Vanillin Analog - Vanillyl Mandelic Acid, a Novel Specific Inhibitor of Snake Venom 5′-Nucleotidase

2014 ◽  
Vol 347 (9) ◽  
pp. 616-623 ◽  
Author(s):  
Raghaven Arun ◽  
Abdul Salam Syed Yasir Arafat ◽  
Cletus J. M. D'Souza ◽  
Venkatabalasubramanian Sivaramakrishnan ◽  
Bhadrapura Lakkappa Dhananjaya
1968 ◽  
Vol 43 (229) ◽  
pp. 372-376 ◽  
Author(s):  
N. Matsaniotis ◽  
N. Beratis ◽  
C. Economou-Mavrou

1981 ◽  
Author(s):  
F S Markland ◽  
E Shaw ◽  
C Kettner ◽  
S Schiffman ◽  
S S Bajwa ◽  
...  

During amino acid sequence determination of crotalase, a thrombin-like enzyme from Crotalus adamanteus (eastern diamondback rattlesnake) venom, we found that in addition to the expected structural homology with bovine thrombin, there was even greater homology with porcine pancreatic kallikrein. In exploring further the similarity between crotalase and kallikrein, several completely unexpected and interesting observations were made. First, crotalase was rapidly and specifically inhibited by the tripeptide, affinity-labelling chloromethyl ketone inhibitor Pro-Phe-Arg-CH2Cl, which is known to be a specific inhibitor of urinary kallikrein. Further, crotalase exhibits significant activity not only with the thrombin chromogenic substrate S-2238 (H-D-Phe- pipecolyl-Arg-p-nitroanilide) and the general serine protease substrate S-2160 (N-benzoyl-Fhe-Val-Arg-p-nitroanilide) but also with the plasma kallikrein substrate S-2302 (H-D- Pro-Phe-Arg-p-nitroanilide) and the glandular kallikrein substrate S-2266 (H-D-Val-Leu-Arg-p-nitroanilide). Additionally, SDS polyacrylamide gel electrophoresis reveals that crotalase cleaves the plasma kallikrein susceptible bonds in human high molecular weight kiniogen (HMWK) producing intermediates with procoagulant activity. Analyses for bradykinin release from HMWK are presently in progress. Interestingly, one of the normal activities of plasma kallikrein, the activation of human plasminogen, was not one of the activities possessed by crotalase.In summary, it would appear that crotalase has significant kallikrein-like activity. Whether this will prove to be of importance in the ongoing clinical application of fibrinogen clotting snake venom enzymes, such as ancrod and batroxobin, remains to be shown.


2007 ◽  
Vol 92 (12) ◽  
pp. 4602-4608 ◽  
Author(s):  
James G. Boyle ◽  
D. Fraser Davidson ◽  
Colin G. Perry ◽  
John M. C. Connell

Abstract Context: Recent evidence suggests that plasma-free metanephrines provide a highly sensitive test in patients requiring exclusion of pheochromocytoma. The diagnostic efficacy of urinary free metanephrines, however, has not been evaluated. Objective, Design, Setting, Patients, and Outcome Measures: We compared retrospectively the diagnostic efficacy of 24-h urinary free metanephrines with our currently available measurements of 24-h urinary vanillyl mandelic acid (VMA), urinary catecholamines, and plasma catecholamines in 159 outpatients tested in a tertiary referral center for pheochromocytoma over a 4-yr period. Results: The sensitivity of urinary free metanephrines was 100% [25 of 25 patients; 95% confidence interval (CI) 86–100%)] compared with the sensitivity of 84% (21 of 25; 95% CI 64–95%) for urinary catecholamines; 72% (18 of 25; 95% CI 51–88%) for urinary VMA; and 76% (16 of 21; 95% CI 53–92%) for plasma catecholamines. The specificity of urinary free metanephrines was 94% (116 of 123; 95% CI 89–98%), compared with the specificity of 99% (127 of 129; 95% CI 96–100%) for urinary catecholamines; 96% (130 of 134; 95% CI 91–98%) for urinary VMA; and 88% (66 of 75; 95% CI 78–94%) for plasma catecholamines. Receiver operating characteristic curves for all test groups were generated. Pairwise comparisons of the area under the receiver operating characteristic curve for urinary free metanephrines with that of each of the other three test groups individually were: 0.993 (95% CI 0.962–0.999) vs. 0.919 (95% CI 0.862–0.957, P = 0.032) for urine catecholamines; 0.993 (95% CI 0.962–0.999) vs. 0.846 (95% CI 0.778–0.900, P = 0.002) for urine VMA; and 0.992 (95% CI 0.945–0.998) vs. 0.852 (95% CI 0.762–0.918, P = 0.009) for plasma catecholamines. Testing with urinary free metanephrines failed to misidentify a single case of pheochromocytoma, compared with four missed cases for urinary catecholamines, seven missed cases for urinary VMA, and five missed cases for plasma catecholamines. Conclusion: Urinary free metanephrines were superior to urinary VMA, urinary catecholamines, and plasma catecholamines and can provide a valuable test for diagnosis of pheochromocytoma in adults.


1974 ◽  
Vol 41 (5) ◽  
pp. 567-572 ◽  
Author(s):  
Bruce O. Berg ◽  
Arthur R. Ablin ◽  
Winfred Wang ◽  
Rayburn Skoglund

✓ The authors report four cases of occult neuroblastoma in children with the striking clinical findings of opsoclonus, myoclonus, and ataxia. The diagnostic value of plain roentgenograms of the chest and abdomen or an intravenous pyelogram is emphasized. Assays for vanillyl mandelic acid and cystathionine may be of value. The clinical course and pathogenesis of encephalopathies due to neuroblastoma are discussed.


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