DOCSLIB.ORG

Methemalbumin. Ii. Effect of Pamaquine and Quinine on Pathways of Hemoglobin Metabolism

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Methemalbumin. Ii. Effect of Pamaquine and Quinine on Pathways of Hemoglobin Metabolism METHEMALBUMIN. II. EFFECT OF PAMAQUINE AND QUININE ON PATHWAYS OF HEMOGLOBIN METABOLISM William D. Blake J Clin Invest. 1948;27(3):144-150. https://doi.org/10.1172/JCI101954. Research Article Find the latest version: https://jci.me/101954/pdf METHEMALBUMIN. II. EFFECT OF PAMAQUINE AND QUININE ON PATHWAYS OF HEMOGLOBIN METABOLISM 1, 2 By WILLIAM D. BLAKE 8 (From the Department of Medicine, New York University College of Medicine, and the Research Service, Third [New York University] Medical Division, Goldwater Memorial Hospital, New York City) (Received for publication March 12, 1947) INTRODUCTION laria during the study but the period immediately fol- lowing malaria was avoided because of the questionable Methemalbuminemia has been described in as- status of certain functions of the liver (10, 11, 12). sociation with massive intravascular hemolysis Serunm bilirubin and bromsulfalein retention tests were (1, 2, 3, 4) or with limited hemolysis in the pres- normal, unless specifically mentioned. ence of liver disease (1, 5). Similarly, the in- Pamaquine naphthoate and quinine sulfate were admin- istered orally, the dosage in each case being expressed jection of large amounts of hemoglobin may result in terms of the free base. Plasma pamaquine (13) and in methemalbuminemia (1), whereas smaller quinine concentrations (14) were estimated at intervals amounts do so only in the presence of a damaged to ascertain reliability of drug intake. Pamaquine dosage liver (6). Hematin injected intravenously rapidly regimens were either 15 mg. every four hours or 10 mg. combines with serum albumin to form methemal- every eight hours. Quinine was given as the sulfate in 0.6 gram doses every eight hours. bumin (7) which is then converted to bilirubin Commercial hemin' was recrystallized (15) prior to and is largely recoverable as fecal urobilinogen being prepared for intravenous injection (8). One of five (8). patients receiving hematin suffered dizziness and ab- It has been noted that the concurrent adminis- dominal and back pain of short duration. The injection and quinine also leads to was discontinued and the patient withdrawn from the tration of pamaquine study. Uncomplicated thrombophlebitis was encountered methemalbuminemia, whereas neither drug alone following some of the slower injections. No other un- produces this effect (9). The reproducibility of toward effects were noted. the phenomenon suggested the use of these drugs Hemoglobin solution 5 for intravenous injection was as a means of investigating methemalbumin metab- received and stored in 500 cc. sterile flasks at a concen- the tration of 7.5 ± 0.5 grams per cent. More than 98 per olism. Studies were directed toward relation- cent was present as oxyhemoglobin. One of the four ship of methemalbuminemia to the degree and patients receiving hemoglobin intravenously experienced duration of hemolysis and hemoglobinemia, to the abdominal cramps, nausea and vomiting and another, disappearance rate of methemalbumin as affected transient back pain. No hyperpyrexia or other untoward by drug action, and to the possible role of liver effects were encountered. The estimation of methemalbumin concentration has function. been described in full in the preceding paper (9). Hemo- globin was estimated by the method of Evelyn (16). MATERIALS AND METHODS Serum hemoglobin was estimated on the Beckman photo- White patients with central nervous system syphilis electric spectrophotometer by a method similar to the were used as subjects. Some received therapeutic ma- one used for methemalbumin, except that optical densi- ties were recorded at 415 mnv wave-length, the absorp- 1 The work described in this paper was done under a tion maximum of oxyhemoglobin. At this wave-length, contract, recommended by