DOCSLIB.ORG

Chlormadinone Acetate As a Possible Effective Agent for Congenital Adrenal Hyperplasia to Suppress Elevated ACTH and Antagonize Masculinization

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Chlormadinone Acetate As a Possible Effective Agent for Congenital Adrenal Hyperplasia to Suppress Elevated ACTH and Antagonize Masculinization Endocrine Journal 1995, 42(4), 505-508 Chlormadinone Acetate as a Possible Effective Agent for Congenital Adrenal Hyperplasia to Suppress Elevated ACTH and Antagonize Masculinization YUKIo KAGEYAMA, SATOSHIKITAHARA, TETSUROTSUKAMOTO, TOsHIHIKOTSUJII, SYUITIGOTO ANDHIROYUKI OSHIMA Department of Urology, Tokyo Medical and Dental University School of Medicine, Tokyo 113, Japan Abstract. We report two cases of congenital adrenal hyperplasia (CAH) in which administration of chlormadinone acetate (CMA), a substituted progestational agent for prostatic disease, suppressed ACTH hypersecretion and lowered plasma testosterone levels. Case 1 was 83-year-old male with advanced prostatic carcinoma and CAH due to 21-hydroxylase deficiency. His plasma testosterone did not decrease in spite of a bilateral orchiectomy. Case 2 was 40-year-old female with CAH due to 21- hydroxylase deficiency suffering from virilization after the cessation of cortisol supplement therapy because of her breast carcinoma. In these two cases, 'ral administration of CMA at a daily dose of 75- 100 mg suppressed ACTH and cortisol to subnormal levels and reduced testosterone levels. With the suppressive effect on ACTH excess and antiandrogenic action, CMA may be suitable for patients with CAH suffering from symptoms due to overproduced ACTH or adrenal androgen. Key words: Chlormadinone acetate , Congenital adrenal hyperplasia, ACTH suppression (Endocrine Journal 42: 505-508,1995) CHLORMADINONE acetate (17u-acetoxy-6-chlo- adrenal hyperplasia (CAH). Chlormadinone ace- ro-4,6-pregnadiene-3,20-dione; CMA), a substituted tate, administered for the prostatic carcinoma, progestational agent, has been used in the treat- suppressed hypersecretion of ACTH and lowered ment of benign prostatic hyperplasia (BPH) and plasma testosterone levels. With this experience prostatic carcinoma because of its anti-androgenic in mind, we administered CMA to a female pa- properties. In animal experiments, CMA has been tient with CAH suffering from virilization and reported to have suppressive effects on hypothala- general skin pigmentation after the cessation of cor- mo-pituitary-adrenal axis at high doses [1-4]. No tisol supplement therapy because of her breast remarkable change in adrenal function has how- carcinoma. CMA again suppressed ACTH hyper- ever been recognized during the treatment of secretion and improved her condition. We patients with prostatic disease with CMA. described these two cases and suggest that CMA A male patient with advanced prostatic carcino- may be a suitable drug for patients with CAH suf- ma, whose plasma testosterone did not decrease in fering from symptoms caused by oversecreted spite of bilateral orchiectomy, underwent hormon- adrenal androgen. al evaluation and was found to have congenital Determination of Hormonal Values Received: December 8, 1993 Accepted: April 5, 1995 Correspondence to: Dr. Yukio KAGEYAMA, Department Levels of plasma ACTH, plasma cortisol, serum of Urology, Tokyo Medical and Dental University, 1-5-45, dehydroepiandrosterone sulfate (DHEA-S), serum Yushima, Bunkyo-ku, Tokyo 113, Japan 17c -hydroxyprogesterone (17a-OHP), plasma al- 506 KAGEYAMA et al. dosterone, plasma renin activity, serum LH, serum FSH and plasma testosterone were determined by Patients radio immunoassay at Mitsubishi Yuka Bioclinical Laboratory (Tokyo). ACTH, cortisol and some oth- Case 1 er hormones were measured at least twice, on different occasions, to determine their values be- An 83-year-old male visited our clinic complain- fore and after CMA administration. ing of nocturnal urinary frequency. He had no Antibodies and kits used to