Natural Treatments to get rid of Gout
The body pool of urate, and hence the plasma urate concentration, is the result of a balance between production, ingestion, and excretion. The main causes of high plasma uric acid concentrations are high intake of exogenous nucleic acid in the diet and overproduction of endogenous purine. Eating less meat, seafood, and other high-purine foods (Tables 1 and 2) leads to a lower dietary intake of nucleic acids. In contrast, subjects with genetic defects that remove the usual controls on purine biosynthesis may have overwhelmingly high endogenous levels of the waste product, uric acid. The contribution of the two sources can be assessed by placing the subject on a purine-free diet for 1 week and measuring the urinary uric acid. In this way, fewer than 5 of patients with gout have been found to excrete abnormally large amounts of urate ( 3mmol day) derived from endogenous
Long thought, erroneously, to be due to high living, gout is a disease of the joints caused by an elevated concentration of uric acid in the blood and tissues. The joints become inflamed, painful, and arthritic, owing to the abnormal deposition of sodium urate crystals. The kidneys are also affected, as excess uric acid is deposited in the kidney tubules. Gout occurs predominantly in males. Its precise cause is not known, but it often involves an underexcretion of urate. A genetic deficiency of one or another enzyme of purine metabolism may also be a factor in some cases.
Purine nucleotides are degraded by a pathway in which they lose their phosphate through the action of 5'-nucleotidase (Fig. 22-45). Adenylate yields adenosine, which is deaminated to inosine by adenosine deami-nase, and inosine is hydrolyzed to hypoxanthine (its purine base) and D-ribose. Hypoxanthine is oxidized successively to xanthine and then uric acid by xanthine oxidase, a flavoenzyme with an atom of molybdenum and four iron-sulfur centers in its prosthetic group. Molecular oxygen is the electron acceptor in this complex reaction.
Plasma creatinine level, which begins to rise only if there is significant ECV depletion and developing prerenal failure. Hyperuricemia is due to a combination of enhanced proximal tubule absorption secondary to ECV contraction and competition between uric acid and diuretic secretion along the proximal tubule. Hyperuricemia is considered by some to be an independent cardiovascular risk factor, but whether this is exaggerated by diuretic therapy is open to question. Thiazide and loop diuretics may precipitate gout, but the risk can be reduced by giving allopurinol. Diuretics are also best avoided in polycythemia, both because of the increased risk of gout and of increasing blood viscosity.
The most common functional groups that inactivate free radicals are hydroxyl (eg, phenolics), sulfhydryl (eg, cysteine and glutathione) and amino (eg, uric acid, spermine, and proteins) groups (4). Phenolic compounds are the most common forms of synthetic and natural chain-breaking antioxidants in foods. Examples of naturally occurring phenolics that inhibit lipid oxidation include -tocopherol, epicatechin, ferulic acid, and carnosic acid (Fig. 1). Many of the natural antioxidants are used in foods as plant extracts such as rosemary and mixed tocopherol isomers. Synthetic phenolics approved as food additives include bu-tylated hydroxytoluene, butylated hydroxyanisole, tertiary butylhydroquinone, and propyl gallate (Fig. 2). These phenolics are effective because of their ability to inactivate free radicals and form low-energy phenolic radicals. Natural phenolic extracts are typically added to foods at concentrations
Human plasma and other biological fluids are generally rich in scavenging and chain-breaking antioxidants, including vitamin C (ascorbic acid) and 'vitamin E.' Vitamin E is the name given to a group of eight lipid-soluble tocopherols and toco-trienols. In the human diet, 7-tocopherol is the main form of vitamin E, but the predominant form in human plasma is a-tocopherol. Bilirubin, uric acid, glutathione, flavonoids, and carotenoids also have antioxidant activity and are found in cells and or plasma. Scavenging and chain-breaking anti-oxidants found in vivo are derived overall from both endogenous and exogenous sources. Cells contain, in addition, antioxidant enzymes, the SODs, glutathione peroxidase, and catalase. The transition
Proteins are first hydrolyzed into their component amino acids, followed by deamina-tion, removal of the amino group. Finally, each of the 20 amino acids is converted to either pyruvate, acetyl-CoA, or one of the other intermediates in the Krebs cycle, for further oxidation. Free amino acids are not stored in the body. Excess proteins in the diet thus must be eliminated by the mechanism just described. Deamination releases ammonia to the blood, which can be toxic and must be rapidly removed. This can be accomplished by incorporation into new amino acids or by excretion either directly as ammonia (fish), uric acid (birds and reptiles), or urea (mammals).
Increase the dosage to 500 mg bid after 1 week, then increase by 500-mg increments every 4 weeks until the uric acid level is below 6.5 mg dL. Max dose 2 g d. Contraindicated during acute attack. -Allopurinol (Zyloprim) 300 mg PO qd, may increase by 100-300 mg q2weeks. Usually initiated after the acute attack. 10. Labs CBC, SMA 7, uric acid. UA with micro. Synovial fluid for light and polarizing micrography for crystals C&S, Gram stain, glucose, protein, cell count. X-ray views of joint. 24-hour urine for uric acid.
