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The effect of route of nutrient administration on the nutritional state, catabolic hormone secretion, and gut mucosal integrity after burn injury.

So that the efficacy of route of nutrient administration in thermal injury could be determined, a comparison was made between immediate enteral vs parenteral feedings in burned guinea pigs. Thirty-five guinea pigs underwent both catheter gastrostomy and jugular vein catheterization. On postoperative day 8, burned animals [30% total body surface area (TBSA)] were divided into an intragastrically (ig) fed group (N = 14) and a parenterally (iv) fed group (N = 14). Animals in each group received 175 kcal/kg/day with a solution of identical nutrient value beginning 2 hr after burn. The body weight change until postburn day (PBD) 8 and the average nitrogen balance were significantly better in the ig group than in the iv group. Values were also higher for the iv group than for the ig group in the early postburn period for urinary vanillyl mandelic acid (VMA) (p less than 0.05), plasma cortisol (p less than 0.05), and plasma glucagon (p less than 0.05). Also, the iv group showed reduced mucosal weight and thickness compared to the ig group on PBD 1 (p less than 0.02). There were significant negative correlations between VMA excretion and body weight change, and between plasma cortisol and jejunal mucosal structure (thickness and weight). These findings suggest that immediate postburn enteral nutrition can provide better nutritional support than parenteral nutrition through the maintenance of gut mucosal integrity and the prevention of increased secretion of catabolic hormones.

Animals↗

Angiography in pheochromocytoma of the urinary bladder. Report of a case.

A case of pheochromocytoma of the urinary bladder in a 20-year-old female is reported. This is the 36th reported case in the English language literature. The patient had classical symptoms of vesical pheochromocytoma with sudden onset of headache, palpitations, and blood pressure elevation during voiding. The provisional diagnosis was arrived at on clinical history, laboratory investigations, including the estimation of catecholamines and vanil mandelic acid (VMA). The diagnosis was confirmed and the tumor was exactly localized by means of angiography. The angiographic appearance of pheochromocytoma of the urinary bladder is not pathognomonic and is similar to that previously described for adrenal pheochromocytoma. Angiography is, with adequate precautions, a safe and useful procedure for ruling out synchronous adrenal or extra-adrenal tumors and for exact localization of the bladder tumor.

Adult↗

Anti-tumor promoting effect of glycosides from Prunus persica seeds.

Four minor components, along with the major cyanogenic glycosides, amygdalin and prunasin, were isolated from Prunus persica seeds (Persicae Semen; Tounin), and characterized as mandelic acid glycosides (beta-gentiobioside and beta-D-glucoside) and benzyl alcohol glycosides (beta-gentiobioside and beta-D-glucoside). The anti-tumor promoting activity of these compounds was examined in both in vitro and in vivo assays. All of the compounds significantly inhibited the Epstein-Barr virus early antigen activation induced by tumor promoter. In addition, they produced a delay of two-stage carcinogenesis on mouse skin that was comparable in potency to (-)-epigallocatechin gallate from green tea. Structure-activity relationships indicated that a substituent at the benzylic position with glycosidic linkage affected the in vitro and in vivo activities with an order of enhancing potency, CN<COOH<H.

Animals↗

Studies on metabolism and toxicity of styrene. V. The metabolism of styrene, racemic, (R)-(+)-, and (S)-(--)-phenyloxiranes in the rat.

Metabolism of styrene, racemic phenyloxirane, (R)-(+)-, and (S)-(--)-phenyloxiranes in rats has been described. The animals excreted phenylethanediol, mandelic acid, phenylglyoxylic acid, and two regioisomeric mercapturic acids in their urine after the intraperitoneal injection of the phenyloxiranes as well as styrene. The mercapturic acids were identified as N-acetyl-S-(1-phenyl-2-hydroxyethyl)cysteine (MA-1) and N-acetyl-S-(2-phenyl-2-hydroxyethyl)cysteine (MA-2). The ratios of the mercapturic acids to the other metabolites excreted in the urine were 1 to 1.8 and 1 to 1.5 for styrene and racemic phenyloxirane, respectively. A remarkable stereoselectivity was observed in the excretion of both types of the metabolites when optically active phenyloxiranes were administered. The rate of excretion of the mercapturic acids was 2.5 times higher than that of the other metabolites when the (R)-oxirane was injected, but the reverse was the case in the (S)-oxirane. The mercapturic acid, MA-1, was excreted at higher rate than the isomer, MA-2, on the administration of styrene and the phenyloxiranes. The most significant regioselectivity in the excretion of MA's was observed when styrene and (S)-phenyloxirane were administered.

