Ebook: Purine Metabolism in Man—II: Physiology, Pharmacology, and Clinical Aspects

The study of gouty arthritis has provided a common meeting ground for the research interests of both the basic scientist and the clinician. The interest of the chemist in gout began 1776 with the isolation of uric acid from a concretion of the urinary tract by the Swedish chemist SCHEELE. The same substance was subsequently extracted from a gouty tophus by the British chemist WOLLASTONE in 1797 and a half century later the cause of the deposits of sodium urate In such tophi was traced to a hyperuricemia in the serum of gouty patients by the British physician Alfred Baring GARROD who had also received training in the chemical laboratory and was therefore a fore-runner of many of today's clinician-investigators. The recent surge of progress in understanding of some of the causes of gout in terms of specific enzyme defects marks the entrance of the biochemist into this field of investigation. The identification of the first primary defect of purine metabolism associated with over-production of uric acid, a severe or partial deficiency of the enzyme hypoxanthine-guanine phospho­ ribosyl transferase was achieved less than a decade ago. The knowledge of the mechanism of purine over-production that it generated led shortly to the identification of families carrying a dominantly (possibly X-linked) inherited increase in the activity of the enzyme phosphoribosylpyrophosphate synthetase as a cause of purine over-production. Yet this is only a start as these two types of enzyme defects account for less than five per cent of gouty patients.

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Content:
Front Matter....Pages i-xxii
Renal Handling of Uric Acid....Pages 1-22
The Effect of Urine Flow Rate on Urate Clearance....Pages 23-29
Effects of Vitamins on the Renal Handling of Uric Acid....Pages 30-35
The Uricosuric Action of Amino Acids in Man....Pages 36-40
Urate Excretion in Normal and Gouty Men....Pages 41-45
The Effect of Acid Loading on Renal Excretion of Uric Acid and Ammonium in Gout....Pages 46-55
Evidence for Two Secretory Mechanisms for Organic Acid Transport in Man....Pages 56-62
Classification of Uricosuric States Based upon Response to Pharmacologic Inhibitors of Urate Transport....Pages 63-71
Familial Renal Hypouricemia due to Isolated Tubular Defect....Pages 72-76
Isolation and Characterization of Uricine....Pages 77-80
Uricine — Uric Acid Interactions....Pages 81-85
Urinary Excretion of Uricine....Pages 86-89
Sites of Urate Transport in the Rat Nephron....Pages 90-99
Factors Affecting Urate Reabsorption in the Rat Kidney....Pages 100-109
Some Characteristics of Uric Acid Uptake by Separated Renal Tubules of the Rabbit....Pages 110-113
Effects of Drugs on the Uptake of Uric Acid by Separated Renal Tubules of the Rabbit....Pages 114-116
Tubular Handling of Allantoin in the Rat Kidney....Pages 117-121
Control of Net Cellular Uptake of Adenosine from the Lumen Side of the Guinea Pig Jejunal Epithelium....Pages 122-130
Uptake of Hypoxanthine in Human Erythrocytes....Pages 131-138
Incorporation of Purine Bases by Intact Red Blood Cells....Pages 139-150
Uric Acid Transport Characteristics in Human Erythrocytes....Pages 151-158
A Relationship between Free Urate, Protein-Bound Urate, Hyperuricemia and Gout in Caucasians and Maoris....Pages 159-162
Influence of Allopurinol on the Genetic Materials of Ehrlich Ascites Tumor Cells....Pages 163-169
6-Azauridine, an Inhibitor of the Purine Salvage Pathway....Pages 170-175
Suppression of Experimental Urate Nephropathy by Salicylate....Pages 176-178
Physiological Characteristics of Various Experimental Models for the Study of Disorders in Purine Metabolism....Pages 179-188
In Vitro Investigations on the Influence of Antirheumatic Drugs on Purine Phosphoribosyltransferases and Their Possible Clinical Consequence....Pages 189-194
Influence of Urate on Connective Tissue Metabolism....Pages 195-200
Protein Binding to Monosodium Urate Crystals and its Effect on Platelet Degranulation....Pages 201-208
Protein Adsorption to Monosodium Urate Crystals: Differential Responses of Human Peripheral Blood Neutrophils....Pages 209-213
Serum Uric Acid Levels in England and Scotland....Pages 214-222
Gout Disease. Its Natural History Based on 1,000 Observations....Pages 223-230
Hyperuricemia as a Risk Factor in Coronary Heart Disease....Pages 231-237
Hyperuricemia and other Cardiovascular Risk Factors....Pages 238-244
Recurrent Gouty Phlebitis without Articular Gout....Pages 245-248
Alterations of Human Purine Metabolism in Megaloblastic Anemia....Pages 249-255
Typing of Uric Acid Level in Cerebrospinal Fluid in Neurological and Psychiatric Diseases....Pages 256-258
Renal Tubular Transport of Urate in Fanconi Syndrome....Pages 259-265
Nutritional State and Purine Metabolism....Pages 266-268
The Effect of Different Purines and Pyrimidines on Human Pyrimidine Biosynthesis....Pages 269-273
The Effect of Weight Loss on Plasma and Urinary Uric Acid and Lipid Levels....Pages 274-277
Pathogenesis of “Fasting Hyperuricemia” and its Prophylaxis....Pages 278-287
The Treatment of Acute Gouty Arthritis....Pages 288-289
Multi-Centre Trial of Naproxen and Phenylbutazone in Acute Gout....Pages 290-296
The Influence of Allopurinol in Customary and in Slow Release Preparation on Different Parameters of Purine and Pyrimidine Metabolism....Pages 297-303
Purine Excretion in Complete Adenine Phosphoribosyltransferase Deficiency: Effect of Diet and Allopurinol Therapy....Pages 304-311
Thiopurinol: Dose-Related Effect on Urinary Oxypurine Excretion....Pages 312-319
Dose-Response Relationship of a Uricosuric Diuretic....Pages 320-327
The Pharmacology of the Hypouricemic Effect of Benzbromarone....Pages 328-333
The Metabolic Effects of Tienilic Acid, a New Diuretic with Uricosuric Properties in Man and Dog....Pages 334-341
Panel Discussion: Hyperuricemia as a Risk Factor....Pages 342-364
Back Matter....Pages 365-373

