Hippuric Acid Synthesis Research Articles

HAP-TiO2 nanocomposites based electrochemical sensor for selective and simultaneous detection of para-aminohippuric acid and uric acid

Kidney diagnosis by p-aminohippuric acid (PAH) test indicates the ability of the kidney to combine benzoic acid with PAH by determination of the latter eliminated in urine or blood serum. Hippuric acid synthesis also occurs in both the liver and cortical cells of the kidney. However, the PAH test did not become popular because of the non-availability of a simple method for quick and accurate determination of the PAH at an affordable cost. Here, we report a novel electrochemical sensor based on hydroxyapatite-titanium dioxide (HAP-TiO2) nanocomposite for quantifying specific biomarkers PAH and uric acid (UA). Nanostructured HAP and TiO2 powders have been synthesized independently by microwave irradiation and hydrolysis methods respectively and the composites are prepared by mixing the appropriate amounts of HAP and TiO2 under sonication. Voltammetric studies of HAP-TiO2 modified glassy carbon electrodes exhibited improved electrocatalytic activity towards the oxidation of PAH and UA in a phosphate buffer saline (pH7.0). Under the optimized conditions, the oxidation peak currents are linearly proportional to PAH and UA concentrations over wide linear ranges of 50 nM to 5.760 mM, and the corresponding lowest detection limits are estimated to be 37 nM and 43 nM (S/N = 3). The fabricated electrode has been successfully implemented for the determination of PAH and UA in human urine samples. Performance of the device in terms of sensitivity, specificity, and linear range fulfills the requirement for screening the chosen biomarkers simultaneously making it suitable for clinical non-invasive liver and kidney diagnoses.

Evaluation of liver function by co-administration methodology using 13C-labelled benzoic acid and hippuric acid coupled with nuclear magnetic resonance spectroscopy.

The amount of hippuric acid synthesized and excreted in the urine after benzoic acid loading (hippuric acid test) is a useful index of liver function. However, the hippuric acid test gives erroneous results in the event of failure of renal excretory function. A new stable isotope co-administration methodology using nuclear magnetic resonance (NMR) spectroscopy has been developed to overcome this defect. [7-(13)C]Benzoic acid and [glycine carbonyl-13C]hippuric acid ([gly-13C]hippuric acid), each 0.4-0.6 mmol kg(-1) were simultaneously administered intravenously as probes to normal or liver-injured rats and the urine was analysed by 100 MHz 13C NMR spectroscopy. Consequently, urinary excretion of [7-(13)C]hippuric acid formed from [7-(13)C]benzoic acid and [gly-13C]hippuric acid was successfully traced with very simple and convenient procedures. The urinary excretion of [7-(13)C]hippuric acid indicated the combined functions of hippuric acid synthesis and renal excretion, whereas that of [gly-13C]hippuric acid was indicative of renal excretion of hippuric acid only. The heights of resonances for C7 of [7-(13)C]hippuric acid and the glycine carbonyl carbon of [gly-13C]hippuric acid were used to calculate the concentrations of labelled hippuric acids. [7-(13)C]Hippuric acid was excreted more slowly than [gly-13C]hippuric acid by both normal and liver-injured rats. The liver-injured rats excreted the labelled hippuric acids more slowly than the normal rats. The kinetic parameters were computed for the individual rats on the basis of Michaelis-Menten elimination for benzoic acid and first-order elimination for hippuric acid. The maximum rates of metabolism (Vmax) (4.8-5.8 micromol min(-1) kg(-1)) and the renal elimination rate constants of hippuric acid (Kre) (0.010-0.021 min(-1)) in the liver-injured rats were lower than those (Vmax 6.7-11.8 micromol min(-1) kg(-1); Kre 0.026-0.045 min(-1)) in the normal rats. These results have demonstrated that liver function can be evaluated from the Vmax value even though the renal function of hippuric acid excretion (Kre) is impaired. Thus the co-administration methodology is feasible and can remove the defect of the previous hippuric acid test. These results could form the basis for a more convenient and reliable hippuric acid test in man.

Benzoylalanine: detection and identification of an alanine conjugate with benzole acid in hyperammonemic patients treated with sodium benzoate

Urine of four hyperammonemic patients who were treated with large amounts of sodium benzoate were analyzed. Gas chromatographic and gas chromatograph-mass spectrometric analysis showed the presence of large amounts of benzoylalanine in addition to much hippuric acid. Benzoylalanine was identified by comparison with an authentic standard by means of its mass spectrum and the gas chromatographic retention time of its trimethylsilyl derivative. This abnormal metabolite is thought to be derived from the conjugation of benzoyl CoA with alanine. It is suggested that the excretion of benzoylalanine results from a reduction in the liver free glycine level caused by hippuric acid synthesis.