Acetylcysteine↗

Asymmetric synthesis and determination of the absolute configuration of FK584, an agent for the treatment of overactive detrusor.

FK584[(-)-N-tert-butyl-4,4-diphenyl-2-cyclopentenylamine hydrochloride, (-)-4-HCl], a potential candidate for the treatment of overactive detrusor, was synthesized in a 4-step approach starting with Sharpless oxidation of cyclopentenol 6 (kinetic resolution). This epoxidation is a rare case in that the empirical rule does not work. Regio- and stereoselective introduction of tert-butylamine to the obtained epoxycyclopentanol 5 and subsequent conversion of the resulting diol to an olefin completed the synthesis. The absolute configuration of FK584 was determined to be S by X-ray crystallographic analysis of the salt of S-(+)-mandelic acid.

Amines↗

Cytogenetic markers, DNA single-strand breaks, urinary metabolites, and DNA repair rates in styrene-exposed lamination workers.

The effect of occupational exposure to styrene on frequencies of chromosomal aberrations and binucleated cells with micronuclei and on single-strand break levels in peripheral blood lymphocytes was studied in 86 reinforced plastic workers and 42 control individuals (including 16 maintenance workers with intermittent, low-dose exposure). In these individuals, the irradiation-specific DNA repair rates and the repair rates of 8-oxoguanines were investigated. We assessed the exposure by measuring the concentrations of styrene in air and in blood and of mandelic acid, phenylglyoxylic acid, 4-vinyl phenol conjugates and regioisomeric phenyl hydroxyethyl mercapturic acids in urine. All these parameters correlated with one another. No clear relationship was found between the styrene exposure and the frequencies of chromosomal aberrations. Binucleated cells with micronuclei were moderately related to the parameters of styrene exposure. We found a negative correlation between all exposure parameters and single-strand breaks. The positive correlation between exposure parameters and DNA repair rates suggests that particular DNA repair pathways may be induced by styrene exposure.

Adult↗

Childhood sporadic pheochromocytoma: clinical profile and outcome in 19 patients.

Sporadic pheochromocytoma is a rare tumor of childhood and accounts for less than 1% of cases of hypertension. We describe the presentation and outcome of 19 adolescents with sporadic pheochromocytoma seen over past 10 years at a tertiary care center in north India. The mean age (+/- SD) at presentation was 15.1 +/- 2.4 years with range from 9-18 years. The male to female ratio was 12:7. The lag time between onset of symptoms to diagnosis ranged from 1 month to 5 years with mean (+/- SD) of 1.09 +/- 1.02 years. The majority of children presented with hypertension and paroxysms. Paroxysms, characterized by the triad of headache, palpitations and sweating, was present in 13 (68%) of these patients. Twelve (63%) patients had postural fall in blood pressure, ten (53%) had abdominal pain, four (21%) had visual blurring, and three (16%) each had palpable abdominal mass and significant weight loss at presentation. Nausea and vomiting are common symptoms in children with pheochromocytoma and were present in six (32%) and three (16%) patients, respectively. Café-au-lait macule was present in only two (11%) patients. Urinary vanilyl mandelic acid (VMA) was found to be significantly high in ten (53%) patients, and urinary epinephrine and norepinephrine in eight (42%). Six (32%) patients had both VMA and urinary epinephrine and norepinephrine within normal limits and five (26%) had significant elevation of both. The tumor was localized by ultrasonography in 17 (89%) patients and by computed tomography in 18 (95%), and in one patient it was localized by 131I-MIBG scan. Sixteen (84%) patients had adrenal pheochromocytoma (including four with bilateral masses), while the remaining three (16%) had abdominal extra-adrenal pheochromocytoma originating from sympathetic ganglions. The mean (+/- SD) diameter of the tumor was 4.4 +/- 1.7 cm, ranging from 2.2-7.5 cm. Pre-operatively, hypertension was managed by phenoxybenzamine in six (32%), sustained release prazosin in 12 (63%), beta-blockers in 14 (74%), calcium channel blockers in 12 (63%), and angiotensin converting enzyme inhibitors and diuretics in only two (11%) patients. Eighteen (85%) patients underwent exploratory laparotomy for removal of the tumor. On follow-up, 13 (72%) patients became normotensive, while six (32%) patients continued to have hypertension. In conclusion, childhood pheochromocytoma is characterized by atypical symptomatology; ultrasonography is a useful modality in localizing the lesions in the majority of patients; surgery is rewarding in most patients.