determine hormon- offspring and one of his sisters had been suspect- al values were as follows: anti-ACTH monoclonal ed to have had hermaphroditism although the antibody and ACTH-I IRMA kit (Mitsubishi Yuka) precise clinical data was not available. He was for plasma ACTH; anti-hydrocortisone rabbit se- 153 cm tall, weighed 51 kg and had mild skin pig- rum and gammacoat cortisol (Baxter) for cortisol; mentation even at sites covered by clothes. Except anti-DHEA-S-Succ-BSA (rabbit) for DHEA-S; anti for the above, no obvious symptoms were recog- 17a-OHP antibody (rabbit) and DPC 17a-OHP kit nized. A standard urological examination and a for 17a-OHP; anti-aldosterone rabbit antibody and biopsy of the prostate determined our diagnosis of aldosterone RIA kit (Dynabott) for aldosterone, advanced prostatic carcinoma. Despite a bilateral anti-angiotensin antibody and renir~ RIA beads orchiectomy as a hormonal tharapy, the patient's (Dynabott) for plasma renin activity; anti-LH mon- prostatic carcinoma continued to progress and the oclonal antibody and Spac-S LH kit (Dai-ichi RI) level of his plasma testosterone remained un- for LH; and anti-testosterone antibody (rabbit) and changed. In addition, his plasma ACTH and serum DPC total testosterone kit for testosterone. DHEA-S were extremely high while his plasma cortisol levels were within normal limits (Table 1). The patient's plasma testosterone levels remained at non-castration levels in spite of serum LH being at the lower limit of the normal range for his ad- vanced age. His blood pressure was 148/78 mmHg Table 1. Basal levels of hormones and electrolytes in two cases of CAH without glucocorticoid supple- ment therapy and the effects of CMA (100 mg/day for 4 weeks) on hormones SUPPRESSION OF ACTH BY CHLORMADINONE ACETATE IN CAH 507 in the morning and bilaterally enlarged adrenal symptoms suggesting a salt loosing tendency. The glands were diagnosed from CT scans (Fig. 1). patient had received no previous treatment for From these clinical and endocrinological results, a CAH, and oral administration of CMA at the daily diagnosis of CAH due to steroid 21 hydroxylase dose of 100 mg was started as an anti-androgen deficiency was established. Although the data for therapy for prostatic carcinoma, which resulted in the accumulation of 17a-OHP or its metabolites a marked improvement of the patient's condition. was absent, the patient's electrolytes were within Initially, the improvement was regarded as the anti- normal limits and he had not experienced any androgenic activity of the agent, but the plasma levels of testosterone were also found to decrease to castration levels. The plasma ACTH and corti- sol levels also decreased to subnormal ranges while the plasma aldosterone levels remained within nor- mal limits (Table 1). The suppression of ACTH has been maintained since the initiation of CMA administration (Table 2) and the patient's prostate cancer has been managed well without progres- sion. There has been no signs or symptoms suggesting adrenal insufficiency during the entire period. Case 2 Patient 2 was a 40-year-old female. She was 144 cm tall and weighed 44.5 kg. At the age of 13 all of her siblings including herself were diagnosed as having CAH due to steroid 21-hydroxylase de- ficiency on the basis of virilization and the elevated excretion of pregnanetriol in the urine. At that time, she underwent plastic repair of the external genitalia and received glucocorticoid supplement therapy with a daily dose of 0.5 mg dexametha- sone until the age of 38, when she was found to have breast carcinoma. Following cessation of the supplement therapy, her plasma ACTH level was elevated but her plasma cortisol levels were with- in normal limits (Table 1), after a while she began suffering from acne and general pigmentation of Fig. 1. Abdominal CT scans in case 1. White arrows the skin. The oral administration of CMA at a indicate enlarged adrenal glands. Table 2. Changes of plasma ACTH and serum cortisol