Biofluid metabonomics using (1)H NMR spectroscopy: the road to biomarker discovery in gastroenterology and hepatology.

Metabolic profiling or 'metabonomics' is an investigatory method that allows metabolic changes associated with the presence of an underlying pathological process to be investigated. Various biofluids can be utilized in the process but urine, serum and fecal extract are most pertinent to the investigation of gastrointestinal and hepatological disease. Nuclear magnetic resonance spectroscopy-based metabonomic research has the potential to generate novel noninvasive diagnostic tests, based on biomarkers of disease, which are simple and cost effective yet retain high sensitivity and specificity characteristics. The process involves a number of key steps, including sample collection, data acquisition, chemometric techniques and, finally, validation. This technique-driven review aims to demystify the metabonomics pathway, while also illustrating the potential of this technique with recent examples of its application in hepato-gastroenterological disease.

Different patterns in immunoreactive anionic and cationic trypsinogen in urine and serum in human acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) results in elevated concentrations of trypsinogen (T) isoenzymes in serum. Immunoreactive anionic trypsinogen in urin (irAT/u) is elevated in AP, and has recently been proposed as a rapid diagnostic instrument and severity predictor. These results have not been confirmed by other groups, and irAT/u has not been further characterized. The concentration of immunoreactive cationic trypsinogen in urine (irCT/u) and the serum irAT/irCT ratio in AP have not been extensively examined. METHODS: Levels of irAT and irCT were studied in urine and serum from 50 AP patients and in urine from 41 non-AP patients. Severity was assessed according to the Atlanta classification. irAT/u was characterized by gel filtration. RESULTS: Gel filtration revealed only AT in the urine. Highly significant differences in irAT/u were seen between AP/non-AP (p < 0.0001) and mild/severe disease (p = 0.0012). The irAT/irCT ratio in serum changed from normal 0.8 to 1.3 in AP. CONCLUSIONS: IrAT and only traces of irCT were found in the urine in AP. IrAT/u was higher in AP than in other acute abdominal disorders (non-AP) and also higher in severe than in mild AP. IrAT in serum (irAT/s) increased proportionally more than irCT/s in AP, but did not discriminate mild from severe forms. High levels of irAT/u in some non-AP cases and a wide range in AP cases make the clinical value of the test questionable.

Sucrose permeability as a means of detecting diseases of the upper digestive tract.

The healthy gastric epithelium will not allow easy permeation of a disaccharide-sized molecule such as sucrose. However, during gastric damage, intact sucrose can pass the gastric epithelium and ultimately appear in the urine. We examined the relationship between total urinary sucrose excretion and various diseases. We used 149 patients (105 had upper gastrointestinal disease, 12 had gastric cancer and 32 were normal). Subjects were given a solution containing 100 g sucrose in 450 c.c. water. All urine was collected for 7.5 h. The urinary sucrose concentration was determined by anion exchange high-performance liquid chromatography. Total urinary sucrose excretion was significantly higher in patients with gastric ulcer and those with gastric cancer than in endoscopically normal controls. In the 34 patients with gastric ulcer, the total sucrose excretion was closely correlated with ulcer size. Ulcer location did not affect urinary sucrose excretion. A strong correlation was also observed between sucrose excretion and lesion size in the 12 patients with gastric cancer. The sucrose permeability test may be a relatively sensitive method to detect gastric disease.

Incidencia de enfermedades digestivas en 784 gestantes / incidence of digestive diseases in 784 pregnant women

Se realizó este estudio prospectivo, en 784 gestantes atendidas en la consulta externa del Departamento de Gineco-Obstetricia del Hospital Cayetano Heredia de Lima, en los meses de Febrero y Marzo de 1990, con la finalidad de conocer la incidencia de enfermedades digestivas asociadas al embarazo y aportar con algunas pautas en su manejo terapéutico. En todos los casos, se realizaron exámenes de laboratorio, ecografías abdominal y pélvica, y en los casos atribuibles a Reflujo gastroesofágico, fueron sometidas al exámen endoscópico digestivo alto. Los resultados fueron: 73 casos, de las 784 gestantes (9.3 por ciento), presentaban dolencias digestivas. De estos 73 casos, se hallaron: estreñimiento en 49 casos (67.1 por ciento), reflujo gastroesofágico 12 casos (16.4 por ciento); hiperemesis gravídica 11 casos (15 por ciento), y pancreatitis aguda un caso (1.3 por ciento). No se detectaron casos con enfermedades hepáticas. Los 12 casos con reflujo gastroesofágico, fueron tratados con dieta y suspención oral que contenian antiácidos y alginato de magnesio. En 10 de estos casos, se obtuvo buena respuesta terapéutica. La endoscopía digestiva brindó efectividad diagnóstica, sin ninguna complicación obstétrica. El estudio mostró una incidencia habitual de estas enfermedades en el embarazo; las que en su mayor parte no son de grado severo; salvo las Pancreatitis agudas, que en nuestro caso evolucionó favirablemente. Las enfermedades hepáticas no detectables en este grupo de gestantes, si constituyen en ciertos casos, problemas en su manejo terapéutico. Ha de ser interesante desarrollar estudios similares en el futuro para confirmar estos resultados, en poblaciones de gestantes de Lima y otras ciudades del Perú.

[Clinical significance of urinary N-acetyl-beta-D-glucosaminidase activities in surgery].

Urinary N-acetyl-beta-D-glucosaminidase (U-NAG) activities were measured in 62 patients surgically treated in our clinic. The results obtained were as follows: The preoperative U-NAG activities were 9.53 +/- 8.63 IU/day in patients in elective operations, and 31.39 +/- 23.47 IU/day in cases in emergency surgery or exploratory laparotomies. The U-NAG activities were elevated slightly even in patients with no postoperative complications, suggesting there was significant damage to the renal tubular epithelium. In the patients with postoperative complications, the U-NAG activities were elevated markedly, especially in those with circulatory shock, suggesting severe damage to the renal tubular epithelium. Though the U-NAG showed abnormally high activities, the values of BUN, S-Cr, U-protein, UUN/BUN, FENa, Ccr, CH2O remained within the normal range. On the contrary, when they were abnormal, the U-NAG activities were not elevated. All patients, who showed high U-NAG activities with abnormal values of Ccr and/or CH2O, developed acute renal failure (ARF). In order to detect ARF in an early stage, Ccr and CH2O should be measured when U-NAG activities rose to over 50 IU/day.