical benefit.

The invention discloses a reagent formula for multiplying a plant chromosome by using a composite reagent without colchicines and a multiplying method. The plant chromosome is multiplied by using a composite formula prepared from multiple mitosis inhibitors and tubulin inhibitors; compared with a conventional chromosome multiplying method, the method has the characteristics of low toxicity, high efficiency and wide application range; cooperative use of three compounds such as a multiplying agent, an aid and a detoxicant with different functions is the key point of the reagent formula, and functions of improving multiplying effects and reducing medicine damage are achieved; by adopting the reagent formula, the problems that growth abnormity, malformation or even death of a treated plant material are generally caused, and the multiplication success rate is relatively low since the treated plant material is seriously damaged in conventional process that a plant chromosome is multiplied byusing colchicines, are solved; and more importantly, the problems that the colchicines are highly toxic, have potential carcinogeneses for mammals including human beings, and can cause serious harm to health of operators and environment security, can be solved.

The invention pertains to the field of rape breeding and discloses a method for seed selection and identification of a novel dwarf compact type rape adapting to high-density planting and mechanized harvesting. The rape of Variety 5148-2 with apreservation number of CCTCC-P200601 that is bred by Huazhong Agricultural University and yellow-seed rape of DH series YN90-1016 that is synthesized artificially in Canada are taken as seed-parents and crossbred to obtain F1. In inflorescence, the main anthotaxy of an F1 plant and the flower buds with a size ranging from 2.8mm to 3.8mm at the upper branches of the P1 plant are selected, and then chromosome doubling with colchicine and microspore culture are carried out successively to obtain the segregation populations of double haploid. Filed phenotypic characteristic identification are applied for years in various spots to the segregation populations; variant rape materials with five major traits, namely, stem length, branch trait, length of anthotaxy, quantity of silique and growth period differing from those of the common rape and dwarf, compact plant, smallish and acervate branches and main anthotaxy, concentrative florescence and compact pod bearing layers phenotypes are selected to obtain the novel dwarf compact type rape adapting to mechanized harvesting. The invention also discloses a method for molecular identification.

The invention discloses a cultivating method of the isolated microspores of brassica napus, which aims to solve the drawback of embryo index unavailable in prior art that, the production of microspore embryos can not be judged in the early stage. The invention is characterized in that, a whole filtered and sterilized NLN-13 hormone-free liquid culture medium comprising 45 to 55 mg / L colchicine is added to the prepared isolated microspores of brassica napus; the microspores are cultured in dark under a high temperature raging from 30 deg C to 35 deg C for two days; the materials having the microspore swell ratio large than 50% are chosen for subsequent induction culture. The cultivating method has the advantages that, the microspores having the microspore swell ratio large than 50% are chosen for subsequent induction culture, so the early rejection of the microspores that cannot produce embryos is facilitated; the workload is greatly reduced; the induction efficiency is improved, and the waste of time and resources is avoided.

The invention relates to a cultivation method of the triploid salvia, the steps of the invention are that: not completely ripe good salvia seeds are collected to put into the 1 / 2MS culture medium with colchicine for mutagenesis cultivation; then the seeds are transferred into a normal 1 / 2MS culture medium for cultivation, the root tip of the seedling is fetched to perform the ploidy identification of the chromosome after the preceding process of the chromosome, and the seedling with a chromosome quantity of 2n=4x=32 is the tetraploid salvia; the tetraploid salvia is taken as a female parent and the diploid salvia is taken as a male parent to perform the crossbreed and the obtaining seed is a triploid salvia plant. The nutrient organs such as the root, stem and leaf and so on of the triploid salvia plant obviously become bigger and present remarkable crossbreed advantages, and the root medicinal material output of the triploid salvia is increased by over 30 percent. Moreover, the triploid salvia has flowers, but no seeds, thus decreasing the nutrition consumption and the crossbreed advantages of the triploid salvia can be kept over 10 years through the asexual reproduction, which enhances the disease resistance and stress resistance with strong applicability, thus being applicable to planting in every part of the country. Besides, the crossbreed advantages produced by the novel variety triploid production are able to improve the output of the salvia medicinal material planting in a large scale.

The invention priovidese a new Broussonetia papyrifera mulberry tree hybrid distant hybridization and polyploidization breeding method. The method is characterized in that an inductive hybrid fruit callus doubling distant hybridization polyploid hybrid line is established by an embryo engineering and tissue culture technique of distant hybrids through a reproduction engineering kind improvement technology. The method comprises following steps: 1, obtaining distant hybrid fruits; 2, carrying out callus induction of the hybrid fruits; 3, carrying out colchicine treatment of the callus of the hybrid fruits; 4, carrying out recovery culture of treated calluses; 5, differentiating the calluses into bud seedlings; 6, differentiating the bud seedlings into roots; 7, transplanting tissue culture plants; 8, carrying out comparative observation and selection of survival plants; and 9, carrying out asexual propagation of the selected plants to form a stable kind (line). The method solves the problems comprising slow growth,weak adaptability, unclear trunk and bad material quality of present Broussonetia papyrifera, and allows the new polyploid Broussonetia papyrifera mulberry tree hybrid having the advantages of obvious trunk, strong adaptability and good material quality to be cultivated.