after CMA administration 508 KAGEYAMA et al. daily dose of 100 mg suppressed the patient's plas- that CMA has a rather weak ability to exert a sup- ma ACTH and cortisol to subnormal levels and pressive effect on the hypothalamus, which results reduced her plasma testosterone levels (Table 1) in suppression of the elevated secretion of ACTH improving her condition. The ACTH suppression in the current CAH cases but has no significant and the patient's improved condition were main- effect on a normal hypothalamo-pituitary function. tained by a daily dose of 75 mg CMA without The assumption is consistent with previous find- adrenal insufficiency (Table 2). ings that no significant elevation of LH levels has been observed during the blocking of androgen action by CMA in the treatment of prostatic carci- Discussion noma [5]. The reason for the elevated levels of plasma aldosterone in our two patients is unclear, The current cases demonstrate that CMA is ca- but might be attributable to a mild salt loosing pable of suppressing elevated secretions of ACTH tendency resulting in secondary hyperaldoster- and reducing the production of adrenal androgens onism. After CMA administration, the elevated in patient's with CAH. plasma aldosterone level became normal in case 1 CMA, like other 17a-acetoxyprogesterones such but remained high in case 2. The difference might as medroxyprogesterone acetate or cyproterone reflect the degree of deficiency of 21-hydroxylase. acetate, has caused adrenal atrophy in experimen- The principle of the medical treatment of CAH tal animals at high doses [1-4]. Although the is to supply glucocorticoids to prevent manifesta- mechanism of adrenal suppression by CMA is un- tions of adrenal insufficiency and to suppress a clear, the structural similarity between CMA and hyperactive hypothalamo-pituitary function which corticosteroids leads us to the assumption that leads to overproduction of adrenal androgens. CMA has glucocorticoid-like effects and suppress- Cyproterone acetate has been administered to some es ACTH secretion by a negative feedback patients with CAH as an anti-androgenic agent to mechanism. Some of the 17a-acetoxyprogester- antagonize virilization by overproduced adrenal ones, including cortisol and CMA, have been androgens [6, 7]. The present results indicate that reported to cause thymus involution in rats [2], CMA is a suitable agent for antagonizing viriliza- suggesting a similarity in the pharmacological ac- tion due to CAH as an anti-androgen, as well as tion in part of CMA and cortisol.
Load more

Recommended publications
  • Pp375-430-Annex 1.Qxd
    ANNEX 1 CHEMICAL AND PHYSICAL DATA ON COMPOUNDS USED IN COMBINED ESTROGEN–PROGESTOGEN CONTRACEPTIVES AND HORMONAL MENOPAUSAL THERAPY Annex 1 describes the chemical and physical data, technical products, trends in produc- tion by region and uses of estrogens and progestogens in combined estrogen–progestogen contraceptives and hormonal menopausal therapy. Estrogens and progestogens are listed separately in alphabetical order. Trade names for these compounds alone and in combination are given in Annexes 2–4. Sales are listed according to the regions designated by WHO. These are: Africa: Algeria, Angola, Benin, Botswana, Burkina Faso, Burundi, Cameroon, Cape Verde, Central African Republic, Chad, Comoros, Congo, Côte d'Ivoire, Democratic Republic of the Congo, Equatorial Guinea, Eritrea, Ethiopia, Gabon, Gambia, Ghana, Guinea, Guinea-Bissau, Kenya, Lesotho, Liberia, Madagascar, Malawi, Mali, Mauritania, Mauritius, Mozambique, Namibia, Niger, Nigeria, Rwanda, Sao Tome and Principe, Senegal, Seychelles, Sierra Leone, South Africa, Swaziland, Togo, Uganda, United Republic of Tanzania, Zambia and Zimbabwe America (North): Canada, Central America (Antigua and Barbuda, Bahamas, Barbados, Belize, Costa Rica, Cuba, Dominica, El Salvador, Grenada, Guatemala, Haiti, Honduras, Jamaica, Mexico, Nicaragua, Panama, Puerto Rico, Saint Kitts and Nevis, Saint Lucia, Saint Vincent and the Grenadines, Suriname, Trinidad and Tobago), United States of America America (South): Argentina, Bolivia, Brazil, Chile, Colombia, Dominican Republic, Ecuador, Guyana, Paraguay,
