Chloromycetin

By C. Jens. Brooks Institute.

Radiologically chloromycetin 500 mg with visa, advanced cases of Wilson’s disease may have cavita- tion of the putamen (122) generic chloromycetin 500mg fast delivery. However cheap 500 mg chloromycetin with amex, putaminal lesions are not specific for Wilson’s disease buy cheap chloromycetin 250mg on line. Other causes of putaminal cavitation or lesions include hypoxic ischemic damage, methanol poisoning, mitochondrial encephalo- myopathy, and wasp-sting encephalopathy. Nearly half the patients with neurological Wilson’s disease have hypodensities of the putamina on CT scans in contrast to patients with hepatic disease, who frequently have normal CT scans (123). MRI is more sensitive, and almost all patients with neurological features have some disturbance on T2-weighted images in the basal ganglia with a pattern of symmetrical, bilateral, concentric-laminar T2 hyperintensity, and the involvement of the pars compacta of the substantia nigra, periaqueductal gray matter, the pontine tegmentum, and the thalamus (124). The hepatic component of Wilson’s disease may cause increased T1 signal intensity in the globus pallidus (125). In the adult age group, the basal ganglia lesions may be different from those in the pediatric group; the putaminal lesions may not be present; the globus pallidus and substantia nigra may show increased hypointensity on T2-weighted images. Cortical and subcortical lesions may also be present with a predilection to the frontal lobe. However, rare cases of neurological Wilson’s disease may have normal MRI (126). PET scanning may show a reduction of 6- fluroudopa uptake (127). The most useful diagnostic test is serum ceruloplasmin and a 24-hour urinary copper excretion supplemented by a slit-lamp examination for KF rings. Unfortunately, not all patients with Wilson’s disease have a low ceruloplasmin level (128). Measurement of liver copper concentration makes a definitive diagnosis. Normally, it is between 50–100 mg/g of tissue, and in patients with Wilson’s disease it may be over 200 mg/g (129). Hallervorden-Spatz Disease Hallervorden-Spatz disease (HSD) is usually a disease of children, but young adults may be affected. Facial dystonia tends to be prominent, coupled with gait difficulty and postural instability. Patients may have night blindness progressing to visual loss secondary to retinitis pigmentosa. Other extrapyramidal signs include choreoathetosis and a tremor that has been poorly characterized. Cognitive problems include impairment of frontal tasks and memory disturbances. Psychiatric manifestations have been reported in HSD. CT scans in HSD Copyright 2003 by Marcel Dekker, Inc. MRI, especially using a high field strength magnet, shows decreased signal intensity in the globus pallidus with a central hyperinten- sity. We have termed it the ‘‘eye of the tiger sign’’ (130). Juvenile Huntington’s Disease This autosomal dominant neurodegenerative disorder typically presents with chorea, difficulty with gait, and cognitive problems. However, the ‘‘Westphal variant’’ of the disease affecting the young may manifest bradykinesia, tremulousness, myoclonic jerks, and occasionally seizures and cognitive disturbances (131). Eye movement abnormalities including apraxia of eye movements can be remarkable in this setting. When coupled with a lack of family history, these young patients may be confused with young- onset PD, but neuroimaging and gene testing should easily distinguish the two. Hemiparkinsonism Hemiatrophy Syndrome These patients have a longstanding hemiatrophy of the body and develop a progressive bradykinesia and dystonic movements around the age of 40 (132,133). Ipsilateral corticospinal tract signs may be found, which are not a feature of PD. Neuroimaging reveals brain asymmetry with atrophy of the contralateral hemisphere with compensatory ventricular dilatation. Regio- nal cerebral metabolic rates are diminished in the hemisphere contralateral to the clinical hemiatrophy in the putamen and the medial frontal cortex, whereas in idiopathic PD the regional cerebral metabolic rates are normal or increased contralateral to the clinically affected side (134).