The invention belongs to the technical field of flower breeding, in particular to a method for doubly improving a marigold genotype by utilizing chromosomes, which is characterized in that male sterile dual-purpose line of a seed or a stem tip of marigold is treated by adopting a colchicine solution so as to enable the number of the chromosomes of the marigold to be doubled, thereby providing a breeding starting material of the improvement of the marigold genotype. The method comprises the following steps of: bud forcing treatment, colchicine doubling treatment, rinsing relief treatment, cultivation management, chromosome ploidy authentication and the like. The preferable treatment is described as follows: applying colchicine solution with concentration of 0.05 percent to marigold germinating seeds and soaking for 3 to 6 hours, and thus, the survival rate of plants is high, and the doubling efficiency also reaches 88.89 percent. The invention can effectively control the environment temperature and humidity when the seeds germinate; the repeatability of a test is high, the operation is convenient and time and labor are saved. The invention is suitable for the improvement of the marigold genotype.

The invention discloses an aqua-colchin percutaneous absorption plaster agent to treat acute gout and preparing method in medicinal preparation domain, which is characterized by the following: allocating 0. 5-1. 5 wt aqua-colchin, 3-8 wt transdermal accelerant and 1000-1500 wt pressure-sensitive adhesive; hypercritical-extracting bulb of edible tulip with carbon dioxide; getting the aqua-colchin; dispersing and refining the aqua-colchin to nanometer grade; controlling the nanometer grade grain size below 500nm. This invention can increase biological availability above 10 double, which can modify treating effect distinctively.

The invention provides a transdermal delivery ointment. The transdermal delivery ointment comprises 0.05-10wt% of colchicine, 5-45wt% of medical sterile water, 5-30wt% of a water-soluble excipient, 10-60wt% of an oil-soluble excipient, and 0.1-10wt% of a transdermal enhancer, wherein the sum of the percentages of the above components is 100wt%. The invention also relates to a preparation method of the transdermal delivery ointment. The transdermal delivery ointment can be directly used against foci, and can avoid the generation of side effects of colchicine.

The invention provides a method for doubling cone haploids. The method comprises the following steps: 1, cutting off the tips of coleoptiles of buds of corn haploids; and 2, soaking embryos of the buds of the corn haploids without the tips of coleoptiles in mixed liquid of colchicines and dimethyl sulfoxide, so as to obtain corn buts with doubled chromosome. The method for doubling cone haploids, which is provided by the invention, can remarkably improve the survival rate and maturing rate of the corn haploids, wherein the survival rate is higher than 70%, which is far higher than the survival rate of a control group which is generally lower than 50%, the maturing rate is higher than 10%, which is far higher than the maturing rate of the control group which is generally about 5%; moreover, the use amount of colchicines is 5-6 times. When applied to a haploid breeding system, the method can effectively promote the reform of the corn breeding technology to realize large-scale and engineering haploid breeding.

The invention discloses a method for doubling corn haploid by a herbicide and the special herbicide of the method. According to the method for doubling the corn haploid, the corn haploid is processed by the special herbicide to obtain corn diploid; and an active ingredient of the special herbicide is any one of the following chemical compounds: amiprophos-methl, propyzamide and trifluralin. The special herbicide consists of the active ingredient of the special herbicide, accessory ingredients and water; and the accessory ingredients consist of dimethyl sulfoxide and TWEEN-80 or dimethyl sulfoxide, TWEEN-80 and thienone. The special herbicide provided by the invention causes small environment pollution and is low in toxicity and residue and prone to degradation, and the dead rate of seedlings is 0 after the corn haploid is processed by a center dropping method with the special herbicide. The method is simple, convenient and efficient, and the doubling rate can reach 27.9%; and the doubling rate of the corn haploid processed by a bud immersion method with the special herbicide can reach 17.9%, and the dead rate of seedlings is obviously lower than that of the seedlings processed by colchicine. The method and the herbicide are suitable for large-scale operation, and can be applicable to large-scale breeding of the corn haploid.

The invention relates to a new lentinula edodes strain K48 and a breeding method thereof. The new lentinula edodes strain K48 is a new strain obtained by hybridizing a dikaryon with a mutagenized monocaryon of a lentinula edodes strain 303, and is a new strain obtained by carrying out monocaryon induction cultivation through a PDA culture medium containing colchicine and carrying out hybridization; and through a double effect of mutagenesis and hybridization, the production traits, such as yield, quality and adaptability and the like, of the new strain are greatly improved in comparison with an original strain and parent strains, so that the breeding method is a simple, practical and effective edible mushroom breeding new technology.

The invention discloses a breeding method for triploid cassava. The triploid cassava is bred through the following steps: inducing diploid cassava with chemical medicines so as to double cell chromosomes, manually cutting and separating branches of the induced diploid cassava a plurality of times so as to breed branches of totally mutated tetraploid cassava, carrying out softwood or greenwood cutting propagation on the branches so as to breed tetraploid lines, and hybridizing the tetraploid lines with diploid cassava so as to breed triploid cassava. The advantages of the invention are as follows: colchicine is utilized in the invention to induce chromosome double of cassava and goal-directed breeding is carried out; the breeding method has the characteristics of a simple process, easy operation, a high success rate, short time and greatly improved efficiency in breeding new species of cassava.

Compositions comprising a cancer drug, a continuous oral dosing schedule with a drug which binds to the colchicine site of tubulin β-subunits, and methods of treating cancer in a pediatric patient using continuous dosing schedules are disclosed.