the Committee on Medical after the correction blank had been subtracted, an optical Research between the Office of Scientific Research and density of 0.076 (1 cm. cell) was estimated as equivalent Development and New York University. to a hemoglobin concentration of 1.0 mg. per cent. 2 The authors express their thanks to the Malaria Serum bilirubin was estimated by the method of Study Section of the National Institute of Health for Malloy and Evelyn (17), fecal urobilinogen by a modi- editorial assistance and for arrangements in regard to the fication of Watson's method (18) yielding 90-100 per publication of this paper. They are also grateful to the cent recovery, coproporphyrin by the method of Dobriner Abbott Laboratories, E. I. du Pont de Nemours and and Rhoads (19), and bromsulfalein retention in per cent Company, Inc., E. R. Squibb and Sons, Eli Lilly and Company, Sharp and Dohme, and Wyeth, Inc., for con- 4 Eastman Kodak Company. tributing toward the publication costs. 6 Supplied through the courtesy of Dr. Robert B. 8 Captain, MC, AUS. Pennell of Sharp & Dohme, Inc. 144 PAMAQUINE-QUININE: EFFECT ON HEMOGLOBIN METABOLISM 145 by the estimation of serum bromsulfalein at five and 30 control, pamaquine, and combined pamaquine-qui- minutes after the intravenous injection of 5 mg. per kilo nine periods (Figure 1). Pamaquine dosage of body weight. was 90 mg. per day throughout in both patients. RESULTS Only during combined drug administration was Hemolysis during combined pamaquine-quinine urobilinogen output significantly increased over administration. Fecal urobilinogen excretion was the control period. A slightly increased output estimated in two individuals during successive of doubtful significance occurred during pama- quine alone in one patient. Total coproporphyrin excretion, estimated in one of the patients, also showed an increased output only during combined 20C _REP pamaquine-quinine administration (Figure 1). The administration of 400 mg. of hematin had no effect on coproporphyrin output in this individual. 100 Methemalbuminemia not a result of hemolysis CONT PAM PAM+QUIN alone. One of the patients mentioned above de- veloped methemalbuminemia on the third day of fl COPRO. combined drug administration. It was estimated nURO. from the increment in fecal urobilinogen excre- SOC0 0 G I tion that no more than 2.5 grams of hemoglobin was catabolized per day in excess of the patient's 40C ..CRAr- - control rate. A comparable amount of hemoglobin m(D r--- 2001 was administered intravenously to five patients a-6 who were receiving no drug to determine whether 300 rn _ _ _ an equivalent degree of hemolysis alone would II I produce methemalbumin. Two patients received, 0 I__n | respectively, single doses of 7.0 and 9.0 grams of Ix aoc 200- hemoglobin in one hour (Table I) and three re- 2 ceived multiple small injections of 4.5 - 6.5 grams 100 per day in divided doses for periods of two to four Tx days (Figure 2). None developed methemalbu- CONT PAM PAM + QUIN minemia. One of the latter patients subsequently I I I I 10 5 10 15 20 25 was given a large single dose of 15.0 grams of TIME IN DAYS hemoglobin. Methemalbumin was present in the FIG. 1. FECAL UROBILINOGEN AND TOTAL COPROPOR- serum of this patient at 24 hours, at which time PHYRIN ExCRETION AS AFFECTED BY THE ADMINISTRA- no free hemoglobin was demonstrable (Table I). TION OF PAMAQUINE AND COMBINED PAMAQUINE AND Methemalbuminemia following hemoglobin in- QUININE jection during pamaquine and/or quinine ad- The excretion per 24 hours of the two pigments was ministration.' Two patients were given intra- estimated during a control period (CONT), during the - a administration of 90 mg. of pamaquine base daily (PAM), venously 4.5 6.5 grams of hemoglobin day in and during the administration of 90 mg. of pamaquine divided doses for three days during pamaquine base and 1.8 gm. quinine base daily (PAM + QUIN). and for three days during quinine administration 48-96 hour stool specimens were pooled as indicated in (Figure 2), to ascertain whether either drug alone the figure. would promote methemalbumin formation if free The excretion on patient Cra was complicated by the intravenous administration of 400 mg. of hematin, as hemoglobin were available. No significant met- indicated by the arrows on the lower part of the figure. hemalbumin appeared in one patient during the The four-day period following each hematin injection pamaquine period, whereas in the other, there was includes a blocked off area which represents the uro- trace formation. Quinine caused clear-cut met- bilinogen excretion from 50 per cent of the injected hematin on the assumption that a minimum of 50 per hemalbumin formation under the same conditions cent is recoverable as fecal urobilinogen (8). of hemoglobin administration. 146 WILLIAM D. BLAKE TABLE I Serum optical density at 405 and 415 mp wave-lengths (the absorption maxima of methemalbumin and hemoglobin respectively) 24 hours after a single intravenous dose of hemoglobin Hemolysis resulting from the handling of the blood or hemoglobinemia is judged qualitatively by the shape of the absorption curve from 540 m," to 600 mr/ wave-length. Hemo- Optical density 405 mp Optical density 415 me& Serum PatientPatient glmobi __ __ ____ ____ ___ _-H mlss Methem- globid bilirubin aHemolysisnlbumi Actual Expected Difference Actual Expected Difference grams mg. % ROF 7.0 .42 .564 .565 - .001 .619 .595 + .024 0 0 KEN 9.0 .45 .669 .580 + .089 .707 .615 + .092 + 0 BRA 15.0 .47 1.860 .590 +1.270 1.683 .630 +1.053 0 +++ BRA .40 .905 .550 + .355 .895 .585 + .310 trace + + (at 48 hours) Two patients received a similar series of hemo- jected and was superimposed upon pre-existing globin injections during combined pamaquine- methemalbuminemia present as the result of pama- quinine therapy (Figure 2). Additional met- quine-quinine administration. The amount of ad- hemalbumin was formed from the hemoglobin in- ditional methemalbumin derived from the intra- venously injected hemoglobin was of the same CONTROL PAMAQUIN QUININE PAM*+ QUIA order of magnitude as that derived from hemo- globin during the administration of quinine alone. BRA UNSHAM~LRI~E AREAS - ME Disappearance rate of serum hemoglobin re- t-fo0 tt __ -To_RX lated to combined pamaquine-quinine administra- 2.
Load more

Recommended publications
  • Human Plasma and Recombinant Hemopexins: Heme Binding Revisited
    International Journal of Molecular Sciences Article Human Plasma and Recombinant Hemopexins: Heme Binding Revisited Elena Karnaukhova 1,*, Catherine Owczarek 2, Peter Schmidt 2, Dominik J. Schaer 3 and Paul W. Buehler 4,5,* 1 Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA 2 CSL Limited, Bio21 Institute, Parkville, Victoria 3010, Australia; [email protected] (C.O.); [email protected] (P.S.) 3 Division of Internal Medicine, University Hospital of Zurich, 8091 Zurich, Switzerland; [email protected] 4 Department of Pathology, The University of Maryland School of Medicine, Baltimore, MD 21201, USA 5 The Center for Blood Oxygen Transport and Hemostasis, Department of Pediatrics, The University of Maryland School of Medicine, Baltimore, MD 21201, USA * Correspondence: [email protected] (E.K.); [email protected] (P.W.B.) Abstract: Plasma hemopexin (HPX) is the key antioxidant protein of the endogenous clearance pathway that limits the deleterious effects of heme released from hemoglobin and myoglobin (the term “heme” is used in this article to denote both the ferrous and ferric forms). During intra-vascular hemolysis, heme partitioning to protein and lipid increases as the plasma concentration of HPX declines. Therefore, the development of HPX as a replacement therapy during high heme stress could be a relevant intervention for hemolytic disorders. A logical approach to enhance HPX yield involves recombinant production strategies from human cell lines. The present study focuses on a biophysical assessment of heme binding to recombinant human HPX (rhHPX) produced in the Expi293FTM (HEK293) cell system.