Uric acid Uric acid Diet ingestion of high oxalate foods such as coffee, cola drinks, beer, citrus fruit, spinach, high dose vitamin C Chronic kidney infection UTI with urea-splitting bacteria (Proteus, Klebsiella, Pseudomonas species) Persistent alkaline urine (pH 7.6) Usual composition of staghorn calculi Increase urinary uric acid excretion (acidic urinary pH) secondary to diet high in purines such as organ meats, dried legumes,fish Associated with rare hereditary disorder-cystinuria uric acid
Purines and pyrimidines are chemicals that form the nucleic acids (DNA and RNA). An important purine compound is adenosine triphosphate (ATP), which is used to transfer chemical energy for processes such as biosynthesis and transport. There are several rare defects in the synthesis of purines and pyrimidines. The most common symptom of purine overproduction is gout, which arises for several reasons, often not associated with an identifiable enzyme defect but rather due to an imbalance between purine synthesis and disposal. Gout manifests when the ultimate product of purine degradation, uric acid, accumulates and crystallizes in the joints. A very dramatic disorder of purine metabolism is Lesch-Nyhan syndrome, which is due to a defect in the enzyme hypoxanthine phosphoribo-syltransferase (HPRT), resulting in defective salvage of purines and, accordingly, in an increase in the excretion of uric acid. For reasons that are still incompletely understood, a severe defect of HPRT also causes...
Gout, from the Latin gutta or drop (of evil humor), is an ancient disease that was included in Hippocrates' Aphorisms. In the first edition of his textbook, Principles and Practice of Medicine (1892), Osler defined gout as ''a nutritional disorder associated with an excess formation of uric acid.'' Today, we recognize that this definition is partly true, but that most cases of gout are not due to excess formation of uric acid but, rather, to insufficient clearance of the substance. Hyperuricemia occurs when there is too much uric acid in the blood, a condition that is generally agreed to exist when the serum or plasma uric acid exceeds the saturation point at 37 C, which is approximately 7.0mgdl-1. Hyperuricemia is a requirement for gout, but it is not always present when a patient presents with a first episode of gout, presumably because the acute deposition of uric acid in a joint reduces blood levels transiently. However, hyperuricemia is present at some point in virtually all gout...
As well as the direct effects already noted, invertebrates can alter the physical and chemical characteristics of organic resources (Swift and Boddy, 1984). For example, temperature and water relations can be altered by loss of bark due to subcortical feeding. Aeration of wood can be considerably improved by tunnelling. On the other hand, comminution provides much smaller particles more favourable to microfungi and bacteria than Basidiomycota, a potential example of ecological engineering (Jones et al., 1994). Invertebrate faeces have an entirely different chemical composition to the resources upon which they feed, for example, they are likely often to be rich in uric acid, and hence nitrogen (Krasnoshchekov and Vishnyakova, 2003).
Voluminous newspaper advertisements (sometimes one-fourth of the space), traveling doctors and pitch men with or without their slide shows, druggists, and general storekeepers proclaimed loudly and constantly the merits of various panaceas. So powerful was the influence that millions of people had come to expect, all in one remedy (at a dollar or two the bottle), certain cure for consumption, cholera morbus, dyspepsia, fevers, ague, indigestion, diseases of the liver, gout, rheumatism, dropsy, St. Vitus's dance, epilepsy, apoplexy, paralysis, greensickness, smallpox, measles, whooping cough, and syphilis (52).
The important physiological roles played by the nucleic acid precursor rNTP and dNTP molecules in humans has become apparent since the 1970s by the recognition of 28 different inborn errors of purine and pyrimidine metabolism. The spectrum of clinical manifestations ranges from fatal immunodeficiency syndromes to muscle weakness, severe neurological deficits, anemia, renal failure, gout, and urolithiasis (uric acid kidney stones).
Dietary nucleic acids are digested fully to their component nucleosides and bases, so nucleic acids are not absorbed per se into the body. The potential toxicity to humans of dietary purine bases arises principally because primates lack expression of the gene for the hepatic enzyme uricase. Excess purines are therefore converted to uric acid rather than to the extremely soluble allantoin, as in most other mammalian species. In reptiles, snakes, spiders, and birds, uric acid is the end product of the metabolism of all nitrogenous compounds, analogous to urea in mammals. The main advantage to using this insoluble end product is that there is no obligatory water loss for its excretion, as there is for urea. Consequently, uric acid can be excreted as a slurry by these animals an evolutionary adaptation enabling survival in arid environments. In contrast, in humans, excess uric acid may accumulate in the tubules of the kidney as uric acid stones or as crystals in the interstitium,...
Lesch-Nyhan syndrome (LNS) is a rare X-linked recessive disorder that typically only impacts males, whereas females act as carriers. Research has found that approximately 1 in every 380,000 births is affected, and no ethnic groups or individuals in different geographic regions are known to be at greater risk. Individuals with LNS suffer from dystonia (including hypotonia and hypertonia), spasticity of movement, speech deficits, renal disease, gout, and mental retardation. Motor impairments are severe and often restrict an individual to use of a wheelchair with necessary physical supports. In addition, motor abilities impact the ability to produce intelligible speech and perform self-care tasks independently.
Xanthine oxidoreductase (XOR) is a molybdenum-containing complex homodimeric 300-kDa cytosolic enzyme. Each subunit contains a molybdopterin cofactor, two non-identical iron-sulfur centers, and FAD (89). The enzyme has an important physiologic role in the oxidative metabolism of purines, e.g., it catalyzes the sequence of reactions that convert hypoxanthine to xanthine then to uric acid (Fig. 4.36). hypoxanthine xanthine uric acid FIGURE 4.36 Xanthine oxidase-mediated oxidation of hypoxanthine to uric acid.