The absence of hippuric acid synthesis in the Indian fruit bat

Indian fruit bats ( Pteropus giganteus ) do not convert injected [ 14C] benzoic acid into hippuric acid. Homogenates of fruit bat liver or kidney were unable to convert benzoic acid into hippuric acid. The main urinary metabolite (80–90% of dose) of benzoic acid in the fruit bat was benzoylglucuronide. Hippuric acid was not detectable in normal Indian fruit bat urine.

Liver Function Tests in Rheumatoid Arthritis

(1972). Liver Function Tests in Rheumatoid Arthritis. Scandinavian Journal of Rheumatology: Vol. 1, No. 1, pp. 184-195.

Hepatic dysfunction in human trypanosomiasis: I. Abnormalities of excretory function, seroflocculation phenomena and other tests of hepatic function with observations on the alterations of these tests during treatment and convalescence

1. 1) Though clinical jaundice is uncommon in T. rhodesiense infections in man, an increase in the total serum bilirubin is common in early cases in the acute febrile stage. A raised serum bilirubin level was common even in very early cases with a trypanosome chancre. The serum bilirubin was not raised in six consecutive chronic late cases. 2. 2) Excess urobilinogen in the urine was found in 83 per cent. of early cases, 67 per cent. of the intermediate and only 40 per cent. of the late cases. Bilirubinuria occurred in 80 per cent. of the early cases but was less common and less severe in the late. 3. 3) The bromsulphthalein tolerance test was always abnormal in the acute febrile early case, but was normal in clinically mild apyrexial cases. The test became normal rapidly after treatment. Those late cases of T. rhodesiense and T. gambiense infections which were examined, showed abnormalities of BSP tolerance, which also became normal rapidly after treatment. 4. 4) The BSP tolerance test became normal before the serum bilirubin had returned to normal. 5. 5) The seroflocculation abnormalities in 46 early cases and in 10 late cases of T. rhodesiense infections are described. Similar abnormalities were noted in two late cases due to T. gambiense. The improvements of these tests during recovery are described. 6. 6) Abnormal hippuric acid synthesis was noted in one late case due to T. gambiense, and in another due to T. rhodesiense. This test became normal soon after treatment was begun. 7. 7) The clinical and biochemical investigations indicated that, in T. rhodesiense infections in man, there is a parenchymatous disorder of the liver of greatly varying severity which is reversible by specific treatment with suramin or mel B. Hepatic dysfunction may be responsible for the intolerance of severely ill cases to mel B. Because of this, Apted's (1953, 1957) cautious approach to treatment is to be commended.

Hepatic dysfunction in human trypanosomiasis: II. Serum proteins in Trypanosoma rhodesiense infections and observations on the alterations found after treatment and during convalescence

1. 1) The results of the analysis of serum proteins by electrophoresis are described in 26 early cases and 10 late cases of T. rhodesiense infection in man. 2. 2) In early cases in the acute febrile stage there is a reduction in total protein and serum albumin. This reduction precedes any rise in γ-globulin and is corrected during treatment and subsequently. 3. 3) Individual early cases may show an increase in serum γ-globulin on admission, which declines on treatment and subsequently. 4. 4) Some early cases show a rise in γ-globulin after treatment, which declines subsequently. 5. 5) Other disorders of hepatic function are described in a very early case with a trypanosome chancre. The associated serum protein alterations are also described. The abnormalities of the hippuric acid synthesis test, the bromsulphthalein tolerance test and serum bilirubin are described; these tests became normal before the serum proteins. 6. 6) In late cases the serum albumin is low and the serum γ-globulin is high. Very high γ-globulin levels are found characteristically in the chronic “tolerant” late case. The “intolerant” very wasted case showed marked reduction in serum albumin and very low total protein. 7. 7) Seroflocculation tests improve concurrently with serum proteins and reflect the “balance” of these proteins but a quantitative relationship could not be determined. 8. 8) The pathogenesis of serum protein changes is discussed.

Studies on the determination of the human glycine pool

1. 1. Studies on the human glycine pool were carried out by means of hippuric acid synthesis using 15N-labeled glycine. The size of the human glycine pool was calculated from the content of 15N in urinary hippuric acid. 2. 2. The normal range was found to be 34.3 to 48.1 mg N/kg body weight; these values were discussed. 3. 3. The size of the glycine pool of patients with various liver diseases was compared with the normal values. In acute liver diseases, the size of the glycine pool was generally larger. On the other hand the size of the glycine pool was found to be smaller in chronic cases.

Studies on the metabolism of pantothenic acid in liver damage. II. Pantothenic acid treatment in patients with liver disease.

Twenty mg of calcium pantothenate was administered intramuscularly daily for 1-4 weeks to patients with various liver diseases. Improvement in hippuric acid synthesis, serum cholesterol ester ratio, acetylating activity and α-keto acid metabolism was observed. However, other tests of liver function were not improved or only slightly it at all. Favorable effects upon fatiguability, anorexia and nervous complaints including paresthesias were also observed.