    [Show full text]
  • MASSHEALTH TRANSMITTAL LETTER LAB-22 July 2002 TO
    Commonwealth of Massachusetts Executive Office of Health and Human Services Division of Medical Assistance 600 Washington Street Boston, MA 02111 www.mass.gov/dma MASSHEALTH TRANSMITTAL LETTER LAB-22 July 2002 TO: Independent Clinical Laboratories Participating in MassHealth FROM: Wendy E. Warring, Commissioner RE: Independent Clinical Laboratory Manual (Laboratory HCPCS) The federal government has revised the HCFA Common Procedure Coding System (HCPCS) for MassHealth billing. This letter transmits changes for your provider manual that contain the new and revised codes. The revised Subchapter 6 is effective for dates of service on or after April 30, 2002. The codes introduced under the 2002 HCPCS code book are effective for dates of service on or after April 30, 2002. We will accept either the new or the old codes for dates of service through July 28, 2002. For dates of service on or after July 29, 2002, you must use the new codes to receive payment. If you wish to obtain a fee schedule, you may purchase Division of Health Care Finance and Policy regulations from either the Massachusetts State Bookstore or from the Division of Health Care Finance and Policy (see addresses and telephone numbers below). You must contact them first to find out the price of the publication. The Division of Health Care Finance and Policy also has the regulations available on disk. The regulation title for laboratory is 114.3 CMR 20.00: Laboratory. Massachusetts State Bookstore Division of Health Care Finance and Policy State House, Room 116 Two Boylston Street
    [Show full text]
  • Syllabus: Page 23
    The University of Texas at El Paso College of Health Sciences Clinical Laboratory Science Program CLSC 3364 Hematology II Course Outline Spring What do you see? What is in your Head? Video or audio recordings will not be permitted. Instructor M. Lorraine Torres, Ed. D, MT (ASCP) College of Health Sciences Room 423 Phone: 747-7282 E-Mail: [email protected] Office Hours TR 3:00 – 4:00 p.m., Friday 2 – 3 p.m. or by appointment Class Schedule Monday and Wednesday 11:00 – 12:30 A.M. HSCI 135 Course Description This course is a sequel to Hematology I. It will include but is not limited to the study of the white blood cells with emphasis on white cell formation and function and the etiology and treatment of white blood cell disorders. This course will also encompass an introduction to hemostasis and laboratory determination of hemostatic disorders. Prerequisite; CLSC 3356 & CLSC 3257. Topical Outline 1. Maturation series and biology of white blood cells 2. Disorders of neutrophils 3. Reactive lymphocytes and Infectious Mononucleosis 4. Acute and chronic leukemias 5. Myelodysplastic syndromes 6. Myeloproliferative disorders 7. Multiple Myeloma and related plasma cell disorders 8. Lymphomas 9. Lipid (lysosomal) storage diseased and histiosytosis 10. Hemostatic mechanisms, platelet biology 11. Coagulation pathways 12. Quantitative and qualitative vascular and platelet disorders (congenital and acquired) 13. Disorders of plasma clotting factors 14. Interaction of the fibrinolytic, coagulation and kinin systems 15. Laboratory methods REQUIRED TEXTBOOKS: same books used for Hematology I Keohane, E.M., Smith, L.J. and Walenga, J.M. 2016. Rodak’s Hematology: Clinical Principles and applications.