    [Show full text]
  • Canine Vascular Tissues Are Targets for Androgens, Estrogens, Progestins, and Glucocorticoids
    Canine vascular tissues are targets for androgens, estrogens, progestins, and glucocorticoids. K B Horwitz, L D Horwitz J Clin Invest. 1982;69(4):750-758. https://doi.org/10.1172/JCI110513. Research Article Sex differences and steroid hormones are known to influence the vascular system as shown by the different incidence of atherosclerosis in men and premenopausal women, or by the increased risk of cardiovascular diseases in women taking birth control pills or men taking estrogens. However, the mechanisms for these effects in vascular tissues are not known. Since steroid actions in target tissues are mediated by receptors, we have looked for cytoplasmic steroid receptor proteins in vascular tissues of dogs. We find specific saturable receptors, sedimenting at 8S on sucrose density gradients for estrogens (measured with [3H]estradiol +/- unlabeled diethylstilbestrol), androgens (measured with [3H]R1881 +/- unlabeled R1881 and triamcinolone acetonide), and glucocorticoids (measured with [3H]dexamethasone +/- unlabeled dexamethasone); they are absent for progesterone (measured with [3H]R5020 +/- unlabeled R5020 and dihydrotestosterone). Progesterone receptors can, however, be induced by 1-wk treatment of dogs with physiological estradiol concentrations (100 pg/ml serum estrogen), indicating a functional estrogen receptor. Receptor levels range from 20 to 2,000 fmol/mg DNA. They are specific for each hormone; unrelated steroids fail to complete for binding. Low dissociation constants, measured by Scatchard analyses, show that binding is of high affinity. Steroid binding sites are in the media and/or adventitia since they persist when the intima is removed. Compared with the arteries, receptor levels are reduced 80% in inferior venae cavae of […] Find the latest version: https://jci.me/110513/pdf Canine Vascular Tissues Are Targets for Androgens, Estrogens, Progestins, and Glucocorticoids KATHRYN B.
    [Show full text]
  • Combined Estrogen–Progestogen Menopausal Therapy
    COMBINED ESTROGEN–PROGESTOGEN MENOPAUSAL THERAPY Combined estrogen–progestogen menopausal therapy was considered by previous IARC Working Groups in 1998 and 2005 (IARC, 1999, 2007). Since that time, new data have become available, these have been incorporated into the Monograph, and taken into consideration in the present evaluation. 1. Exposure Data 1.1.2 Progestogens (a) Chlormadinone acetate Combined estrogen–progestogen meno- Chem. Abstr. Serv. Reg. No.: 302-22-7 pausal therapy involves the co-administration Chem. Abstr. Name: 17-(Acetyloxy)-6-chlo- of an estrogen and a progestogen to peri- or ropregna-4,6-diene-3,20-dione menopausal women. The use of estrogens with IUPAC Systematic Name: 6-Chloro-17-hy- progestogens has been recommended to prevent droxypregna-4,6-diene-3,20-dione, acetate the estrogen-associated risk of endometrial Synonyms: 17α-Acetoxy-6-chloro-4,6- cancer. Evidence from the Women’s Health pregnadiene-3,20-dione; 6-chloro-Δ6-17- Initiative (WHI) of adverse effects from the use acetoxyprogesterone; 6-chloro-Δ6-[17α] of a continuous combined estrogen–progestogen acetoxyprogesterone has affected prescribing. Patterns of exposure Structural and molecular formulae, and relative are also changing rapidly as the use of hormonal molecular mass therapy declines, the indications are restricted, O CH and the duration of the therapy is reduced (IARC, 3 C 2007). CH3 CH3 O C 1.1 Identification of the agents CH3 H O 1.1.1 Estrogens HH For Estrogens, see the Monograph on O Estrogen-only Menopausal Therapy in this Cl volume. C23H29ClO4 Relative molecular mass: 404.9 249 IARC MONOGRAPHS – 100A (b) Cyproterone acetate Structural and molecular formulae, and relative Chem.