3-Iodobenzylguanidine↗

Urinary metabolites of tryptophan, serotonin and norepinephrine in alcoholics.

Levels of tryptamine, 3-methoxy-4-hydroxy phenylethylene glycol, 3-methoxy-4-hydroxy mandelic acid and the tryptamine: 5-hydroxyindole-3-acetic acid ratio differed between alcoholics, healthy volunteers and patients with nonalcoholic liver disease. There was no correlation between amine metabolite levels and results of liver function tests.

Adult↗

Serum neuron-specific enolase as a marker useful for monitoring the effectiveness of therapy in patients with neuroblastoma--as compared with urinary catecholamine metabolites.

Neuron-specific enolase (NSE) in sera of 3 patients with neuroblastoma (Stage IV) were measured by radioimmunoassay, as compared with urinary catecholamine metabolites (vanillyl-mandelic acid (VMA) and homovanillic acid (HVA] during the course of chemotherapy, radiation, and second look operation. In Case 1 (Stage IV B) and Case 3 (Stage IV A), NSE-level on admission was found to be elevated to 51.0 ng/ml and 25.5 ng/ml, respectively. VMA and HVA were also elevated. In Case 2 (Stage IV A), NSE on admission was elevated to 128.0 ng/ml., HVA was high, but VMA was within normal range. From 1 to 3 weeks after chemotherapy and radiation, high levels of urinary VMA and/or HVA in patients promptly decreased within normal range. The size of primary tumor masses either showed no marked change or slightly decreased by radiological examinations. After intensive chemotherapy, high levels of serum NSE decreased within normal range. At that time, second look operations were carried out. The size of primary tumors was reduced (3.6 X 2.7 X 2.1 cm in average) and almost all masses had scarred over. These data suggest that serum NSE levels correlate very well with residual tumor burdens.

Catecholamines↗

Human pheochromocytoma: different patterns of catecholamines and chromogranins in the intact tumour, urine and serum in clinically unsuspected cases.

Clinically unsuspected pheochromocytoma is usually discovered either at autopsy or during surgical intervention for unrelated conditions, despite often enormous neoplastic masses producing and storing catecholamine (CA). In order to assess whether these tumours share some common features we have compiled data for six patients admitted to hospital without previous diagnosis of their pheochromocytoma. The clinical variables and the morphological and immunohistochemical characteristics of the tumours revealed that these cases represented quite different expressions of adrenomedullary neoplasms. They differed not only with respect to nuclear ploidity and overall cytoplasmic morphology but also in catecholamine storage and expression of immunoreactive chromogranin A sequences in the intact tissue. In two of the patients hypertension had been overlooked as a diagnostic indicator of their CA-producing tumours. There was no clear relationship between the mean arterial pressure, the tumour content of CA and the serum levels of CA. Processed chromogranin A dominated in the serum of the two hypertensive cases. The 24-h urine values of CA and its main metabolite (vanillin mandelic acid) were, together with the serum values of chromogranin A and B, proportional to tumour mass and provided the most reliable diagnostic indicators for the non-hypertensive as well as the hypertensive cases.

Adrenal Gland Neoplasms↗

The metabolism of ethylbenzene hydroperoxide in the rat.

Ethyl[14C]benzene hydroperoxide administered orally to female rats (30 mg/kg) is rapidly absorbed and metabolized. Most of the administered compound (81%) is eliminated in the 0-24 h urine. Major metabolites include mandelic acid (23%), hippuric acid (34%) and 1-phenylethyl glucuronide (4%). Ethyl[14C]benzene is metabolized via 1-phenylethanol to the same mixture of metabolites as obtained with the hydroperoxide. Biotransformations of the hydroperoxide and their likely biochemical mechanisms are discussed.

Animals↗

Urinary catecholamines and their metabolites in management of neuroblastoma.