    [Show full text]
  • Pathological Conditions Involving Extracellular Hemoglobin
    Pathological Conditions Involving Extracellular Hemoglobin: Molecular Mechanisms, Clinical Significance, and Novel Therapeutic Opportunities for alpha(1)-Microglobulin Gram, Magnus; Allhorn, Maria; Bülow, Leif; Hansson, Stefan; Ley, David; Olsson, Martin L; Schmidtchen, Artur; Åkerström, Bo Published in: Antioxidants & Redox Signaling DOI: 10.1089/ars.2011.4282 2012 Link to publication Citation for published version (APA): Gram, M., Allhorn, M., Bülow, L., Hansson, S., Ley, D., Olsson, M. L., Schmidtchen, A., & Åkerström, B. (2012). Pathological Conditions Involving Extracellular Hemoglobin: Molecular Mechanisms, Clinical Significance, and Novel Therapeutic Opportunities for alpha(1)-Microglobulin. Antioxidants & Redox Signaling, 17(5), 813-846. https://doi.org/10.1089/ars.2011.4282 Total number of authors: 8 General rights Unless other specific re-use rights are stated the following general rights apply: Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Read more about Creative commons licenses: https://creativecommons.org/licenses/ Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
    [Show full text]
  • Study of Plasma Glycoglobulin Hemochromogens
    Proceedings of the National Academy of Sciences Vol. 68, No. 3, pp. 609-613, March 1971 Heme Binding and Transport-A Spectrophotometric Study of Plasma Glycoglobulin Hemochromogens DAVID L. DRABKIN Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pa. 19104 Communicated by Britton Chance, December 16, 1970 ABSTRACT A hitherto unreported phenomenon is the content was only 0.004-0.007 mmol/liter (or 0.04-0.07% of immediate production of the spectrum of ferrohemo- the hemoglobin content of whole blood). At this concentration chromogens (in the presence of sodium dithionite) upon the addition in vitro of hydroxyhemin (pH 7.6-7.8) to the all of the hemoglobin present was probably in the form of plasmas or sera, as well as to certain Cohn plasma protein hemoglobin-haptoglobin (11). In most cases the serum was fractions, of all mammalian species thus far examined. used directly; in some it was found desirable to dilute the This distinctive reaction is characteristic of a coordination serum 1:1 with 0.2 M phosphate buffer, pH 7.6, prior to the complex with heme iron, and is ascribed to a remarkable affinity for heme of certain plasma glycoglobulins, which addition of heme and reductant. Plasma protein fractions IV-1, include hemopexin. Spectrophotometry has permitted IV4, IV-7, and VI of most of the above species [prepared by estimations of the specific heme-binding capacity (as the alcohol-low temperature technique (12-15) and obtained ferrohemochromogen) of the plasmas, the rate of removal mainly from the Nutritional Biochemical Corp. ] were also ex- from plasma of injected heme, and the production of bile amined.
    [Show full text]
  • Dietary and Lifestyle Factors Modulate the Activity of the Endogenous
    antioxidants Article Dietary and Lifestyle Factors Modulate the Activity of the Endogenous Antioxidant System in Patients with Age-Related Macular Degeneration: Correlations with Disease Severity Zofia Ula ´nczyk 1 , Aleksandra Grabowicz 2, El˙zbietaCecerska-Hery´c 3, Daria Sleboda-Taront´ 3, El˙zbietaKrytkowska 2, Katarzyna Mozolewska-Piotrowska 2, Krzysztof Safranow 4 , Miłosz Piotr Kawa 1, Barbara Doł˛egowska 3 and Anna Machali ´nska 2,* 1 Department of General Pathology, Pomeranian Medical University, 70-111 Szczecin, Poland; zofi[email protected] (Z.U.); [email protected] (M.P.K.) 2 First Department of Ophthalmology, Pomeranian Medical University, 70-111 Szczecin, Poland; [email protected] (A.G.); [email protected] (E.K.); [email protected] (K.M.-P.) 3 Department of Laboratory Medicine, Pomeranian Medical University, 70-111 Szczecin, Poland; [email protected] (E.C.-H.); [email protected] (D.S.-T.);´ [email protected] (B.D.) 4 Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, 70-111 Szczecin, Poland; [email protected] * Correspondence: [email protected] Received: 17 August 2020; Accepted: 2 October 2020; Published: 5 October 2020 Abstract: Age-related macular degeneration (AMD) is a common cause of blindness in the elderly population, but the pathogenesis of this disease remains largely unknown. Since oxidative stress is suggested to play a major role in AMD, we aimed to assess the activity levels of components of the antioxidant system in patients with AMD. We also investigated whether lifestyle and dietary factors modulate the activity of these endogenous antioxidants and clinical parameters of disease severity.