Treatment of Gout Allopurinol (see Fig. 22-47), an inhibitor of xanthine oxidase, is used to treat chronic gout. Explain the biochemical basis for this treatment. Patients treated with allopurinol sometimes develop xanthine stones in the kidneys, although the incidence of kidney damage is much lower than in untreated gout. Explain this observation in the light of the following solubilities in urine uric acid, 0.15 g L xanthine, 0.05 g L and hypox-anthine, 1.4 g L.
Physiologic incompatibilities are an important aspect of the immune response to xenografts. It is likely that physiologic incompatibilities of organ function will also become important in xenografting, although at present too few functioning xenografts have survived long enough to examine this issue. It does appear that pancreatic islets from one species can regulate glucose levels satisfactorily in another species. In addition, humans have survived for many months with renal function provided by a chimpanzee kidney. On the other hand, patients with baboon livers were found to have vastly reduced blood levels of uric acid and cholesterol because of differences in hepatic physiology. Thus, it is almost certain that important physiologic incompatibilities will become apparent when it is possible to transplant complex organs across wide species differences.
Indapamide (Lozol) is the first of a new class of oral antihypertensive diuretics, the indolines. In a randomized, prospective study, 75 patients with calcium nephrolithiasis and hypercalciuria were randomly assigned to three different therapies diet and fluid, diet and fluid + indapamide 2.5 mg day, and diet and fluid + indapamide 2.5 mg day + allopurinol 300 mg day 3 , During 3 years of treatment, indapamide caused a 50 drop in urinary Ca excretion. Thus, its hypocalciuric effect was as potent as that of the thiazide diuretics. Relative supersaturations of Ca oxalate and Ca phosphate also decreased by 50 . During the treatment period, the stone rate decreased by 95 in the indapamide group (significantly better than the 64 drop in the diet and fluid group). During indapamide treatment, there were no significant changes in serum glucose, total cholesterol or triglycerides. Serum uric acid increased by 1.0 mg dl and serum K decreased by 0.4 mEq liter after 3 years of treatment with...
Cade, a doctor in the Mental Hygiene Department of Victoria, Australia, was dedicated to the belief that manic-depression was a biological, not an unconscious, psychological disorder. In the 1940s he was attempting to discover how urine toxicity levels from patients with various mental disorders differed. Cade wanted to inject guinea pigs with various concentrations of uric acid. However, uric acid is insoluble in water and difficult to inject. To resolve this problem Cade mixed uric acid with lithium. To Cade's surprise, guinea pigs injected with the lithium solution had less toxicity in their urine. The scientist next injected the animals with lithium carbonate and observed that the animals remained conscious but less active and responsive to their environment. On the basis of these findings, Cade administered a lithium salt preparation to several highly agitated manic patients. Each of the patients had a remarkable reduction in symptoms. After Dr. Cade successfully...
A chemical abnormality of bone is the deposition of abnormal elements, such as lead, which concentrates in the brain and kidneys as well. Chronic lead poisoning has been postulated as a factor in the fall of ancient Rome and in the high incidence of gout in Victorian England (lead damage to the kidneys causing decreased uric acid excretion and elevated serum uric acid levels).
In both nonruminants and ruminants, there is extensive first-pass intestinal catabolism and or utilization of the amino acids absorbed from the lumen of the small intestine, which substantially reduces their availability to extraintestinal tissues and selectively alters the patterns of amino acids in the portal vein. 3 Amino acids that enter systemic circulation may be oxidized to provide ATP and or utilized to synthesize glucose, ketone bodies, protein, urea, uric acid, and other nitrogenous substances.
During pregnancy, an increase in vascular volume, renal output (+60 ), and glomerular filtration rate (+40 ) is noted. Other than a 1-cm increase in the size of the kidneys, these changes result in an increase in the rate of filtered creatinine, urea, sodium, calcium, and uric acid (Biyani and Joyce 2002a). Hypercal-ciuria is induced by the decrease in the production of parathormone and by an increase in the 1-25 OH-D3 produced by the placenta, which is responsible for an increase in the intestinal absorption of calcium. Despite hypercalciuria and physiological hyperuricu-ria, the incidence of calculi does not rise during pregnancy, since the rate of factors inhibitory crystallization (citrate, magnesium, glycoproteins) is also higher (Biyani and Joyce 2002a Meria et al. 1995). Urine, more alkaline because of respiratory alkalosis, opposes the formation of uric acid stones despite hype-ruricuria.
Although modest overindulgence in purine-rich food by normal subjects does not precipitate gout, it can predispose to uric acid lithiasis. Uric acid stones are relatively common in countries where the consumption of nucleic acid-rich beverages and food is high and in hot climates if insufficient fluids are consumed. Health foods such as yeast tablets, Spirulina, or supplements containing nucleotides also contribute to uric acid lithiasis. A number of compounds, such as vitamin C, increase uric acid clearance and thus can precipitate urolithiasis. Perhaps not so well recognized is the uricosuric effect of a high-protein diet and the fact that purine-rich foods also predispose to renal calcium stones. This may be because many purine-rich foods, such as spinach, are equally rich in calcium oxalate. Approximately 25 of vitamin C intake is also excreted as oxalate, which can compound the problem. The solubility of uric acid is very sensitive to the pH of the urine, which in turn may be...