Measurements of urinary total catecholamines expressed as dopamine (TC) and their metabolites, total metadrenalines (TM) and 3-methoxy-4-hydroxy mandelic acid (HMMA) were made on 24-h urine collections from 56 previously untreated children with neuroblastoma. All results were expressed as a ratio to the creatinine excretion and were compared with "smoothed" age-related reference ranges derived from results in 704 children with other illnesses. Urinary catecholamines/metabolites excretion was elevated in 55 of the 56 patients, the exception being a baby with opsomyoclonus. TC was raised in 47, HMMA in 41, and TM in 37. Eleven patients had elevations of one parameter (TC in 10, HMMA in 1), 15 had 2 elevated levels, and 29 had elevations of all three. The TM level was the least contributory, as in no patient was it the only parameter elevated. Serial measurements were performed in 40 children, and the results correlated closely with the clinical progress of the disease and in some children permitted early detection of recurrence.

Catecholamines↗

Role of sympathetic nervous system in experimental hypertension and diabetes mellitus.

An investigation has been made to elucidate the role of sympathetic nervous system (SNS) in the development of renal hypertension and hyperglycemia in rats and rhesus monkeys using 6-hydroxydopamine (6-OHDA). Development of renal hypertension was blocked in weanling rats (80%), demedullated adult rats with 6-OHDA (75%) but not in adult rats sympathectomised with 6-OHDA. Weanling rats treated with 6-OHDA did not have any detectable catecholamine stores when measured 60 days after treatment with 6-OHDA. Unlike the weanling rats the hearts of the adult rats showed significant refilling of catecholamines 60 days after 6-OHDA treatment. 6-OHDA treatment and adrenalectomy did not modify the development of streptozotocin (STZ) induced hyperglycemia and the hypoglycemic effect of tolbutamide and phenformin. Chemical sympathectomy with 6-OHDA did not show any glucose intolerance in rhesus monkeys or any effect or insulin release. Phentolamine (PHE) and oxprenolol (OXP) pretreatment had no effect on development and maintenance of hyperglycemia. Although there was no effect on the endogenous catecholamines stored in the heart and brain in the diabetic rats, there was a marked increase in the urinary excretion of norepinephrine (NE), epinephrine (E), 3-methoxy-4 hydroxy mandelic acid (VMA) and creatinine. The rate of disappearance of (3H)-NE from rat heart was higher when compared to age matched controls. Diabetic rats showed increase responsiveness to angiotensin II and developed hypertension faster when their renal arteries were clamped as compared to controls. It is concluded that the functional SNS is important in the development of renal hypertension in the rat. Further the SNS in the rats and rhesus monkeys does not play any significant role in the STZ induced hyperglycemia, glucose intolerance and insulin release.

Adrenalectomy↗

[Determination of VMA/Cr and HVA/Cr in random urine collection for the diagnosis of neuroblastoma]

OBJECTIVE: To evaluate the VMA/Cr and HVA/Cr of random urine in the diagnosis of neuroblastoma. METHODS: VMA/Cr and HVA/Cr were examined in 50 normal children and 11 cases of neuroblastoma (NB) aged 1 approximate, equals 5 years. The concentration of 4-hydroxy-3-methoxy-mandelic acid (VMA) and homovanillic acid (HVA) in random urine collection were analyzed by high-performance liquid chromatography and creatinine (Cr) analyzed by auto-biochemical analyzer. RESULTS: The normal range of VMA/Cr and HVA/Cr were <14.9 mmol/mol and <23.8 mmol/mol, respectively. The positive rate of VMA/Cr and HVA/Cr in NB patients was 90.9%. CONCLUSION: Determination of VMA/Cr and HVA/Cr in random urine collection can be used for NB diagnosis.

Journal Article↗

Neuroendocrine effects of styrene on occupationally exposed workers.

The serum levels of prolactin (PRL), human growth hormone (HGH), thyroid-stimulating hormone (TSH), and the gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were measured in 30 females exposed to about 130 (range 65-300) ppm of styrene in the air and in 30 age-matched referents to show whether styrene exposure influences the dopaminergic tuberoinfundibular system (TIDA). The exposed subjects' serum levels of PRL were more than double the reference values and were significantly related to the urinary excretion of styrene metabolites, ie, to the sum of mandelic acid (MA) and phenylglyoxylic acid (PGA) in the "next-morning" urine spot sample. Such a relationship still proved to be statistically significant after the removal of the effects of age and duration of exposure with the method of partial correlation. The serum concentrations of HGH in the exposed workers were also higher than in the reference group. Though within the reference levels, the TSH values of the exposed subjects were significantly related to the urinary excretion of MA and PGA. These results are consistent with the dose-dependent depletion in tuberoinfundibular dopamine after experimental styrene exposure of rabbits.