    [Show full text]
  • The Surgical Significance of Methaemalbuminaemia
    Gut: first published as 10.1136/gut.12.12.995 on 1 December 1971. Downloaded from Gut, 1971, 12, 995-1000 The surgical significance of methaemalbuminaemia CAMERON BATTERSBY AND MARJORIE K. GREEN From the Department ofSurgery, University of Queensland, and Royal Brisbane Hospital, Brisbane, Australia SUMMARY A quantitative estimation of plasma methaemalbumin can be useful. In pancreatitis, it usually indicates severe and haemorrhagic disease, and is thus of prognostic importance, as well as indicating the need for the full therapeutic regime for conservative management of the disease. It may be helpful diagnostically in some patients with pancreatitis in whom it remains elevated after the serum amylase has returned to normal. Raised levels may indicate laparotomy in patients in whom the diagnosis of pancreatitis is con- sidered but who are not responding to conservative measures. Such patients may occasionally be suffering from intestinal infarction or other surgically remediable condition. However, it has been found that the level of methaemalbumin in the plasma may be raised above the upper limit of the normal range of 5.5 mg % in occasional cases of gastrointestinal bleeding and soft tissue trauma and is not always raised in haemorrhagic pancreatitis. Northam, Rowe, and Winstone (1963) suggested that the presence ofa raised level ofmethaemalbumin in the plasma may be helpful in the differential * Spontancotus llaeiiolysis (binds with diagnosis between haemorrhagic and oedematous * Proteolytic enzymes ho globin) http://gut.bmj.com/ pancreatitis. About the same time, a spectrometric method yielding quantitative results was described for HB-HAPTOGLOBIN| methaemalbumin estimation in plasma (Shinowara COMPLEX. and Walters, 1963) to supplement the older methods S | ~~~~~~HAEM-HAEMOPEXIN| of direct spectroscopic examination, the Schumm HAIEATIN | binds with haemnopexin COMPLEX reaction, and paper electrophoresis (Winstone, 1965).
    [Show full text]
  • Regina Qu'appelle Health Region Tests
    Regina Qu'Appelle Health Region Tests Acetaminophen Haptoglobin Alpha-Feto Protein (AFP) HbA1C AGBM Hemoglobin Electrophoresis Albumin Hemosiderin (urine) Alkaline Phosphatase (ALP) Kleihauer-Betke Test Alpha-1 Antitrypsin Lactate Alanine Aminotransferase (ALT) Luteinizing Hormone (LH) Amylase Lipid Panel (Chol, Trig, HDL, LDL ) Anti-mitochondrial antibodies Lithium Anti-RNP Liver Panel (Bili, ALT, ALP) Anti-scleroderma-70 antibodies Magnesium Anti-smooth muscle antibodies Malaria Blood Smear APTT - fresh specimen Methemalbumin Aspartate aminotransferase (AST) Microalbumin Bence Jones Protein (50-100mls 24 hour urine) Microalbumin/Creatinine Ratio Beta HCG Hypercoagulation Studies Direct Bilirubin Osmolality (Serum and Urine) Total Bilirubin Peripheral Smear review by pathologist CA-125 Phenobarbital Calcium Phenytoin (Dilantin) Carbamazepine (Tegretol) Phosphorus CBC Prolactin Carcinoembryonic Antigen (CEA) Prostate Specific Antigen (PSA) Cholinesterase w/ Dibucaine # Prothrombin Time Creatine kinase (CK) Protein Electrophoresis (PE, SPE) Creatinine (Serum and Urine) Protein Creatinine Clearance Renal Panel Cryoglobulin Reticulocyte Count Cyclosporin Sickle Cell Screen D-Dimer Sirolimus Digoxin (Lanoxin) Tacrolimus Electrolytes Theophylline Estradiol Thyroid Screen (TSH) Ferritin Tobramycin FSH Urea G-6-PD Uric Acid Gentamycin Valproic Acid (Epival, Depakene) G-Glutamyl Transferase (GGT) Vancomycin Glucose Viscosity Frozen Specimens Amikacin Factor Assays Lupus Anticoagulant Ammonia Fibrinogen Protein C Anticardiolipin Ab Heparin Assay Protein S Antiphospholipid Ab Hypercoagulation Screen Von Willebrand's Factor Anti-thrombin III H. Pylori Beta-2 Microglobulin Lactic Acid For more information refer to the RQHR Laboratory Services Manual or access the link below: RQHR Laboratory Specimen Requirements LABLisOP2002A3 RQHR Tests Laboratory Services, Regina Qu'Appelle Health Region 03/05/2016.