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Threonine After nitrogen is removed from amino acids discount chloromycetin 500mg free shipping, the carbon skeletons are oxidized Valine Tryptophan (Fig buy chloromycetin 250 mg. Most of the carbons are converted to pyruvate discount chloromycetin 250 mg on line, intermediates of the tricar- Phenylalanine boxylic acid (TCA) cycle safe 250mg chloromycetin, or to acetyl CoA. In the liver, particularly during fasting, Methionine these carbons may be converted to glucose or to ketone bodies and released into the Histidine Arginine (not required by the adult, but blood. Other tissues then oxidize the glucose and ketone bodies. Ultimately, the car- required for growth) bons of the amino acids are converted to CO2 and H2O. Many of these digestive proteases are synthesized as larger, inactive forms known as zymogens. After zymogens are secreted into the digestive tract, they are cleaved to produce the active proteases. In the stomach, pepsin begins the digestion of proteins by hydrolyzing them to smaller polypeptides. The contents of the stomach pass into the small intestine, where enzymes produced by the exocrine pancreas act. The pancreatic proteases (trypsin, chymotrypsin, elastase, and the carboxypeptidases) cleave the polypep- tides into oligopeptides and amino acids. Further cleavage of the oligopeptides to amino acids is accomplished by enzymes produced by the intestinal epithelial cells. These enzymes include aminopeptidases located on the brush border and other peptidases located within the cells. Ultimately, the amino acids produced by protein digestion are absorbed through the intestinal epithelial cells and enter the blood. A large number of overlapping transport systems exist for amino acids in cells. Some systems contain facilitative transporters, whereas others express sodium- linked tranporters, which allow the active transport of amino acids into cells. Defects in amino acid transport can lead to disease. Proteins are also continually synthesized and degraded (turnover) in cells. A wide variety of proteases exist in cells to carry out this activity. Lysosomal pro- teases (cathepsins) degrade proteins that enter lysosomes. Cytoplasmic proteins targeted for turnover are covalently linked to the small protein ubiquitin,which then interacts with a large protein complex, the proteasome, to degrade the pro- tein in an adenosine triphosphate (ATP)-dependent process. The amino acids released from proteins during turnover can then be used for the synthesis of new proteins or for energy generation. THE WAITING ROOM Sissy Fibrosa, a young child with cystic fibrosis, has had repeated bouts of bronchitis caused by Pseudomonas aeruginosa. With each of these infections, her response to aerosolized antibiotics has been good. However, her malabsorption of food continues, resulting in foul-smelling, glistening, bulky stools. She is now in the 24th percentile for height and the 20th percentile for weight. She is often listless and irritable, and she tires easily. When her pediatrician discovered that her levels of the serum proteins 687 688 SECTION SEVEN / NITROGEN METABOLISM albumin, transferrin, and thyroid hormone binding prealbumin (transthyretin) were low to low-normal (indicating protein malnutrition), Sissy was given enteric-coated microspheres of pancreatic enzymes. Almost immediately, the character of Sissy’s Food stools became more normal and she began gaining weight. In the next 6 months, her growth curves showed improvement, and she seemed brighter, more active, and less irritable. HCl Stomach For the first few months after a painful episode of renal colic, during which Protein he passed a kidney stone (see Chapter 6), Cal Kulis had faithfully main- pepsin tained a high daily fluid intake and had taken the medication required to Pancreas increase the pH of his urine.