The aldolase A, B, and C enzymes catalyze the reversible conversion of fructose-1-diphosphate into glyceraldehyde-3-phosphate and dihydroxyacetone phosphate, and deficiencies in the A and B enzymes have been identified. Aldolase A is expressed in embryonic tissues and adult muscle. Possibly owing to the importance of this enzyme in fetal glycolysis, its deficiency results in mental retardation, short stature, hemolytic anemia, and abnormal facial appearance. There is no known treatment for aldolase A deficiency. Aldolase B is expressed in liver, kidney, and intestine, and a deficiency of this enzyme is more common and can be exhibited at first exposure to fructose during infancy or can have its onset in adulthood. Upon ingestion of fructose-containing foods, vomiting and failure to thrive are apparent. Hypoglycemia (in some cases severe), increased blood uric acid, and liver dysfunction also occur. Fortunately, this disorder can be treated effectively by completely eliminating...
The potential benefits of the lipid-lowering effects of nicotinic acid have to be considered in the light of possibly toxic effects, particularly for the liver. These may manifest as jaundice, changes in liver function tests, changes in carbohydrate tolerance, and changes in uric acid metabolism including hyper-uricemia. There may also be accompanying ultrastructural changes. Hyperuricemia may result from effects on intestinal bacteria and enzymes, and from effects on renal tubular function. Such toxic effects are especially severe if sustained release preparations of nicotinic acid are used.
The devastating effects of Lesch-Nyhan syndrome illustrate the importance of the salvage pathways. Hy-poxanthine and guanine arise constantly from the breakdown of nucleic acids. In the absence of hypoxanthine-guanine phosphoribosyltransferase, PRPP levels rise and purines are overproduced by the de novo pathway, resulting in high levels of uric acid production and goutlike damage to tissue (see below). The brain is especially dependent on the salvage pathways, and this may account for the central nervous system damage in children with Lesch-Nyhan syndrome. This syndrome is another target of early trials in gene therapy (see Box 9-2).
Humans thus have no apparent requirement for purines from the diet, and the intestinal mucosa provides an effective barrier to their uptake through a battery of enzymes that rapidly degrade purine nucleotides, nucleosides, and bases to the metabolic waste product, uric acid. This phenomenon may represent an important evolutionary development to protect the integrity of the cellular DNA or to ensure that levels of ATP do not fluctuate in concert with the dietary intake of purines. from their metabolic end products (principally uric acid). Many investigators have shown that the fate of the dietary purine moiety depends on whether it is administered in the form of DNA, RNA, mononu-cleotides, nucleosides, or bases, with some being catabolised more readily than others. When normal subjects are fed RNA, the increase in the excretion of uric acid is dramatic alongside a modest increase in plasma urate concentrations. The effect of RNA is also twice that of DNA when the increase in purines in...
Laboratory evaluation consists of hematocrit (hemoconcentration suggests preeclampsia), platelet count, protein excretion, serum creatinine, serum uric acid, serum alanine and aspartate aminotransferase concentrations (ALT, AST), and lactic acid dehydrogenase concentration (LDH).
Glycogen storage disease (GSD) type I (GSD I) (Figure 6), the most common disorder, is due to a deficiency of glucose-1-phosphatase in the liver, kidney, and intestinal mucosa. Symptoms typically occur in infancy when the frequency of feeding decreases. Profound hypoglycemia can occur progressive hepatomegaly and liver dysfunction are due to storage of glycogen. Other metabolic derangements include lactic acidaemia, which is due to increased pyruvate production increased fatty-acid synthesis causes hypertriglyceridemia and hypercholesterolemia (causing xanthomas) hyperuricemia (causing gout and renal calculi) is due to decreased renal excretion (lactate is preferentially excreted) and increased uric-acid production owing to phosphate depletion. Other long-term complications include progressive renal disease (proteinuria) and hepatocellular carcinoma. Treatment involves frequent meals and continuous nocturnal feeding (in infants) supplemental uncooked cornstarch provides exogenous...
Extracts of meat and yeast have very high purine contents but are usually eaten in small quantities. Some vegetables may provoke gout attacks by virtue of their oxalic acid content rather than that of purines, but legumes, fast-growing parts of brassicas, and asparagus tips may also have significant nucleic acid content. Fats, white flour, sugar, and fruit juices have been separated from the 'living' part of the food and so they are poor sources of nucleic acids. Table 2 provides data for specific foodstuffs, obtained from the Documenta Geigy Chemical Composition of Foodstuffs tables. The ideal diet for subjects at risk of gout or of uric acid lithiasis is no more than one meat meal per day, using only the low-purine meat and vegetables indicated. See also Ascorbic Acid Physiology, Dietary Sources and Requirements. Choline and Phosphatidylcholine. Gout.
To suck air in by expanding the rib cage. They excrete nitrogen as insoluble uric acid, further conserving water. The nervous system of reptiles is much more complex than that of amphibians. Crocodilians developed a true cerebral cortex. Placement of the legs below the body instead of at the sides allows better support and motion. Birds (class Aves) have many distinguishing characteristics other than the obvious ones of having feathers and forelimbs developed into wings. Their necks are disproportionately long. Their skeleton contains air cavities, making them strong, yet light. Their beaks lack teeth. They have a four-chambered heart and are warm-blooded. They excrete nitrogenous wastes as uric acid. Fertilization is internal and they produce eggs with a large amount of yolk. Some birds feed on insects other invertebrates, such as worms, mollusks, and crustaceans and vertebrates. About one-fifth feed on nectar. Many eat seeds. The beak is specialized for the type of feeding behavior....