    [Show full text]
  • Raised Serum Concentrations of Pancreaticenzymes in Cigarette
    Gut: first published as 10.1136/gut.28.3.330 on 1 March 1987. Downloaded from Guit, 1987, 28, 330-335 Raised serum concentrations of pancreatic enzymes in cigarette smokers M A DUBICK, C N CONTEAS, H T BILLY, A P N MAJUMDAR, AND M C GEOKAS From the Enzymology Research Laboratory, Department ofMedicine, Veterans Administration Medical Center, Martinez, CA, and Departments ofMedicine and Biological Chemistry, University ofCalifornia, Davis, CA, USA SUMMARY Circulating concentrations of digestive enzymes, certain lysosomal hydrolases and protease inhibitors were measured in 19 heavy smokers and 13 non-smokers before (basal) and at 15, 30, and 60 minutes after a single intravenous injection of secretin (75 CU). In smokers, basal serum amylase and immunoreactive pancreatic elastase 2 (IRE2) concentrations were about 100% and 25% higher respectively, than in the non-smokers, whereas, no differences were observed in basal immunoreactive cationic trypsinogen (IRCT) concentrations and in acid phosphatase and f- glucuronidase activities between the two groups. Furthermore, a single injection of secretin to cigarette smokers significantly increased serum amylase, IRCT and IRE2 by 155%, 200%, and 100%, respectively when compared with their corresponding basal levels. No such increment was observed in the non-smokers. In addition, there were no significant differences in serum trypsin or elastase inhibitory capacity or immunoreactive ac,-protease inhibitor and c(2-macroglobulin levels between smokers and non-smokers. The levels and inhibitory capacity of these protease inhibitors was also not affected by secretin injection. These data suggest that cigarette smoking enhances the http://gut.bmj.com/ responsiveness of the exocrine pancreas to a physiological stimulus such as secretin, with resultant substantial increase in the concentrations of pancreatic hydrolases in blood.
    [Show full text]
  • Binding of Heme to Human Serum Albumin: Steady-State Fluorescence, Circular Dichroism and Optical Difference Spectroscopic Studi
    Indian Journal of Biochemistry & Biophysics Vol. 42, February 2005, pp. 7-12 Binding of heme to human serum albumin: Steady-state fluorescence, circular dichroism and optical difference spectroscopic studies J K Amisha Kamal † and Digambar V Behere* Department of Chemical Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400 005, India Received 17 August 2004; revised 6 December 2004 The binding of monomeric heme to human serum albumin (HSA) was investigated using steady-state fluorescence, circular dichroism (CD) and optical difference spectroscopic (ODS) techniques. The existence of one strong binding site for heme on HSA was confirmed by titrating heme with HSA and following the quenching of tryptophan (Trp214) fluorescence emission intensity that occurred due to energy transfer. Up to around 1:1 stoichiometric ratio of HSA/heme, the quenching was observed to be very strong, however at higher ratios the quenching progressed very weakly. Similarly, the negative CD band centered at ~397 nm, which appeared on adding heme to HSA, increased in intensity on sequential addition of heme up -5 to [heme]/[HSA]=1. Titration of HSA with heme was followed by ODS and the dissociation constant KD = (4.0 ±1.0) ×10 M was deduced. Results have been explained on the basis of Michaelis-Menton type of mechanism for the heme binding, in which heme first binds reversibly to His146 at the surface of the protein to form an intermediate complex, followed by irreversible binding to Tyr161 in the interior of the protein. Keywords : human serum albumin (HSA), HSA-heme, methemalbumin (MHA), steady-state fluorescence, circular dichroism, optical difference spectroscopy, two stage binding.