Adult↗

[Adrenal tumors found by chance. Surgical treatment or follow-up?].

206 case records of the patients treated from 1985 to 1998 for various diseases of the adrenal glands were analyzed. In 39 (18.9%) patients tumors were chance finding at ultrasound examination or computer tomography of the abdominal cavity and retroabdominal space. 25 patients from this group were operated on, 14 patients were not operated and were followed up from 1 month to 7 years. All the patients underwent complex examination including analysis of the complaints, anamnesis and physical examination data, hormonal status examination (ACTH, hydrocortisone, 11-oxycorticosteroids, 17-ketosteroids, aldosterone, renin, adrenalin, noradrenalin, vanillyl-mandelic acid), device methods of examination USE, CT, MRT, superselective phlebography with separate catheterization of adrenal veins and blood intake per floor, fine needle aspiration biopsy under ultrasound control. Comparison of the results of complex clinical examination with morphological data of removed adrenal glands was carried out retrospectively. Arteriography and superselective phlebography with separate catheterization of adrenal veins and per floor taking of blood samples, performed in 36 patients, enabled not only to supplement and define more exactly the other methods of topical diagnosis, but also to asses objectively functional actively of the affected and contralateral adrenal. Despite the fact that during the study of hormonal level in peripheral blood of patients it was normal analysis of the data obtained by superselective phlebography of adrenal veins and per floor taking of blood samples showed significant increase in hormones level in blood of all operated patients. Comparison of the data of superselective phlebography with separate catheterization of adrenal veins and per floor taking of blood samples and clinical picture of the disease made it possible to suggest the presence of preclinical (subclinical) Cushing or Conn syndrome. Operative treatment was not indicated in the absence of hormonal activity of the tumor (i.e. preclinical syndromes by Icenko-Cushing, Conn, pheochromocytoma, the virilizing and feminizing tumors), tumors of small size (less than 3 cm), in absence of malignant growth features confirmed by complex instrumental examination (USE, CT, MRT, fine-needle aspiration biopsy under US control, superselective phlebography with per floor taking of blood samples). Such patients were reexamined in 6 months. During the follow up period no changes of tumor size, homogeneity, hormonal status were revealed.

Adrenal Cortex Hormones↗

[Noninvasive screening for pheochromocytoma in patients with an incidentally discovered adrenal mass: usefulness of provocative test with metoclopramide and 131I-metaiodobenzylguanidine scintigraphy].

Pheochromocytoma accounts for approximately 25% of incidentally discovered adrenal masses. Certain diagnostic procedures (e.g., adrenal arteriography, needle biopsy of an adrenal mass), anesthesia and abdominal surgery may cause a sudden release of catecholamines from a pheochromocytoma and induce paroxysmal attacks of hypertension. In addition, pheochromocytoma is well known to cause unsuspected operating room deaths. Therefore, we must carefully separate this functioning neoplasm from other types of adrenal masses. In this study, we compared the results of noninvasive tests including (1) assay of urinary catecholamines and their metabolites, (2) a provocative pharmacologic test using metoclopramide (MCP test), and (3) 131I-metaiodobenzylguanidine (MIBG) scintigraphy to screen for pheochromocytoma in 10 consecutive patients with an incidentally discovered adrenal mass (6 pheochromocytomas and 4 non-functioning adrenocortical adenomas). We measured the 24-hour urinary excretion of catecholamines, metanephrines and vanillyl mandelic acid in all 10 patients; 5 were positive, 4 were negative and 1 was false-negative (sensitivity = 83%, specificity = 100%). The MCP test was performed in 7 patients; 3 were positive, 3 were negative and 1 was false-negative (sensitivity = 75%, specificity = 100%). MIBG scintigraphy was performed in 7 patients; 4 were positive, 1 was negative and 2 were false-negative (sensitivity = 67%, specificity = 100%). According to these results, all patients with an incidentally discovered adrenal mass should undergo a determination of the 24-hour urinary excretion of catecholamines and their metabolites, including metanephrines. If this urine assay is negative, other noninvasive tests including the MCP test and MIBG scintigraphy should be considered in selected patients with radiographic characteristics of pheochromocytoma.

3-Iodobenzylguanidine↗