The metabolic pathways of caffeine in those mammalian species that have been studied exhibit many similarities (24). The same major reactions take place demeth-ylation, oxidation at the 8-position on the xanthine ring to form uric acids, and ring cleavage between the 8- and 9-positions to form diaminouricils. AT-acetylation also occurs. The three dimethyl- and the three monomethylxanthines that can be formed are all found in human urine after caffeine ingestion along with all of the corresponding methylated uric acids. Uracils derived from caffeine, theobromine, and paraxanthine as well as large amounts of acetylated products are also present. No xanthine is formed. The human metabolic pathway is shown in Figure 4. Specie variations in the metabolic pathways of caffeine were first observed in 1900 (1). In humans, about 70 of ingested caffeine is initially converted to paraxanthine, 25 to a mixture of theobromine and theophylline, and about 5 is oxidized without demethylation to form...
Although each amino acid has its own unique catabolic pathway(s), the catabolism of all amino acids exhibits a number of common characteristics (Table 1). Their important products include glucose, ketone bodies, fatty acids, urea, uric acid, and other nitrogenous substances (Table 2). Complete oxidation of amino acids occurs only if their carbon skeletons are ultimately converted to acetyl-CoA, which is oxidized via the Krebs cycle. On a molar basis, oxidation of amino acids is less efficient for ATP production compared with fat and glucose. Gluta-mine, however, is a major fuel for rapidly dividing cells, including enterocytes, immunologically activated lymphocytes, and tumors. 1 cells (particularly in the brain). Thus, plasma levels of ammonia (primarily NH+) must be precisely regulated. Syntheses of urea (via hepatic and intestinal urea cycles) and uric acid (via hepatic purine metabolism) represent the major pathways for ammonia detoxification in mammals and birds, respectively....
Pharmacokinetics Onset of action is within approximately 30 s, with a duration of 60 to 90 s. The drug is rapidly metabolized in the blood, with a half-life less than 7 s. The primary routes of elimination are cellular uptake and simple or facilitated diffusion by a nucleoside transport system, metabolism to various by-products, and renal excretion of these metabolic products. The predominant final metabolite of adenosine is uric acid. Specific pharmacokinetic parameters such as Vd, therapeutic plasma concentrations, and clearance are difficult to assess due to the extremely short half-life of the drug.
It has been reported that affected subjects have overproduction of apo B-100. The precise molecular defect has not been elucidated, although there are already several candidate gene loci, including the LPL. The expression of this disorder may be triggered by other factors, such as overweight, hypertension, diabetes, and gout. The treatment should include diet and exercise and, if necessary, niacin, HMC CoA reductase inhibitors, or fibrates, depending on the major lipid present in excess.
Central to the effects of ethanol is the liver, in which 60-90 of ethanol metabolism occurs. Ethanol displaces many of the substrates usually metabolized in the liver. Metabolism of ethanol by ADH in the liver generates reducing equivalents. ALDH also generates NADH with conversion of acetaldehyde to acetate. The NADH NAD+ ratio is increased, with a corresponding increase in the lactate pyruvate ratio. If lactic acidosis combines with a 3-hydroxy-butyrate predominant ketoacidosis, the blood pH can fall to 7.1 and hypoglycemia may occur. Severe ketoacidosis and hypoglycemia can cause permanent brain damage. However, in general the prognosis of alcohol-induced acidosis is good. Lactic acid also reduces the renal capacity for urate excretion. Hyperuricemia is exacerbated by alcohol-induced ketosis and acetate-mediated purine generation. Hyperuricemia explains, at least in part, the clinical observation that alcohol misuse can precipitate gout.
Cyclosporine and FK506 inhibit T-cell proliferation. Nephrotoxicity is a common and usually reversible side effect manifest by elevated serum creatinine levels, hypertension, hyperkalemia, hyperuricemia, and gout. Patients are sensitive to dehydration.12 Other side effects include headache, hirsutism, gingival hyperplasia, hyperglycemia, hypomagnesemia, hypercholesterolemia, hypertriglyceridemia, hepatotoxicity, and hemolytic uremic syndrome. Unlike those of other immunosuppressive agents, blood levels of cyclosporine and FK506 can be monitored along with serum creatinine to avoid serious toxicity however, random levels are rarely helpful and dose is adjusted based on trough levels.3
Antimycobacterials may have adverse effects at therapeutic doses. Rifampin may result in gastrointestinal distress, flulike symptoms, hepatic toxicity, renal toxicity, and various dermatologic reactions. Rifampin is also noted for a nontoxic orange-red discoloration of skin, mucous membranes, urine, semen, and tears. Pyrazinamide is the most hepatotoxic of the first-line TB medications and also inhibits the excretion of urate, with acute episodes of gout possible secondary to therapy. Adverse effects of ethambutol include gastrointestinal irritation, optic neuritis, headache, behavioral changes, pruritis, and joint pain. Optic neuritis is manifested by the loss of green-red differentiation and is usually reversible with termination of therapy.
There has been a substantial change in the predominant view regarding the relationship between diet and gout. It has even been said that ''dietary considerations now play a minor role in the treatment of hyperuricemia, despite a fascinating history and abundant literature. The relationship between gout and gluttony (overindulgence of food and alcohol) dates back to ancient times. In the fifth- century bc, Hippocrates attributed gout to dietary excesses of food and wine he advised dietary restriction and reduction of alcohol consumption. Historically, the dietary management of gout has focused on two goals (i) reducing the amount of uric acid that may be deposited as crystals in joints or soft tissues, leading to the clinical syndrome of gout, and (ii) managing the disorders that occur with increased frequency among patients with gout, including diabetes mellitus, obesity, hyperlipidemia, hypertension, and atherosclerosis.