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Content:
Front Matter....Pages i-xxii
Renal Handling of Uric Acid....Pages 1-22
The Effect of Urine Flow Rate on Urate Clearance....Pages 23-29
Effects of Vitamins on the Renal Handling of Uric Acid....Pages 30-35
The Uricosuric Action of Amino Acids in Man....Pages 36-40
Urate Excretion in Normal and Gouty Men....Pages 41-45
The Effect of Acid Loading on Renal Excretion of Uric Acid and Ammonium in Gout....Pages 46-55
Evidence for Two Secretory Mechanisms for Organic Acid Transport in Man....Pages 56-62
Classification of Uricosuric States Based upon Response to Pharmacologic Inhibitors of Urate Transport....Pages 63-71
Familial Renal Hypouricemia due to Isolated Tubular Defect....Pages 72-76
Isolation and Characterization of Uricine....Pages 77-80
Uricine — Uric Acid Interactions....Pages 81-85
Urinary Excretion of Uricine....Pages 86-89
Sites of Urate Transport in the Rat Nephron....Pages 90-99
Factors Affecting Urate Reabsorption in the Rat Kidney....Pages 100-109
Some Characteristics of Uric Acid Uptake by Separated Renal Tubules of the Rabbit....Pages 110-113
Effects of Drugs on the Uptake of Uric Acid by Separated Renal Tubules of the Rabbit....Pages 114-116
Tubular Handling of Allantoin in the Rat Kidney....Pages 117-121
Control of Net Cellular Uptake of Adenosine from the Lumen Side of the Guinea Pig Jejunal Epithelium....Pages 122-130
Uptake of Hypoxanthine in Human Erythrocytes....Pages 131-138
Incorporation of Purine Bases by Intact Red Blood Cells....Pages 139-150
Uric Acid Transport Characteristics in Human Erythrocytes....Pages 151-158
A Relationship between Free Urate, Protein-Bound Urate, Hyperuricemia and Gout in Caucasians and Maoris....Pages 159-162
Influence of Allopurinol on the Genetic Materials of Ehrlich Ascites Tumor Cells....Pages 163-169
6-Azauridine, an Inhibitor of the Purine Salvage Pathway....Pages 170-175
Suppression of Experimental Urate Nephropathy by Salicylate....Pages 176-178
Physiological Characteristics of Various Experimental Models for the Study of Disorders in Purine Metabolism....Pages 179-188
In Vitro Investigations on the Influence of Antirheumatic Drugs on Purine Phosphoribosyltransferases and Their Possible Clinical Consequence....Pages 189-194
Influence of Urate on Connective Tissue Metabolism....Pages 195-200
Protein Binding to Monosodium Urate Crystals and its Effect on Platelet Degranulation....Pages 201-208
Protein Adsorption to Monosodium Urate Crystals: Differential Responses of Human Peripheral Blood Neutrophils....Pages 209-213
Serum Uric Acid Levels in England and Scotland....Pages 214-222
Gout Disease. Its Natural History Based on 1,000 Observations....Pages 223-230
Hyperuricemia as a Risk Factor in Coronary Heart Disease....Pages 231-237
Hyperuricemia and other Cardiovascular Risk Factors....Pages 238-244
Recurrent Gouty Phlebitis without Articular Gout....Pages 245-248
Alterations of Human Purine Metabolism in Megaloblastic Anemia....Pages 249-255
Typing of Uric Acid Level in Cerebrospinal Fluid in Neurological and Psychiatric Diseases....Pages 256-258
Renal Tubular Transport of Urate in Fanconi Syndrome....Pages 259-265
Nutritional State and Purine Metabolism....Pages 266-268
The Effect of Different Purines and Pyrimidines on Human Pyrimidine Biosynthesis....Pages 269-273
The Effect of Weight Loss on Plasma and Urinary Uric Acid and Lipid Levels....Pages 274-277
Pathogenesis of “Fasting Hyperuricemia” and its Prophylaxis....Pages 278-287
The Treatment of Acute Gouty Arthritis....Pages 288-289
Multi-Centre Trial of Naproxen and Phenylbutazone in Acute Gout....Pages 290-296
The Influence of Allopurinol in Customary and in Slow Release Preparation on Different Parameters of Purine and Pyrimidine Metabolism....Pages 297-303
Purine Excretion in Complete Adenine Phosphoribosyltransferase Deficiency: Effect of Diet and Allopurinol Therapy....Pages 304-311
Thiopurinol: Dose-Related Effect on Urinary Oxypurine Excretion....Pages 312-319
Dose-Response Relationship of a Uricosuric Diuretic....Pages 320-327
The Pharmacology of the Hypouricemic Effect of Benzbromarone....Pages 328-333
The Metabolic Effects of Tienilic Acid, a New Diuretic with Uricosuric Properties in Man and Dog....Pages 334-341
Panel Discussion: Hyperuricemia as a Risk Factor....Pages 342-364
Back Matter....Pages 365-373
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