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Chemical control of hyperfibrinolytic states by synthetic inhibitors of fibrinolytic enzymes.

The effects of two types of synthetic inhibitor of fibrinolytic enzymes (omega-aminocarboxylic acids, benzamidine derivatives) on intravascular fibrinolysis and fibrinogenolysis were studied in rats. Generalised primary fibrinogenolysis was produced by infusion of human plasminogen-streptokinase complex, secondary fibrinolysis was induced by infusion of the thrombin-like enzyme batroxobin. The inhibitors exerted different effects on the hyperfibrinolytic states. The omega-aminocarboxylic acids (PAMBA, AMCA) inhibited fibrinolysis more effective than fibrinogenolysis. In contrast, the benzamidines (APPA, NANP) were more potent inhibitors of fibrinogenolysis. Aprotinin examined for comparison behaved like the benzamidine derivatives.

4-Aminobenzoic Acid↗

Pancreolauryl test for pancreatic exocrine insufficiency.

Pancreolauryl test (PLT), a tubeless pancreatic function test, was performed in 40 consecutive patients suffering from chronic pancreatitis, in 21 patients with miscellaneous digestive diseases, and in 18 control subjects to assess its diagnostic sensitivity and specificity. N-benzoyl-L-tyrosyl-p-aminobenzoic acid test (PABA test) and secretin-cerulein test were also carried out to compare the diagnostic value of PLT with that of these two pancreatic function tests. PLT was abnormal in 22 of 40 patients with chronic pancreatitis (55%). In particular, pathological results were found in all patients with severe pancreatic insufficiency and only in four of 14 patients with mild to moderate insufficiency. PABA test showed a slightly lower sensitivity in severe insufficiency, and the same sensitivity in mild-moderate insufficiency. PLT was normal in all control subjects and in 17 of 21 patients with nonpancreatic digestive diseases. Its specificity (90%) was slightly higher than that of PABA test (82%). The results indicate that PLT may be used to support a diagnosis of severe pancreatic exocrine insufficiency, while in mild or moderate insufficiency its diagnostic value is limited.

4-Aminobenzoic Acid↗

Clinical and laboratory characterization of Basenjis with immunoproliferative small intestinal disease.

Eleven adult Basenji dogs with immunoproliferative small intestinal disease (IPSID) were studied. Two items of history related to the digestive tract were characteristic: (i) chronic intractable diarrhea in most dogs, and (ii) progressive emaciation. Anorexia was intermittent in only a few dogs. In addition, skin lesions of various degrees of severity were observed, including alopecia of pinnae and ventrum, hyperpigmentation and hyperkeratosis of pinnae, and necrosis and ulcerations of margins of pinnae. The cause of the skin lesions was not determined; however, hypothyroidism did not appear to contribute to the skin changes. Standard hematologic and serum chemical values were not consistently abnormal. However, a poorly regenerative anemia, mild neutrophilia, and increased aspartate aminotransferase and alanine aminotransferase activities were generally observed in severely affected dogs. The Pelger-Huet anomaly was identified in dog 3. Maldigestion and malabsorption as determined by the N-benzoyl-L-tyrosyl-p-aminobenzoic acid and d-xylose test was documented to varying degrees in dogs with IPSID. Maldigestion was correlated with functional pancreatic exocrine insufficiency. Severe malabsorption was documented in only 3 dogs. Serum gastrin values were evaluated in these dogs because of a prior observation of parietal cell hyperplasia and gastric ulceration. Hypergastrinemia was documented in 3 dogs. Additional studies will be necessary to determine whether an acid hypersecretory state contributes to the pathogenesis of IPSID in Basenjis.

4-Aminobenzoic Acid↗

Infantile methemoglobinemia induced by a topical anesthetic, Cetacaine.

A 2-month-old infant developed severe methemoglobinemia following topical pharyngeal application of a common benzocaine containing agent ( Cetacaine ). Although a number of reports of this complication have appeared in recent years, this is apparently the first case reported in the Otolaryngology literature. The pathophysiology, pharmacology, and treatment of this condition are reviewed.

4-Aminobenzoic Acid↗

Effect of [3H]methotrexate impurities on apparent transport of methotrexate by a sensitive and resistant L1210 cell line.

Transport of methotrexate by L1210 sensitive and resistant cell lines was studied using [3H]methotrexate and methotrexate. The intracellular and cellular efflux of drug was analyzed by radioligand binding assay and high performance liquid chromatography. It was shown that the initial, rapid uptake of [3H]methotrexate was not methotrexate but rather [3H]p-aminobenzoylglutamate, even when the [3H]methotrexate was greater than 97% homogeneous. In the mutant cell line, the impurity could account for all of the apparent methotrexate uptake at 1 to 10 micro M extracellular drug. Similarly, the rapid efflux of [3H]methotrexate was also shown to be all, or in part, 3H-impurities, in both the mutant and sensitive cell lines. These results do not conflict with the currently accepted model of a carrier-mediated process for reduced folate and antifolate transport but do suggest that the quantitative interpretation of the early time points of transport experiments be more critically evaluated, especially when mutant cell lines are being analyzed.