In view of the well-recognized link between insulin resistance syndrome, hyperuricemia, and gout, a diet emphasizing reduced calorie intake with moderate restriction of carbohydrates and liberalization of protein and unsaturated fat consumption has been espoused for patients with gout. Low-purine foods are often high in both carbohydrate and saturated fats these foods tend to further decrease insulin sensitivity, thereby contributing to even higher levels of insulin, glucose, triglycerides, and low-density lipo-protein cholesterol and lower high-density lipoprotein cholesterol levels, all of which result in increased risk of coronary heart disease among these patients. Conversely, a calorie-restricted, weight-reduction diet that is low in carbohydrates (40 of total calories) and relatively high in protein (approximately 120 g per-day compared to 80-90 g in the typical Western diet) and unsaturated fat content, with no limitation of purine content, has been studied and found to result...
Ureteral obstruction in the cancer patient can be caused by direct tumor compression or uric acid nephropathy during chemotherapy or may be secondary to retroperitoneal fibrosis following radiation therapy. Acute ureteral obstruction presents with flank pain similar to urolithiasis. Chronic ureteral obstruction is often painless and, if unilateral, is often only detected incidentally. Chronic bilateral ureteral obstruction eventually will cause renal failure with patients presenting with symptoms of uremia. Urinary retention at the level of the bladder is also seen in cancer patients. It can be caused by mechanical bladder outlet obstruction, brain or spinal cord metastases, or as a side effect of medications.
Primary hyperparathyroidism may present in a variety of ways. Patients may be asymptomatic and the disease may be recognized through routine screening laboratory tests. Other patients may present with severe renal or bone disease. Because calcium affects nearly every organ system, calcium dysregulation may present clinically with a multitude of signs and symptoms. The most common symptoms include fatigue, weakness, depression, arthralgia and constipation. Conditions associated with hyperparathyroidism include kidney stones, chondrocalcinosis, osteitis fibrosa cystica, osteoporosis, hypertension, gout, peptic ulcer disease and pancreatitis. Patients with excess PTH production may experience progressive loss of bone mineralization. This is manifested as subperiosteal resorption, osteoporosis and pathologic fractures. Skeletal involvement is most readily demonstrated by radiographic films.
Mucosal organisms or their breakdown products may permeate the intestinal wall if the mucosal barrier function is breached. This barrier may be compromised by many pathological states and processes. The mucosa at the tip of the villi are particularly prone to ischaemia due to the counter-current exchange mechanism of the vessels. Shunting of blood during low flow states may lead to ischaemia affecting the tips of the villi alone. Subtle mucosal damage, which is only detectable microscopically, may occur following mild ischaemia. In transient hypoperfusion or hypoxia, the mucosal injury is more pronounced during reperfusion when the oxygen supply is re-established. This is due to damage by the putative deleterious oxygen radicals which are generated mainly via the xanthine oxidase pathway. Xanthine oxidase occurs naturally as the dehydrogenase but in ischaemia it is converted by proteolysis to the oxidase form. This latter form then catalyses a reaction which utilizes oxygen to convert...
Nitrogen is constantly taken, or fixed, from the atmosphere, oxidised to a form able to be utilised by plants and some bacteria, to be subsumed into metabolic pathways, and through the various routes described above is then excreted into the environment as reduced nitrogen where it may be reoxidised by bacteria or released back into the atmosphere as nitrogen gas. These combined processes are known collectively as the nitrogen cycle. The previous discussions have referred to the release of nitrogen during degradation of proteins and nucleic acid bases, either in the form of ammonia, the ammonium ion, urea or uric acid. The fate of all these nitrogen species is to be oxidised to nitrite ion by Nitrosomas, a family of nitrifying bacteria. The nitrite ion may be reduced and released as atmospheric nitrogen, or further oxidised to nitrate by a different group of nitrifying bacteria, Nitrobacter. The process of conversion from ammonia to nitrate is sometimes found as a tertiary treatment...
Dilatation of the urinary track provide problem-free scope advancement without dilating the ureteral mea-tus beforehand (Shokeir and Mutabagani 1998 Ulvik et al. 1995 Watterson et al. 2002), which is further facilitated by continual technical improvements in equipment (such as 7.5-F rigid ureteroscopes and flexible ur-eteroscopes) (Scarpa et al. 1996 Shokeir and Mutabagani 1998). Scope progression can be observed visually, without radiological guidance and with no radiation, provided that a confirmed and experienced endosco-pist does the procedure. Although some experts do not recommend ureteroscopy during the 3rd trimester (Vest and Warden 1990), others consider this procedure possible at any time during the pregnancy (Carringer et al. 1996 Rittenberg and Bagley 1988 Watterson et al. 2002). The calculus is ideally extracted with a Dormia basket (Ulvik et al. 1995). When the calculus must be fragmented, electrohydraulic shock is not advised because it risks inducing labor (Evans and...
Even at very low doses (0-05-0-10 g), nicotinic acid often causes cutaneous flushing ( 80 ) and pruritus (50 ). Other frequently noted adverse effects are gastrointestinal symptoms (5-20 ), liver enzyme elevations (3-10 ), and uric acid increases (5-10 ). Liver enzyme elevations occur more commonly with slow-release preparations and rapid dose increases. The clinical picture of mild liver function abnormalities usually resolves with continued therapy or reduced doses.