Studies on the metabolism of pantothenic acid in liver damages. I. Urinary excretion of pantothenic acid in patients with various liver diseases and its correlation with liver function.

1. Urinary excretion of PaA and the increase in the excretion of the vitamin following pantothenate administration were measured in 52 patients with various liver damages. Mutual relations with various liver functions were also studied.2. Both urinary PaA and the increase in excretion following intramuscular administration of the vitamin were reduced in most patients in comparison with those in normal adults.In relatively severe cases, increase in PaA excretion following intramuscular administration of the vitamin was frequently found to be greater than that of normal persons.3. Correlation was found between PaA excretion and various liver functions, especially, TTT, serum cholesterol ester ratio, hippuric acid synthesis and blood pyruvate level.4. The results mentioned above led to the conclusion that a metabolic disturbance of PaA may exist in liver damages leading to the impairment of liver functions, especially, hippuric acid synthesis, and the metabolism of α-keto acid and cholesterol.

Liver Function Tests in Rheumatoid Arthritis

SummaryTo illustrate the possible appearance of liver function disturbances in connection with rheumatoid arthritis, we have made nine different liver function tests simultaneously on 116 patients suffering from this disease.From the results it appears that in protein metabolism tests more than 55.4 per cent of the cases gave abnormal albumin/globulin ratios and Takata and CdSO4 readings. This was more common in severe cases of the disease.In 41 per cent of the cases the galactose tolerance test gave pathological readings.The total serum cholesterol appeared to be on the same level as in normal material.The bilirubin concentration appeared to be normal. In more severe cases of the disease these values seemed to be lower than in milder forms.The detoxication capacity determined by Quick's hippuric acid synthesis test had decreased in a quarter of the cases examined. Values below normal appeared more frequently in severe cases of the disease.The dye excreting capacity, determined by the bromsulfalein tolerance test, was found to be reduced in 17 per cent of the cases examined. These results were independent of the severity of the disease.

Conversions of (3‐pyridyl)‐methanal

AbstractThe reactions are described of (3‐pyridyl)‐methanal with acetic anhydride (formation of (3‐pyridyl)‐acrylic acid), with hippuric acid (synthesis of β‐(3‐pyridyl)‐alanine), with phenyl‐magnesium bromide (synthesis of (3‐pyridyl)‐phenyl‐carbinol), with the iodomethylate of α‐picoline, and with dimedone. (3‐pyridyl)‐methanal does give the Cannizzaro reaction, but not the pyridoin condensation.

Hippuric acid synthesis in man after the administration of [alpha-14C]Glycine.

Hippuric acid synthesis in man after the administration of [alpha-14C]Glycine.

Hippuric acid synthesis in the rat

Hippuric acid synthesis in the rat

The Validity of Laboratory Evidence in the Diagnosis of the Sequelae of Acute Hepatitis

Summary Twenty-one patients, who had had acute hepatitis from six months to ten years before were studied by means of a group of laboratory procedures which included serum bilirubin determinations, examination of the urine for urobilinogen, the bromsulf alein test, hippuric acid synthesis, determination of the serum cholesterol, and of the prothrombin level, the cephalin cholesterol flocculationtest, thymol turbidity and thymol flocculation tests, and colloidal gold reaction. Five of these patients had symptoms suggesting chronic active hepatitis, seven had hepatomegaly. The others had no clinical evidence of hepatic disease. Some abnormality in the responses to one or more of these tests was noted in all of the patients. In two patients who were symptom-free, however, the only abnormality was very slight hypercholesterolemia, which may be considered to be of only questionable significance. The hippuric acid synthesis test was not abnormal in any of the eighteen patients in whom it was performed. The amount of urobilinogen in the urine was normal in twenty of the twenty-one patients studied. These two tests seemed relatively insensitive in detecting residual hepatic changes following hepatitis. The various flocculation tests gave normal responses in all but four of the patients. The cephalin cholesterol flocculation was positive in two and the colloidal gold reaction was positive in three. In only two patients were the flocculation tests strikingly abnormal. Although one of these two patients had clinical evidence of active liver disease, such evidence was much less pronounced in the other patient, so that in these two individuals no correlation between positive flocculations and the clinical features of hepatitis could be observed. In general the flocculation tests were of little value in the recognition of residual liver dysfunction. Hyperbilirubinemia was found in fourteen of the twenty-one patients. This consisted of increase in only the direct reacting bilirubin in nine of the fourteen patients. No instance of marked increase in the indirect reacting bilirubin was seen. The degree of hyperbilirubinemia was slight in most instances, but even this slight increase in bilirubin may have diagnostic significance and indicate definite hepatic dysfunction since it was not encountered without other evidence of liver disturbance. Some degree of excessive bromsulf alein retention was also encountered in fourteen of the twenty-one patients studied. This was also usually of slight degree. Although found frequently, bromsulf alein retention was occasionally absent in the face of other evidence of hepatic dysfunction, so that a normal response to the bromsulf alein test may not be considered as excluding the presence of residual hepatic dysfunction following hepatitis. In eight of the twenty-one patients, a low prothrombin level was found. All eight of these patients had abnormal responses to one or more of the other tests used, but in some instances the hypoprothrombinemia was the most striking laboratory evidence of hepatic disorder. Vitamin K was given to five of these eight patients and the prothrombin level responded slowly or not at all to this therapy. The hypothrombinemia seems, therefore, to indicate that a specific liver dysfunction remained following acute hepatitis. Determination of prothrombin is suggested as a valuable addition to the liver function tests usually employed in the search for sequelae of hepatitis. The abnormality may exist even though other liver function tests are relatively normal. Lowering of the cholesterol ester ratio, was seen in only one patient and only one patient had decrease of the total cholesterol. Ten of the twenty-one patients had hypercholesterolemia. Although this finding need not indicate dysfunction of the liver, its demonstration in association with other laboratory evidence of hepatic disturbance following hepatitis calls for further investigation. In this group of patients we could not find any close relation between the clinical features—symptoms and hepatomegaly—and the responses to the liver function tests used. Patients who had had acute hepatitis not infrequently gave abnormal responses to various liver function tests. The degree of abnormality was often slight and not necessarily indicative of disease that was active clinically. The prognostic significance of such findings can be determined only by repeated studies.