    [Show full text]
  • Subject Index
    Subject Index absorption enhancer 166 bile acid Ill; 160 (see also permeability enhancer) binary complexes 74 acetaminophen 61, 128, 138, 143,214 bioavailability 105, 108, 145, 153, 156, 166, (see also paracetamol) 169,173,174,177,181-183 acetic acid 75 biopharmaceutics 105 acetohexaminde 119 biphenyl 73 acetone 74, 85 biphenyl acetate 169, 175, 176,208 acetylsalicylic acid 65, 66, 95,154,200 biphenyl acetic acid 169, 121 acid hydrolysis 12 biphenylacetic ester 200 adenosinediphosphate 123 bisabolol 66 adhesive tapes 187,211,212 bitter taste 127 adiabatic compressibility 6 (see also taste, unpleasant) aerosols 188 branched CDs 3, 44,157 alfaxalone 162 brexin 218 Allidex 218 bromo-benzene 48, 73 amantadine 54 buccal absorption 155 amino acids 134 buserelin acetate 183, 193,203 amorphous state 146 butylparaben 171 Amphotericin B 13,61,66 amylase 33 caboxymethylethyl-~CO 192 androsterone 42 caffeine 128 anethol129 camomile oil 89, 103, 130,213 aniline 53, 73, 74 camphor 129, 174, 186,209,213 anthracene 73 canrenone 68, 108 aroma 129 caproic acid 73 ascaridol 66, 76 capsules 155, 197,214 ascorbic acid 128,78 caraway oil 95 aspartame 128, 155 carbamazepine 119, 161 association constant 56 carbenicillin 66 atorpine 65 carbon dioxide 85 azulenol213 carmufor 66, 79, 114, 175, 192 Carthamus tinctorius 133 bandages 187,212 carvone68 barbiturate 34,117,124 catalytic effects 152 bead polymers 188 cataplasms 187,212 beclomethasone 119, 168 COPS 22, 41 bencyclane 128 COPS! 22,41 benexate 117 cephaeline 66, 70,157,202 benoxaprofen 69,123 cetylpyridinium
    [Show full text]
  • Effects of Anti-Androgen, Tzp-4238 and Chlormadinone Acetate on the Adrenal Cortex -Histo- Pathological and Immunocyto- Chemical Studies
    ACTA HISTOCHEM. CYTOCHEM. Vol. 27, No. 4, pp. 365-372, 1994 EFFECTS OF ANTI-ANDROGEN, TZP-4238 AND CHLORMADINONE ACETATE ON THE ADRENAL CORTEX -HISTO- PATHOLOGICAL AND IMMUNOCYTO- CHEMICAL STUDIES- MASANORI MURAKOSHI, RIE INADA, MASASHI TAGAWA, KAZUHIRO IIZUKA, SHUUJI MASUDA, MINORU SUZUKI, ATSUSHI MIZOKAMI* AND KEIICHI WATANABE ** Safety Research Department, Teikoku Hormone Mfg. Co. Ltd., 1604 Shimosakunobe, Takatsu-ku, Kawasaki 213, *Department of Molecular Cell Biology, University of Occupational and Environmental Health, Kitakyushu 806 and **Department of Pathology, Tokai University School of Medicine, Bohseidai, Isehara-city, Kanagawa 259-11 Received for publication May 12, 1994, in revised form July 22, 1994 and re-revised form August 24, 1994 The atrophic effects of two synthetic steroidal anti-androgens, chlormadinone acetate (CMA) and TZP-4238, on the adrenal gland of rats were investigated by histopathological and immunocytochemical procedures. Male Sprague-Dawley rats were divided into four experimental groups. Group 1 consisted of intact controls. Groups 2 and 3 received TZP-423810 mg/kg/day and CMA 50 mg/kg/day p.o., respective- ly, for 3 weeks. Group 4 received distilled water containing 2% Tween 80 instead of TZP-4238 or CMA. CMA caused marked atrophy of the adrenal gland. Histopathologically, the remarkable atrophy was observed in the adrenal cortical cells of zonae fasciculata and reticularis. Intracellular localization of glutathione-peroxidase (GSH-PO) which effectively reduces the lipid peroxides, was mainly observed in the cytoplasmic matrix (cytosol GSH-PO) near the mitochondria or lipid droplets. In ddition, immunoreactivi- ty of intramitochondrial GSH-PO (mitochondrial GSH-PO) was less than that in the controls.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2008/0161324 A1 Johansen Et Al
    US 2008O161324A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0161324 A1 Johansen et al. (43) Pub. Date: Jul. 3, 2008 (54) COMPOSITIONS AND METHODS FOR Publication Classification TREATMENT OF VRAL DISEASES (51) Int. Cl. (76) Inventors: Lisa M. Johansen, Belmont, MA A63/495 (2006.01) (US); Christopher M. Owens, A63L/35 (2006.01) Cambridge, MA (US); Christina CI2O I/68 (2006.01) Mawhinney, Jamaica Plain, MA A63L/404 (2006.01) (US); Todd W. Chappell, Boston, A63L/35 (2006.01) MA (US); Alexander T. Brown, A63/4965 (2006.01) Watertown, MA (US); Michael G. A6II 3L/21 (2006.01) Frank, Boston, MA (US); Ralf A6IP3L/20 (2006.01) Altmeyer, Singapore (SG) (52) U.S. Cl. ........ 514/255.03: 514/647; 435/6: 514/415; Correspondence Address: 514/460, 514/275: 514/529 CLARK & ELBNG LLP 101 FEDERAL STREET BOSTON, MA 02110 (57) ABSTRACT (21) Appl. No.: 11/900,893 The present invention features compositions, methods, and kits useful in the treatment of viral diseases. In certain (22) Filed: Sep. 13, 2007 embodiments, the viral disease is caused by a single stranded RNA virus, a flaviviridae virus, or a hepatic virus. In particu Related U.S. Application Data lar embodiments, the viral disease is viral hepatitis (e.g., (60) Provisional application No. 60/844,463, filed on Sep. hepatitis A, hepatitis B, hepatitis C, hepatitis D, hepatitis E). 14, 2006, provisional application No. 60/874.061, Also featured are screening methods for identification of filed on Dec. 11, 2006. novel compounds that may be used to treat a viral disease.