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Nonenzymatic Antioxidants (Free Radical Scavengers) plants (methionine with the Se replacing the sulfur) cheap 250mg chloromycetin with amex, selenocysteine from animal foods discount chloromycetin 250 mg overnight delivery, Free radical scavengers convert free radicals to a nonradical nontoxic form in and inorganic selenium buy discount chloromycetin 500 mg. Most free radical scavengers are antioxidants order 250 mg chloromycetin with visa, compounds sources can be converted to selenophos- phate. Selenophosphate reacts with a unique tRNA containing bound serine to A. COO form a selenocysteine-tRNA, which incorpo- rates selenocystiene into the appropriate CH2 Glycine protein as it is being synthesized. Se home- HN GSH + HSG ostasis in the body is controlled principally through regulation of its secretion as methy- H O 2 2 lated Se. The current dietary requirement is HS CH CH Cysteine Glutathione 2 peroxidase approximately 70 g/day for adult males and GSH HN 2H2O 55 g for females. Deficiency symptoms reflect diminished antioxidant defenses and C O GSSG include symptoms of vitamin E deficiency. CH2 Glutathione disulfide Glutamate CH2 HCNH+ 3 – COO Fig 24. Glutathione peroxidase reduces hydrogen peroxide to water. The sulfhydryl group of glutathione, which is oxidized to a disulfide, is shown in blue. Glutathione peroxidase transfer electrons from glutathione (GSH) to hydrogen peroxide. CHAPTER 24 / OXYGEN TOXICITY AND FREE RADICAL INJURY 451 H O CH3 2 2 HO 2 GSH NADP+ Glutathione Glutathione peroxidase reductase Pentose H3C Phytyl O GSSG NADPH phosphate CH + 3 H pathway 2 H O α–Tocopherol 2 LOO• Fig 24. LOOH CH3 •O that neutralize free radicals by donating a hydrogen atom (with its one electron) to the radical. Antioxidants, therefore, reduce free radicals and are themselves oxi- H C 3 Phytyl dized in the reaction. VITAMIN E CH3 Vitamin E ( -tocopherol), the most widely distributed antioxidant in nature, is a O lipid-soluble antioxidant vitamin that functions principally to protect against lipid peroxidation in membranes (see Fig. Vitamin E comprises a num- H C Phytyl 3 O ber of tocopherols that differ in their methylation pattern. Among these, - O CH3 O tocopherol is the most potent antioxidant and present in the highest amount in L our diet (Fig. Vitamin E is an efficient antioxidant and nonenzymatic terminator of free radi- H2O cal chain reactions, and has little pro-oxidant activity. When Vitamin E donates an LOOH electron to a lipid peroxy radical, it is converted to a free radical form that is stabi- lized by resonance. If this free radical form were to act as a pro-oxidant and abstract CH3 OH Phytyl an electron from a polyunsaturated lipid, it would be oxidizing that lipid and actu- O ally propagate the free radical chain reaction. The chemistry of vitamin E is such that it has a much greater tendency to donate a second electron and go to the fully H3C O oxidized form. Vitamin E ( -tocopherol) terminates Although ascorbate (vitamin C) is an oxidation-reduction coenzyme that functions free radical lipid peroxidation by donating single in collagen synthesis and other reactions, it also plays a role in free radical defense. It is water-soluble and circulates unbound in so doing, the -tocopherol is converted to the blood and extracellular fluid, where it has access to the lipid-soluble vitamin E fully oxidized tocopheryl quinone. CAROTENOIDS Vitamin E is found in the diet in the Carotenoids is a term applied to -carotene (the precursor of vitamin A) and simi- lipid fractions of some vegetable oils and in liver, egg yolks, and cereals. It lar compounds with functional oxygen-containing substituents on the rings, such as is absorbed together with lipids, and fat mal- zeaxanthin and lutein (Fig. These compounds can exert antioxidant effects, absorption results in symptomatic deficien- as well as quench singlet O2 (singlet oxygen is a highly reactive oxygen species in cies. Vitamin E circulates in the blood in which there are no unpaired electrons in the outer orbitals, but there is one orbital lipoprotein particles. Epidemiologic studies have shown a correlation between neurologic symptoms, probably because the diets high in fruits and vegetables and health benefits, leading to the hypothesis polyunsaturated lipids in myelin and other that carotenoids might slow the progression of cancer, atherosclerosis, and other membranes of the nervous system are partic- degenerative diseases by acting as chain-breaking antioxidants.