The hallmarks of the disease are hepatomegaly, hypoglycemia, lactic acidosis, hyperuricemia, hyperlipidemia, and growth retardation. Long-term complications include short stature, osteoporosis, gout, renal disease, pulmonary hypertension, and hepatic adenomas. Virtually all females have ultrasound findings consistent with poly-cystic ovaries. 6 Hepatic adenomas develop in a significant number of patients, and malignant transformation
Within a cell, although DNA is stable throughout life, UNA is in constant equilibrium with a metabolic pool. Purines and pyrimidines may be excreted as such in the urine or be metabolized to uric acid (purines) or carbon dioxide and ammonia (pyrimidines). Uric acid in the body comes from two sources synthesis from glycine and degradation of purines. In humans, uric acid is excreted in the urine, although in most other mammals it is converted to allantoin before excretion. The normal blood level of uric acid is 4 mg 100 mL. The kidney reabsorbs much of the filtered uric acid, but the body excretes about 1 g of uric acid in 24 h. A standard reference text should be consulted for additional information on DNA, RNA, and molecular genetics.
Gout is typically an episodic monoarthritis, although polyarticular gout (involving three or more joints) occurs in approximately 10 of cases. The description of the pain of acute gout by Thomas Sydenham in the seventeenth century remains among the best More than half of patients present with podagra, and 75-90 of patients eventually develop podagra. This joint is thought to be most susceptible to gout because it is very prone to trauma and cooling, both of which reduce the solubility of uric acid. After the first MTP, acute gout most commonly involves the ankles, knees, instep, but it can also involve the wrists, elbows, and small joints of the hands and feet. Large axial joints, such as hips, shoulders, and vertebral joints, are rarely affected. Acute gout often involves a component of tenosynovitis (inflammation of tendon sheaths), and gouty cellulitis (sterile inflammation with urate crystals in the skin) and bursitis have also been described. As Sydenham stated, the onset is...
In fowl not only has a coprodeum for such storage but a separate urodeum for urine. Reverse peristalsis moves urine through the colon to facilitate indigesta segregation for ceca entry while the mucosa actively resorbs salt and water. Microbial action on ceca contents yields volatile fatty acids similar to those in the mammal's cecum colon. Fecal excreta from mammals are a combination of coarse fiber in the core, with haustrae residue appearing on the surface as nodules. Coprodeum excreta are voided from fowl as a fibrous mass covered with a uric acid white cap that accrues with urine dehydration. Ceca excreta are separately voided as a viscous mass and may be eaten by the fowl to provide considerable nutrition, particularly vitamins.
Purines are double-ringed molecules with six- and five-membered nitrogenated rings, commonly occurring examples being adenine and guanine. When metabolized, purines ultimately give rise to uric acid, which is excreted in the urine. The average excretion rate for an adult being between 400 and 600 mg over 24 H. Uric acid and sodium urate are found in the plasma and urine. They have relatively limited solubility at body pH and urine pH, and it requires only a moderate increase in uric acid levels to precipitate the deposition of urate crystals in the tissues or in the kidneys. The clinical syndrome of gout is associated with hyperuricaemia and deposition of urate in soft tissues and joints. The underlying defect is usually a combination of overproduction and increased breakdown of purines, but the cause may range from an enzyme deficiency to a hypercatabolic state.
Colchicine (from the autumn crocus Colchicium autumnale L., an alpine flower) is used to treat acute gout, but can also arrest cells in metaphase by tubulin-depolymerisation. Metaphase-cells have their chromosomes fully condensed and aligned at the equatorial plate of the cell. Thus white blood cells or amniotic cells, stimulated into mitosis by phytohaemagglutinin and
Medicinally a concoction made with dried leaves and wine was recommended as a cure for gout (which sounds like an oxymoron). Socially, garlands of the trailing stems were popular adornments for festive occasions and were prized not only for being ornamental, but also for purported aphrodisiacal effects.
Approximately 18 bursae surround the hip joint. These are derived developmentally from and are physiologically similar to synovium and tendon sheaths. As a result, they suffer from the same inflammatory afflictions which cause problems to the joint itself. Conditions that affect the bursae include traumatic inflammation, which is usually secondary to overuse or excessive pressure infections metabolic disorders such as gout and benign and malignant growths.
Not every oxidase requires or contains a coenzyme. Urate oxidase (EC 220.127.116.11) is an exception that can be explained on the basis of the chemistry of the substrate. Urate oxidase catalyzes the oxidation of uric acid into 5-hydroxyurate according to the equation in fig. 17-10A (Kahn et al., 1997). The hydroxylation of uric acid might appear to be an oxygenation, but the 5-hydroxyl group is derived from water, and O2 is converted into H2O2, so that it is a true oxidase. Uric acid oxidation has diverse metabolic roles in plant and animals.
10.5.7 xanthine oxidase and uric acid Xanthine oxidoreductase (XOR), a metalloflavoprotein, catalyzes the oxidation of the purine bases hypoxanthine and xanthine to uric acid. XOR is a site for ROS generation in the cell (128) (Figure 10.1). High levels of XOR activity resulting in ROS production has now been shown to play an important role in reperfusion injury and in congestive heart failure (129). Xanthine oxidase and its reaction product uric acid are therefore now considered to be important biomarkers for oxidative stress and cardiovascular diseases (129,130). Uric acid in urine, serum, and plasma is measured using a spectrophotometric assay based on phosphotungstic acid reagent (131) however, for improved specificity and characterization, HPLC methods have been used recently (132,133). The most popular assay method for xanthine oxidoreduc-tase involves the spectrophotometric measurement of urate production at 292 nm, using xanthine or hypoxanthine as the substrate (134). A...