    [Show full text]
  • Chlormadinone Acetate
    Chlormadinone Acetate sc-211070 Material Safety Data Sheet Hazard Alert Code EXTREME HIGH MODERATE LOW Key: Section 1 - CHEMICAL PRODUCT AND COMPANY IDENTIFICATION PRODUCT NAME Chlormadinone Acetate STATEMENT OF HAZARDOUS NATURE CONSIDERED A HAZARDOUS SUBSTANCE ACCORDING TO OSHA 29 CFR 1910.1200. NFPA FLAMMABILITY1 HEALTH0 HAZARD INSTABILITY0 SUPPLIER Santa Cruz Biotechnology, Inc. 2145 Delaware Avenue Santa Cruz, California 95060 800.457.3801 or 831.457.3800 EMERGENCY ChemWatch Within the US & Canada: 877-715-9305 Outside the US & Canada: +800 2436 2255 (1-800-CHEMCALL) or call +613 9573 3112 SYNONYMS C23-H29-Cl-O4, 17-acetoxy-6-chloro-6-dehydroprogesterone, 17alpha-acetoxy-6-chloro-6-dehydroprogesterone, "17alpha-acetoxy-6-chloro-6, 7-dehydroprogesterone", "17alpha-acetoxy-6-chloro-4, 6-pregnadiene-3, 20-dione", "17alpha-acetoxy-6-chloropregna-4, 6-diene-3, 20-dione", "17-(acetyloxy)-6-chloropregna-4, 6-diene-3, 20-dione", "6-chloro-17alpha-acetoxy-4, 6-pregnadiene-3, 20-dione", "delta(sup 6)-6-chloro-17alpha-acetoxyprogesterone", "6-chloro-delta(sup 6)-17-acetoxyprogesterone", "6-chloro-delta(sup 6)-(17alpha)acetoxyprogesterone", "6-chloro- delta(sup 6)-dehydro-17-acetoxyprogesterone", 6-chloro-6-dehydro-17alpha-acetoxyprogesterone, "6-chloro- 6-dehydro-17-alpha-hydroxyprogesterone acetate", "6-chloro-17-alpha-hydroxypregna-4, 6-diene-3, 20-dione acetate", "6-chloro-17-alpha-hydroxy-delta(sup 6)-progesterone acetate", "6-chloro-delta(sup 4, 6)-pregnadiene- 17-alpha-ol-3, 20-dione-17-", acetate, "6-chloro-pregna-4, 6-dien-17-alpha-ol-3,
    [Show full text]
  • Customs Tariff - Schedule Xxi - 1
    CUSTOMS TARIFF - SCHEDULE XXI - 1 Section XXI WORKS OF ART, COLLECTORS' PIECES AND ANTIQUES Issued January 1, 2013 CUSTOMS TARIFF - SCHEDULE 99 - i Chapter 99 SPECIAL CLASSIFICATION PROVISIONS - COMMERCIAL Notes. 1. The provisions of this Chapter are not subject to the rule of specificity in General Interpretative Rule 3 (a). 2. Goods which may be classified under the provisions of Chapter 99, if also eligible for classification under the provisions of Chapter 98, shall be classified in Chapter 98. 3. Goods may be classified under a tariff item in this Chapter and be entitled to the Most-Favoured-Nation Tariff or a preferential tariff rate of customs duty under this Chapter that applies to those goods according to the tariff treatment applicable to their country of origin only after classification under a tariff item in Chapters 1 to 97 has been determined and the conditions of any Chapter 99 provision and any applicable regulations or orders in relation thereto have been met. 4. The words and expressions used in this Chapter have the same meaning as in Chapters 1 to 97. Issued January 1, 2013 99 - 1 CUSTOMS TARIFF - SCHEDULE Tariff Unit of MFN Applicable SS Description of Goods Item Meas. Tariff Preferential Tariffs 9901.00.00 Articles and materials for use in the manufacture or repair of the Free CCCT, LDCT, GPT, UST, following to be employed in commercial fishing or the commercial MT, MUST, CIAT, CT, harvesting of marine plants: CRT, IT, NT, SLT, PT, COLT, JT: Free Artificial bait; Carapace measures; Cordage, fishing lines (including marlines), rope and twine, of a circumference not exceeding 38 mm; Devices for keeping nets open; Fish hooks; Fishing nets and netting; Jiggers; Line floats; Lobster traps; Lures; Marker buoys of any material excluding wood; Net floats; Scallop drag nets; Spat collectors and collector holders; Swivels.