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B.T.PABA test: a new absorption test.

B.T.PABA has been evaluated as a new pancreatic exocrine function diagnostant. In this study, it was used as a new absorption test. After ingestion of 1 gm of B.T.PABA and the test meal, PABA in 6-h collected urine was determined. The urinary PABA excretion rate in Billroth I type postgastrectomy patients, 8-14 days after surgery, was lower than that of controls and that in Billroth II patients, 10-14 days after surgery, was the lowest of the three. However, the PABA excretion values of postgastrectomy patients 10 months to 20 years after surgery recovered nearly to the normal level of PABA excretion. These decreases in PABA excretion were considered to be caused by postgastrectomy digestion-absorption impairment. In addition, there was a significantly high correlation between the conventional 131I-labeled albumin absorption test and the B.T.PABA test. Therefore, it was concluded that the B.T.PABA test can be used as a simple absorption test.

4-Aminobenzoic Acid↗

[Antifibrinolytic therapy of subarachnoid hemorrhage. Permeation of oral paraaminomethylbenzoic acid in the cerebrospinal fluid].

Studies of the permeation of PAMBA in the cerebrospinal fluid of patients with intact or disturbed BBB function after oral administration of 6 g and withdrawal of the spinal fluid after 120 minutes exclusively showed concentrations which were below the identification threshold of the method using 1 micron per millilitre. Patients suffering from subarachnoidal haemorrhages mainly showed a permeation of PAMBA in the cerebrospinal fluid which, however, only rarely reached the lower therapeutically necessary concentration.

4-Aminobenzoic Acid↗

[Asphyxial shock and disseminated intravascular coagulation (DIC) in animal experiments. 3. Secondary fibrinolysis (author's transl)].

In artificially hypoxic rabbit foetuses, rising hydrogen ion concentration with excessive precipitation of fibrin in the microcirculation, with pH values between 7.0 and 6.9, was followed by discontinuation of DIC on account of predominant regular occurrence of secondary fibrinolysis. Such processes of secondary fibrinolysis, which could be inhibited by para-amino methylbenzoic acid (PAMBA), were found to be capable of re-opening completely the circulatory tracks in surviving foetuses. In other cases, they might persist beyond death and cover up pathologico-anatomic findings, if neglected.

4-Aminobenzoic Acid↗

A new method of testing pancreatin therapy in vivo by the use of a peroral chymotrypsin substrate 4-(N-acetyl-L-tyrosyl)aminobenzoic acid.

The efficacy of pancreatin in vivo was determined in 14 patients with advanced pancreatic insufficiency using a peroral test with 2 g of chymotrypsin substrate, 4-(N-acetyl-L-tyrosyl)aminobenzoic acid, the Lundh test meal and 1000 ml tea. Chymotrypsin hydrolysis was quantified by 4-aminobenzoic acid excreted in 6-hr or 8-hr urine samples. After a control test without pancreatin, one or two tablets of Panpur (Nordmark-700 mg of pancreatin and 50 mg of bile per tablet) were applied simultaneously with the Lundh meal on repeated examinations. The urinary excretion of 4-aminobenzoic acid was restored to normal values in 5 subjects during both sampling periods. With this method, stimulated and substituted chymotrypsin is measured at the same time. The conditions of the tests, both with and without pancreatin replacement, are fully comparable and thus the significance of factors modifying the activity of enzymic components in the digestive tube is limited. The method appears appropriate for the institution of an effect pancreatin therapy and its control in vivo.

4-Aminobenzoic Acid↗

Urinary PABA recovery after oral N-benzoyl-L-tyrosyl-PABA administration combined with various exocrine pancreatic stimulants.

Eleven healthy volunteers (C) and nine patients affected by chronic relapsing pancreatitis (CP) were administered N-Benzoyl-L-Tyrosyl-PABA orally, at a dose of 150 mg combined, on different days, with: 1) water alone (schedule a); 2) Lundh meal (schedule b); 3) Secretin-Caerulein by i.v. infusion (0.5 CU/kg/hr and 75 ng/kg/hr respectively) (schedule c); 4) Caerulein by i.m. injection (300 ng/kg) (schedule d). The mean urinary PABA recovery in CP was lower than in C with all the schedules, but this was statistically significant only with schedules a and c (P less than 0.02 and P less than 0.05 respectively). With respect to b, c, and d, the mean urinary PABA recovery seemed to increase both in C and in CP as compared with schedule a, but only in the CP group with schedule b was the increase statistically significant (P less than 0.05). The present data show that the exocrine pancreatic stimulants do not improve the reliability of the PABA test.

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