G., Blaufox, D., Borhani, N. O. et al. (1987). Is thiazide-produced uric acid elevation harmful Arch. Intern. Med. 147, 645-649. 6. Messerli, F. H., Fr hlich, E. D., Dreslinski, G. R., Suarez, D. H., and Aristimuno, G. G. (1980). Serum uric acid in essential hypertension An indicator of renal vascular involvement. Ann. Intern. Med. 93,817-821. 7. Myers, A. R., Epstein, F. H., Dodge, H. J., and Mikkelsen, W. M. (1968). The relationship of serum uric acid to risk factors in coronary heart disease. Am. J. Med. 45, 520-528. 8. Persky, V. W., Dyer, A. R., Idris-Soven, E. et al. (1979). Uric acid A risk factor for coronary heart disease Circulation 59, 970-977.
Nucleic acids are a necessary component of all cells, and are found in relatively high levels in rapidly dividing cells. Thus, the nucleic acid content of yeast (around 10 of dry weight) is approximately five times greater than in the average mammalian organ. When nucleic acids are ingested, they are first attacked in the duodenum by pancreatic nuclease. The resulting nucleotides are then attacked by nucleotidases in the intestine, resulting in nucleosides and phosphate. These in turn are further degraded to purine and pyrimidine bases. The degradation of purine bases in man results in the production of uric acid. Accumulation of uric acid beyond the excretion capacity of the kidney results in the formation of crystalline deposits in the joints and soft tissues, leading to goutlike manifestations and calculi in the urinary tract. Pyrimidines are degraded to orotic acid, the accumulation of which results in liver damage. The administration of foods of microbial origin is limited by the...
Three major systems have evolved for the elimination of excess nitrogen from the body, and animals may be classified according to their major nitrogenous excretion product. Thus most fish are ammoniatelic (ammonia excretion), reptiles and birds are uricotelic (uric acid excretion), and mammals are ureotelic (urea excretion). In addition, urea excretion is seen in some teleost fish, and urea synthesis is also present in elasmobranchs (sharks and rays) where urea functions primarily in an osmotic role, not in nitrogen excretion.
Large doses of vitamin C can produce attacks of gout and nephrolithiasis in individuals with these conditions. Others may develop diarrhea and abdominal cramps, which subside with discontinuation. Megadoses of vitamin C may result in false negative guaiac testing of feces, and may give falsely elevated glucose levels on dipstick testing.
Hypoglycemia, hepatomegaly, growth retardation, proteinuria, lactic acidemia, hyperlipidemia, hyperuricemia (gout), hepatocellular carcinoma Cardiomyopathy, skeletal myopathy, cardiorespiratory failure Hypoglycemia (mild), hepatomegaly, myopathy, hyperlipidemia Hepatomegaly, cirrhosis, liver failure, myopathy
The induction of an alkaline urine also has potential beneficial clinical effects. Acetazolamide has been used in the treatment of aspirin toxicity as urinary alkalization increases the urinary excretion of salicylates. Use of this drug for this purpose, however, is not generally recommended because the systemic acidosis that develops tends to enhance the movement of aspirin into cells, potentially increasing toxicity. Although of limited clinical benefit, alkaliniza-tion of the urine with acetazolamide will also increase the solubility of uric acid and cystine. Finally, acetazolamide has potent phosphaturic effects and is a useful agent in increasing phosphate excretion in the setting of normal renal function. On the other hand, urinary alkalinization will decrease the solubility of calcium phosphate, increasing the risk for stone formation. In addition, an alkaline urine will tend to decrease urinary ammonium excretion and in patients with advanced liver disease could contribute to...
Chronic effects include persistence of a partial Fanconi syndrome for 13 years or longer, 6 interstitial nephritis, and increased uric acid levels due to increased tubular reabsorption of urate. Chronic lead toxicity has been linked with gout, hypertension, and chronic renal failure.
Freshwater fishes are hyperosmotic regulators. That means that the concentration of ions and other solutes is greater in the blood than in their surrounding water, which in most cases is very dilute. The fish will thus absorb water osmotically from their environment through all permeable epithelia such as the gills, skin, and gut. The regulatory problem is one of getting rid of the excess water and the kidney plays that important role. A large amount of urine is produced, which is dilute and contains creatine, uric acid, and some ions. The volume of urine produced must balance the quantity of water entering the body. Sodium (Na+) and chloride (Cl ) ions passively diffuse out of the body across permeable epithelia and are actively taken up, to a large extent, across the gill epithelium. Electrolyte reabsorption out of the urine takes place across the renal tubule. Na+ is actively extracted and it appears that Cl passively follows. Calcium (Ca2+), magnesium (Mg2 +), and other divalent...
Growth, feathering, egg production, shell quality, egg size, immune response, etc. A deficiency of phosphorus at any stage of life or excess calcium prior to sexual maturity leads directly to urolithiasis visceral gout caused by high urine pH. A deficiency of calcium during lay leads directly to mortality caused by calcium depletion. Poor protein nutrition over time will lead to layers with inadequate feather cover at the end of lay, resulting in nervousness and excessive mortality resulting from peckout prolapse and bacterial infections. The nutritionist should be the part of the management team who reviews flock results routinely and is kept abreast of abnormalities involving feathering, shell quality, bone strength, and mortality due to peckouts and gout.
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