    [Show full text]
  • Crystallographic and Spectroscopic Study on a Known Orally Active Progestin
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by AIR Universita degli studi di Milano Accepted Manuscript Crystallographic and spectroscopic study on a known orally active progestin Patrizia Ferraboschi, Pierangela Ciuffreda, Samuele Ciceri, Paride Grisenti, Carlo Castellano, Fiorella Meneghetti PII: S0039-128X(15)00246-9 DOI: http://dx.doi.org/10.1016/j.steroids.2015.09.007 Reference: STE 7841 To appear in: Steroids Received Date: 24 April 2015 Revised Date: 10 August 2015 Accepted Date: 27 September 2015 Please cite this article as: Ferraboschi, P., Ciuffreda, P., Ciceri, S., Grisenti, P., Castellano, C., Meneghetti, F., Crystallographic and spectroscopic study on a known orally active progestin, Steroids (2015), doi: http://dx.doi.org/ 10.1016/j.steroids.2015.09.007 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Crystallographic and spectroscopic study on a known orally active progestin Patrizia Ferraboschi,a,* Pierangela Ciuffreda,b Samuele Ciceri,a Paride Grisenti,c Carlo Castellano,d and Fiorella Meneghettie aDipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, Via Saldini 50, 20133 Milano, Italy bDipartimento di Scienze Biomediche e Cliniche “Luigi Sacco”, Università degli Studi di Milano, Via G.B.
    [Show full text]
  • Action of a Novel Nonsteroidal Antiandrogen, AA560 KEIZO
    Endocrinol. Japon. 1980, 27 (1), 69-76 Action of a Novel Nonsteroidal Antiandrogen, AA560 KEIZO SHIDA1, HIDETOSHI YAMANAKA1, ATSUSHI KOYA1, KATSUMIWAKABAYASHI2, HIROSHIMORI3, KENYU SHIBATA3 ANDEIICHIRO SHIMAZAWA3 1D epartment of Urology School of Medicine, Gunma University, Maebashi, 'Hormone Assay Center, Institute of Endocrinology, Gunma University, Maebashi, 3Research Division, Teikoku Hormone Mfg. Co., Kawasaki Synopsis The antiandrogenic properties of a new nonsteroidal antiandrogens, AA560 (N- (2-chloromethyl-2-hydroxypropionyl)-3, 4, 5-trichloroaniline) were investigated. The ventral prostate, dorselateral prostate and coagulating gland weights in rats given AA560 at1-9mg/head were significantly less than those in the intact rats. The seminal vesicle weights in rats given3-9mg/head were significantly less than those of the intact group. In intact animals given daily3or9mg of AA560there were significantly increases of serum FSH, LH and testosterone concentrations. In the in vivo experiment, the pretreatment with AA560decreased the uptake of 3H-androgens in the nuclear fraction of the ventral prostate. On the other hand, a significant increase in the uptake of3H-radioactivity in the cytosol fraction was observed. It was proved by the in vitro displacement study that AA560inhibited the binding of5a-dihydrotestosterone with a receptor protein in the prostatic cytosol. An intensive effort has been directed the transfer of5a-DHT into nucleus (Belham toward the research of antiandrogens because and Neal, 1971; Mangan and Mainwaring, of usefulness of these druge in a variety of 1972). On the other hand, SK&F7690was endocrinological disorders including hirsu- reported to inhibit the cytosol receptor bin- tism, acne, male pattern baldness, benign ding to5a-DHT and the rate of 5a-DHT prostatic hypertrophy and prostatic cancer.