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These lipids buy 500 mg chloromycetin visa, known as essential fatty acids buy discount chloromycetin 500mg online, are required in our diet because we cannot synthesize fatty acids with these particular arrangements of double bonds buy discount chloromycetin 250mg line. The essential fatty acids -linoleic and -linolenic acid are supplied by dietary plant oils generic chloromycetin 250 mg, and eicosapentaenoic acid (EPA) and docosa- hexaenoic acid (DHA) are supplied in fish oils. They are the precursors of the eicosanoids (a set of hormone-like molecules that are secreted by cells in small quan- tities and have numerous important effects on neighboring cells). The eicosanoids include the prostaglandins, thromboxanes, leukotrienes, and other related compounds. Proteins of animal origin (milk, egg, and meat proteins) are high quality. The proteins in plant foods are generally of lower quality, which means they are low in one or more of the essential amino acids. Vegetarians may obtain adequate amounts of the essential amino acids by eating mixtures of vegetables that comple- ment each other in terms of their amino acid composition. ESSENTIAL AMINO ACIDS Different amino acids are used in the body as precursors for the synthesis of pro- teins and other nitrogen-containing compounds. Of the 20 amino acids commonly required in the body for synthesis of protein and other compounds, nine amino acids are essential in the diet of an adult human because they cannot be synthesized in the body. These are lysine, isoleucine, leucine, threonine, valine, tryptophan, pheny- Students often use mnemonics to lalanine, methionine, and histidine. Children and pregnant women have a high rate of pro- “Little TV tonight. Histidine is essential in the diet of the adult in (tryptophan) PM (phenyl- alanine-methion- very small quantities because adults efficiently recycle histidine. Tyrosine and cysteine are considered conditionally essential. Tyrosine is synthesized from phenylalanine, and it is required in the diet if phenylalanine intake is inadequate, or if an individual is congenitally deficient in an enzyme required to convert phenylalanine to tyrosine (the congenital disease phenylketonuria). Cysteine is synthesized by using sulfur from methionine, and it also may be required in the diet under certain conditions. NITROGEN BALANCE The proteins in the body undergo constant turnover; that is, they are constantly being degraded to amino acids and resynthesized. When a protein is degraded, CHAPTER 1 / METABOLIC FUELS AND DIETARY COMPONENTS 13 its amino acids are released into the pool of free amino acids in the body. Major Nitrogenous Excretion Products amino acids from dietary proteins also enter this pool. Free amino acids can have one of three fates: they are used to make proteins, they serve as precursors for synthesis of essential nitrogen-containing compounds (e. When amino acids are oxidized, their Uric acid nitrogen atoms are excreted in the urine principally in the form of urea. The urine NH 4 also contains smaller amounts of other nitrogenous excretory products (uric acid, creatinine, and NH4 ) derived from the degradation of amino acids and com- pounds synthesized from amino acids (Table 1. Some nitrogen is also lost in sweat, feces, and cells that slough off. Multiple vitamin deficiencies Nitrogen balance is the difference between the amount of nitrogen taken into accompanying malnutrition are far the body each day (mainly in the form of dietary protein) and the amount of more common in the United States nitrogen in compounds lost (Table 1. If more nitrogen is ingested than than the characteristic deficiency diseases excreted, a person is said to be in positive nitrogen balance. Positive nitrogen associated with diets lacking just one vitamin, balance occurs in growing individuals (e. Con- The characteristic deficiency diseases arising versely, if less nitrogen is ingested than excreted, a person is said to be in nega- from single vitamin deficiencies were often identified and described in humans through tive nitrogen balance. A negative nitrogen balance develops in a person who is observations of populations consuming a eating either too little protein or protein that is deficient in one or more of the restricted diet because that was all that was essential amino acids. Amino acids are continuously being mobilized from body available. If the diet is lacking an essential amino acid or if the intake of protein was discovered by a physician in Java, who is too low, new protein cannot be synthesized, and the unused amino acids will related the symptoms of beri-beri to diets be degraded, with the nitrogen appearing in the urine.

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