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Renal excretion mation of CO2 via the unstable carbonic of Ca2+ decreases purchase 30gm v-gel visa, that of Mg2+ increases 30 gm v-gel. Membrane-permeable CO2is taken Indications are hypertension buy generic v-gel 30gm line, cardiac up into the tubule cell and used to re- failure generic 30 gm v-gel with amex, and mobilization of edema 30 gm v-gel with amex. When the en- Unwanted effects of sulfonamide- zyme is inhibited, these reactions are type diuretics: (a) hypokalemia is a con- slowed, so that less Na+, HCO3– and wa- sequence of excessive K+ loss in the ter- ter are reabsorbed from the fast-flowing minal segments of the distal tubules tubular fluid. The diuretic effectiveness of CAH available for exchange with K+; (b) hy- inhibitors decreases with prolonged perglycemia and glycosuria; (c) hyper- use. CAH is also involved in the produc- uricemia—increase in serum urate lev- tion of ocular aqueous humor. Present els may precipitate gout in predisposed indications for drugs in this class in- patients. Sulfonamide diuretics com- clude: acute glaucoma, acute mountain pete with urate for the tubular organic sickness, and epilepsy. With oral administration, a strong diuresis occurs within 1 h but persists for only about 4 h. As a result, these electrolytes, together with water, are excreted in larger amounts. Diuretics 163 Normal Sulfonamide state diuretics Anion secretory Hypokalemia system Loss of+ + Uric acid Na, K H2O Thiazides Gout Na+ Cl- e. Diuretics of the sulfonamide type Lüllmann, Color Atlas of Pharmacology © 2000 Thieme All rights reserved. This diuretic effectiveness is relatively mi- response is mediated by vasopressin re- nor. At concentrations above act on the luminal membrane of tubule those required for antidiuresis, ADH cells. Both inhibit the entry of Na+, stimulates smooth musculature, includ- hence its exchange for K+ and H+. They ing that of blood vessels (“vasopres- are mostly used in combination with sin”). Blood pres- zide, because the opposing effects on K+ sure rises; coronary vasoconstriction excretion cancel each other, while the can precipitate angina pectoris. Lypres- effects on secretion of NaCl complement sin (8-L-lysine vasopressin) acts like each other. Its hor- cy), nocturnal enuresis, thrombasthe- monal effect on protein synthesis leads mia (p. The diuretic effect of spironolactone de- velops fully only with continuous ad- ministration for several days. Two pos- sible explanations are: (1) the conver- sion of spironolactone into and accumu- lation of the more slowly eliminated metabolite canrenone; (2) an inhibition of aldosterone-stimulated protein syn- thesis would become noticeable only if existing proteins had become nonfunc- tional and needed to be replaced by de novo synthesis. A particular adverse ef- fect results from interference with gon- adal hormones, as evidenced by the de- velopment of gynecomastia (enlarge- ment of male breast). Diuretics 165 Na+ K+ Triamterene Aldosterone Na+ Aldosterone + antagonists K or H+ Canrenone Protein synthesis Transport capacity Amiloride Spironolactone A. Potassium-sparing diuretics Nicotine Neuro- hypophysis Ethanol Vasoconstriction V2 Adiuretin = Vasopressin V1 H2O permeability of collecting duct Desmopressin Ornipressin Felypressin B. Antidiuretic hormone (ADH) and derivatives Lüllmann, Color Atlas of Pharmacology © 2000 Thieme All rights reserved. Because of the uptake of Na+, tion occurs when the equilibrium use of NaHCO3 must be avoided in con- between the corrosive hydrochloric acid ditions requiring restriction of NaCl in- and acid-neutralizing mucus, which take, such as hypertension, cardiac fail- forms a protective cover on the mucosal ure, and edema. Drugs are employed with the fol- Because Mg(OH)2 produces a laxative lowing therapeutic aims: (1) to relieve effect (cause: osmotic action, p. Therapeu- both) and Al(OH)3 produces constipa- tic approaches are threefold: (a) to re- tion (cause: astringent action of Al3+, p. Acting on their respective receptors, the transmitter acetylcholine, the hormone I. Drugs for Lowering Acid gastrin, and histamine released intra- Concentration mucosally stimulate the parietal cells of the gastric mucosa to increase output of Ia. Histamine comes from entero- groups such as CO32–, HCO3– or OH–, to- chromaffin-like (ECL) cells; its release is gether with their counter ions, are con- stimulated by the vagus nerve (via M1 tained in antacid drugs. With nonabsorb- antagonists that reach parietal cells via able antacids, the counter ion is dis- the blood.