    [Show full text]
  • Progestins and Rat Liver : an in Vitro Study of Binding Patricia Church Brown Yale University
    Yale University EliScholar – A Digital Platform for Scholarly Publishing at Yale Yale Medicine Thesis Digital Library School of Medicine 1980 Progestins and rat liver : an in vitro study of binding Patricia Church Brown Yale University Follow this and additional works at: http://elischolar.library.yale.edu/ymtdl Recommended Citation Brown, Patricia Church, "Progestins and rat liver : an in vitro study of binding" (1980). Yale Medicine Thesis Digital Library. 2425. http://elischolar.library.yale.edu/ymtdl/2425 This Open Access Thesis is brought to you for free and open access by the School of Medicine at EliScholar – A Digital Platform for Scholarly Publishing at Yale. It has been accepted for inclusion in Yale Medicine Thesis Digital Library by an authorized administrator of EliScholar – A Digital Platform for Scholarly Publishing at Yale. For more information, please contact elischolar@yale.edu. YALE MEDICAL LIBRARY 3 9002 08627 9206 J Digitized by the Internet Archive in 2017 with funding from The National Endowment for the Humanities and the Arcadia Fund https://archive.org/details/progestinsratlivOObrow PROGESTINS AND RAT LIVER: An In Vitro Study of Binding Patricia Church Brown A Thesis Submitted to the Yale University School of Medicine in Partial Fulfillment of the Requirements for the Degree of Doctor of Medicine 1980 \\od- Lib ACKNOWLEDGEMENTS I would like to acknowledge my gratitude to the following individuals: Dr. Arnold J. Eisenfeld for his patience and constructive guidance during the preparation of this thesis. This project has introduced me to some of the methods of thought of investigative science, an introduction that should be of benefit in my future career.
    [Show full text]
  • Growth Inhibition and Increase of Insulin Receptors in Antiestrogen-Resistant T47dcohuman Breast Cancer Cells by Progestins: Implications for Endocrine Therapies1
    [CANCER RESEARCH 45,167-173, January 1985] Growth Inhibition and Increase of Insulin Receptors in Antiestrogen-resistant T47DCOHuman Breast Cancer Cells by Progestins: Implications for Endocrine Therapies1 Kathryn B. Horwitz2 and Gary R. Freidenberg3 Departments oíMedicine and Biochemistry, Biophysics, and Genetics, University of Colorado Health Sciences Center, Denver, Colorado 80262 ABSTRACT and the duration of remissions ranges from several months to 1 year or more (1, 25, 31, 33, 39, 43, 45). These results are There is renewed interest in the use of progestins to treat comparable to those obtained with antiestrogens, the most advanced breast cancer because results with these agents are common drug used for endocrine therapy (16, 39, 44). It is not comparable to those obtained with antiestrogens. However, it is known whether progestins act directly on the regressing tumors not known whether progestins inhibit the growth of breast tumor or indirectly through other hormones, (b) In support of the cells directly and independently of estradici. To study this, we hypothesis of Horwitz et al. (20), presence of PR4 may be the have used T47Dco human breast cancer cells. The progesterone single best marker for predicting both the hormone dependence receptors in these cells do not require estrogen induction, and of tumors and the disease-free survival of patients (11, 35). This this permits study of pure progestin effects without interference has led to speculation that PR-rich tumors would be especially by estradiol. We report here that, in the absence of estradici, sensitive to progestin treatment (26). (c) In small series of studies, physiological concentrations of progestins directly inhibit prolif positive responses to progestins have been obtained in tumors eration of these cells.
    [Show full text]