    [Show full text]
  • Objectives: ● to Understand the Mechanisms by Which Macrocytic Anaemia May Arise
    Objectives: ● To understand the mechanisms by which macrocytic anaemia may arise. ● To appreciate the signs and symptoms of macrocytic anaemia. ● To understand how macrocytic anaemia can be classified. ● To be able to know the causes of macrocytic anaemia. ● To understand the normal metabolism of vitamin B12 and folic acid, and to appreciate how megaloblastic anaemia may arise. ● To suggest some normoblastic causes of macrocytosis. ➢ Color Codes: ● Pink: Girls’ notes. Blue: Boys’ notes. Red: Important Notes. Gray: Extra notes. ​ ​ ​ ● Purple: Lecture notes & Pathoma notes. ➢ Done by: Samar AlOtaibi ​ ​ Rifan Hashim - Nouf AlRushaid - Kowthar Almousa - Lulu Yousef. ➢ Revised by: Abdulaziz Alshalan - Raghda Alqassim ​ ​ ​ ➢ References: - Girls&Boys Doctors Slides and Notes. - Lecture notes pathology (chapter 12) - Pathoma (chapter 5) - Team 434 & 433. ➢ Correction file: (HERE) ​ ​ ​ ➢ Check Your Understanding! (HERE) ​ ​ ​ ❖ Normal adult red cell values: Male Female Haemoglobin* (g/L) 135-175 115-155 Haematocrit(PCV)(%) packed cell ​ ​ 40-52 36-48 volume. Red cell count (x1012/L) ​ 4.5-6.5 3.9-5.6 Mean cell haemoglobin (pg) 27-34 Mean cell volume (FL) 80-95 (important) Less than 80 =microcytic,more than 95 =macrocytic Mean cell haemoglobin 300-350 concentration g/L Reticulocyte count (x109/L) ​ 25-125 (1.0-2%) ● Note that reticulocytes are directly before the mature RBCs,these reticulocytes are normal in the CBC if the bone marrow is under stress or if there is anemia. ● Other precursors are NOT normally found in CBC! ● If you find a CBC with high lymphocytic count,you MUST ask about the age of the patient because children have NORMALLY HIGH LYMPHOCYTES in blood and why is that ? because they are more prone to infection.
    [Show full text]
  • Disposal of Plasma Heme in Normal Man and Patients with Intravascular Hemolysis
    Disposal of plasma heme in normal man and patients with intravascular hemolysis David A. Sears J Clin Invest. 1970;49(1):5-14. https://doi.org/10.1172/JCI106222. Research Article The clearance of plasma protein-bound heme, its sites of removal, and the reutilization of hemeiron were studied by radioisotopic techniques in normal human subjects and in patients with intravascular hemolysis. 59 In normal subjects, injected heme- Fe was bound immediately by albumin and the β1-globulin, hemopexin. Its clearance from the plasma was descr bed by a single exponential equation, and the half-life in plasma was 7-8 hr. Removal was largely by the liver. Iron reutilization began promptly, and half the injected heme-iron was incorporated into circulating red cells within one cell life-span. In patients with intravascular hemolysis, hemopexin was depleted, and injected heme was bound solely to albumin. Plasma clearance was described by a double exponential equation of the form: y = Ae-k1t + Be-k2t. The half-lives of the two components averaged 3.9 and 22.2 hr, respectively. Removal was by the liver in at least some of the patients, and iron reutilization was variable, depending on the state of body iron stores. When hemopex'n was depleted in a normal subject by repeated heme injection, clearance mimicked that observed in the patients. Find the latest version: https://jci.me/106222/pdf Disposal of Plasma Heme in Normal Man and Patients with Intravascular Hemolysis DAVID A. SEAS From the Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14620 ABSTRACT The clearance of plasma protein-bound (4), and Fairley characterized the heme-albumin com- heme, its sites of removal, and the reutilization of heme- plex or methemalbumin (5, 6).
    [Show full text]