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Virtually transmitted disease v-gel 30gm on line, has been shown to cause cancer of any part of the body can be affected by these types of the cervix buy 30gm v-gel. Having many sexual partners and becoming radiation order v-gel 30gm without a prescription, especially the bone marrow and the thyroid sexually active early has been shown to increase a gland generic 30gm v-gel otc. In addition generic v-gel 30gm online, it has also Additionally, being exposed to substances such as been shown that women who do not bear any children or certain chemicals, metals, or pesticides can increase the those who become pregnant late in life have an increased risk of cancer. This risk is increased even further for a smoker who is exposed to Hormone replacement therapy asbestos over a period of time. As women go through menopause, a doctor may rec- ommend hormone replacement therapy. However, progesterone is often prescribed Cancer is also a progressive disease and goes at the same time to counteract the cancerous effects of through several stages. Unfortunately, many types of cancer do not hormone replacement therapy and breast cancer as well. Early signs of cancer are often subtle and are easily mistaken for Family history signs of other less-dangerous diseases. Some types of cancers tend to occur more frequently Despite the fact that there are several hundred differ- among members of a family. In most cases, this happens ent types of cancers producing very different symptoms, by chance or due to common family habits such as ciga- the American Cancer Society has established the follow- rette smoking or excessive sun exposure. However, this ing seven symptoms as possible warning signs of cancer: can also be due to a genetic predisposition that is passed • Changes in the size, color, or shape of a wart or a mole from generation to generation. For example, if a certain • A sore that does not heal gene called BRCA1 is defective in a given family, mem- bers of that family may have an increased risk to develop • Persistent cough, hoarseness, or sore throat breast, colon, ovarian and prostate cancer. Other defec- • A lump or thickening in the breast or elsewhere tive genes have been identified that can make a person • Unusual bleeding or discharge susceptible to various types of cancer. However, it is important to have these symptoms checked There is strong evidence proving that occupational as soon as possible, especially if they do not stop. For exam- earlier a cancer is diagnosed and treated, the better the ple, asbestos workers have an increased incidence of lung chance of a cure. Similarly, bladder cancer is associated with dye, may not have any early symptoms. Therefore, it is impor- rubber, and gas workers; skin and lung cancer with tant to undergo routine screening tests, such as breast smelters, gold miners and arsenic workers; leukemia with self-exams and mammograms. Diagnosis If a person has symptoms of cancer, the doctor will Environment begin with a complete medical history and a thorough High-frequency radiation has been shown to cause physical examination. Ultra-violet radiation from the sun examined to identify any variations from the normal size, GALE ENCYCLOPEDIA OF GENETIC DISORDERS 191 KEY TERMS (CONTINUED) Magnetic resonance imaging (MRI)—A technique Nitrates/nitrites—Chemical compounds found in that employs magnetic fields and radio waves to certain foods and water that, when consumed, may create detailed images of internal body structures increase the risk of gastric cancer. Malignant—A tumor growth that spreads to another Palliative—Treatment done for relief of symptoms part of the body, usually cancerous. Mammogram—A procedure in which both breasts Pancreas—An organ located in the abdomen that are compressed/flattened and exposed to low doses secretes pancreatic juices for digestion and hor- of x rays, in an attempt to visualize the inner breast mones for maintaining blood sugar levels. Medulloblastoma—Tumor of the central nervous Pelvic examination—Physical examination per- system derived from undifferentiated cells of the formed by a physician, often associated with a Pap primitive medullary tube. Metachronous—Occurring at separate time inter- Pernicious anemia—A blood condition with vals. Peutz-Jeghers syndrome (PJS)—Inherited syndrome Metastatic cancer—A cancer that has spread to an causing polyps of the digestive tract and spots on organ or tissue from a primary cancer located else- the mouth as well as increased risk of cancer. Polyp—A mass of tissue bulging out from the nor- Multifocal breast cancer—Multiple primary can- mal surface of a mucous membrane. Primary cancer—The first or original cancer site, Mutation—A permanent change in the genetic before any metastasis. Additionally, the niques used to obtain pictures of the inside of the body doctor may order various other tests. In suspected, a special test can be done that measures the this technique, a piece of tissue is surgically removed for amount of certain substances, called tumor markers, in examination under a microscope. These proteins are mation about the cellular nature of the abnormality, the released from some types of cancer cells. Thus, the lev- stage it has reached, the aggressiveness of the cancer, and els of these substances may be abnormal when certain the extent of its spread. However, laboratory tests alone can- obtained by biopsy defines the cause of the abnormality. Since a biopsy provides the most accurate analysis, it is Blood tests are generally more useful in monitoring the considered the gold standard of diagnostic tests for cancer.