HIPPURIC-ACID SYNTHESIS TEST OF - LIVER FUNCTION: SOME DIFFICULTIES IN INTERPRETATION

HIPPURIC-ACID SYNTHESIS TEST OF - LIVER FUNCTION: SOME DIFFICULTIES IN INTERPRETATION

Cirrhosis of the liver

Abstract 1.1. A study of the effects of the intravenous administration of amino acids to five patients with cirrhosis of the liver is presented. 2.2. Clinically, one patient exhibited great general improvement; three exhibited moderate general improvement, and one remained unchanged. 3.3. The most striking result was shrinkage in the size of the liver and spleen, possibly attributable to resorption of intracellular fat in the liver, with circulatory readjustments secondary to the improved portal circulation resulting in decrease in splenic congestion. 4.4. Peripheral edema subsided in all patients exhibiting it within two weeks after the initiation of amino acid therapy. 5.5. Laboratory data accumulated during a preliminary period of observation and at the conclusion of a period of amino acid administration indicated an improvement in glucose tolerance and in hippuric acid synthesis in all patients, and an improvement in bromsulfalein excretion in one patient. 6.6. Further study and corroboration is needed to determine the degree of benefit obtainable by the use of amino acids in cirrhosis of the liver.

The Clinical Application of the Hippuric Acid and the Prothrombin Tests

A survey of recent advances in medicine and surgery yields numerable examples of problems solved by laboratory methods which had completely defied all approaches by purely clinical means. No better illustration can be cited than the recognized dangers confronting the jaundiced patient who required surgical treatment. All the surgeon's clinical experience availed him little in determining the extent to which the liver had been injured; nevertheless this information was highly desirable for determining the type of anesthesia, the possible postoperative course, and numerous other factors. Furthermore while it was clearly recognized that every jaundiced patient was potentially in jeopardy of serious and occasional fatal hemorrhage, it was neither possible to predict clinically which subjects would bleed, nor to take steps to prevent this catastrophic complication. Two simple tests developed during the past six years have been accepted rather widely by American surgeons as definite aids, particularly in the surgery of the biliary tract in meeting the two problems just presented. The first of these tests is the hippuric acid synthesis as a means for determining liver function; the second, the quantitative method for estimating the prothrombin concentration of the blood.

DETOXICATION OF SODIUM BENZOATE IN NEUROPSYCHIATRIC DISORDERS

The rate of detoxication of benzoic acid was determined in patients with various neuropsychiatric diseases. About one half of the patients with catatonia showed a defect in hippuric acid synthesis. This may be due to the state of muscular rigidity and immobility of these patients. Deteriorated patients with epilepsy showed a defect in the synthesis of hippuric acid, whereas extramural patients with epilepsy showed a normal excretion of the equivalent benzoic acid. This may indicate a defect in glycine synthesis in deteriorated patients with epilepsy. Normal average values were found in post-encephalitic Parkinsonism and multiple sclerosis. A patient with progressive muscular dystrophy was able to synthesize glycine at a normal rate.

The Role of the Liver in Hippuric Acid Synthesis

The Role of the Liver in Hippuric Acid Synthesis