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Front end of the cell (lamellipodia): (a) Po- phosphorylates the GDP of the ADP-ribosylation fac- lymerization of actin monomers is achieved tor (ARF) to GTP! ARF-GTP are propelled forward with the help of plasma complexes then anchor on the membrane and bind membrane-based myosin I (fueled by ATP); with coatomer (! The membranes (b)reinsertion of the vesicles in the cell mem- of the vesicles contain v-SNAREs (vesicle synapto- brane; (c) uptake of ions and fluids from the some-associatedproteinreceptors) buy 30gm v-gel free shipping,whichrecognize environment discount 30gm v-gel with mastercard. This results in volved in cytosis are conveyed from front to cleavage of ARF-GTP v-gel 30gm with amex, dissociation of ARF-GDP and back buy 30gm v-gel mastercard, as on a track chain 30gm v-gel free shipping. Since the cell mem- coatomer molecules and, ultimately, to membrane brane is attached to the stable surface (pri- fusionandexocytosis(! D4,D5)totheextracellular marily fibronectin of the extracellular matrix space (ECS). This is achieved such as proteins and hormones by endocytosis with the aid of specific receptors, such as fi- on one side of the cell, and their release on the bronectin receptors in the case of fibroblasts. This is useful for transcellular transport of the macromolecules across cell lay- ers such as endothelia. Cell Migration Most cells in the body are theoretically able to move from one place to another or migrate (! By waving 30 their whip-like tail, the sperm can travel at Despopoulos, Color Atlas of Physiology © 2003 Thieme All rights reserved. Constitutive exozytosis Trans-Golgi network 1 Activation of ARF v-SNARE GNRP GTP GDP GTP GDP ARF-GTP (active) ARF-GDP 2 Coating (inactive) 3 Coatomer-coated vesicle ARF-GDP (inactive) Pi 4 Membrane fusion 5 Exocytosis Coatomer t-SNARE Plasma membrane ECS E. Cell migration K+,Cl– + – 1 K,Cl Lamellipodium Cell Support Attachment See2 points (After A. Electrical Membrane Potentials and At equilibrium potential, the chemical gradient will drive just as many ions of species Ion Channels X in the one direction as the electrical poten- An electrical potential difference occurs due to tial does in the opposite direction. The electro- the net movement of charge during ion trans- chemical potential (Em–E )x or so-called elec- port. A diffusion potential develops for in- trochemical driving “force”, will equal zero, stance, when ions (e. The rising diffusion potential then tion-dependent variable, is generally used to drives the ions back into the cell (potential- describe the permeability of a cell membrane driven ion transport;! Outward K+ dif- to a given ion instead of the permeability fusion persists until equilibrium is reached. In other words, the sum of area, gx is expressed in siemens (S = 1/Ω) per the two or the electrochemical gradient (and m2(! The equilibrium potential (E )x for any spe- Ix will therefore differ from zero when the pre- cies of ion X distributed inside (i) and outside vailingmembranepotential,Em,doesnotequal (o) a cell can be calculated using the Nernst the equilibrium potential, E. This occurs, forx equation: example, after strong transient activation of Na -K+ +-ATPase (electrogenic;! If the membrane is per- (310"K in the body), F is the Faraday constant meable to different ion species, the total con- orchargepermol(=9. It is some- times helpful to convert ln([X] /[X])o i into The membrane potential, Em, can be deter- –ln([X]/[X] ),i o V into mV and ln into log be- mined if the fractional conductances and equi- fore calculating the equilibrium potential librium potentials of the conducted ions are (! Assuming K, Na, and Cl+ + – Nernst equation then becomes are the ions in question, 1 [X]i Em! Electrochemical potential (Em– EK) and ionic currents [K]o= [K]i= Nernst equation 4. Single-channel recoprding (patch-clamp technique) 3 Data analysis 1 Experimental set-up 2 Electrode 1 Measuring unit 0 Pipette solution: –50 –25 0 –25 150mmol/l NaCl Voltage (mV) + 5mmol/l KCl Oscillograph 200ms Clamp voltage 20mV Pipette pA Burst 2 0 K+channel Clamp voltage 0mV Cytosolic 2 side Membrane patch 0 Clamp voltage –20mV Bath solution: 2 5 mmol/l NaCl +150 mmol/l KCl 0 2µm Clamp voltage –40mV 2 2 Single-channel current recording 0 3333 (After R. In single- Na+influxislowbecausethegNaandfNaofrest- channel recording, the membrane potential is ing cells are relatively small. Thisper- sodium current, INa, can rise tremendously mits the measurement of ionic current in a when large numbers of Na+ channels open single channel. The potential produced by of the I/V curve corresponds to the conduct- the transport of one ion species can also drive ance of the channel for the respective ion spe- other cations or anions through the cell mem- cies (see Eq. The K diffusion potential leads to the ef-+ intercepts the x-axis of the curve (I = 0).

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