Practical Interpretation and Application of Exocrine Pancreatic Testing in Small Animals.

The pancreas remains a difficult organ to evaluate using laboratory methods alone. No single laboratory test is diagnostic of pancreatitis (chronic or acute) without other diagnostic modalities concurring with the diagnosis or ruling out other diseases. The diagnosis of pancreatitis is particularly difficult in cats, and pancreatitis often occurs with other diseases. The use of pancreatic cytology may be useful in diagnosing both inflammation and neoplasia. Exocrine pancreatic insufficiency (EPI) can be relatively easily diagnosed when clinically manifested by the measurement of trypsinlike immunoreactivity. Diagnosis is more difficult when EPI is subclinical.

Methods for measuring proteasome activity: current limitations and future developments.

The proteasome has been validated as a therapeutic target, with proteasome inhibitors showing particular efficacy in the treatment of Multiple Myeloma. A wide range of methods have been developed to profile proteasome activity. These include the current method of choice fluorogenic peptide substrates, as well as bioluminescent imaging, immunological methods, and more recently, site-specific fluorescent probes. The aim of this review is to evaluate the currently available methods for profiling proteasome activity and their suitability for use in translational studies. Ongoing development of techniques for profiling proteasome activity will facilitate future research into proteasome-related pathologies, thus accelerating the development of more specific drug regimes.

Muscular exercise can cause highly pathological liver function tests in healthy men.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: The occurrence of idiosyncratic drug hepatotoxicity is a major problem in all phases of clinical drug development and the leading cause of postmarketing warnings and withdrawals. Physical exercise can result in transient elevations of liver function tests. There is no consensus in the literature on which forms of exercise may cause changes in liver function tests and to what extent. WHAT THIS STUDY ADDS: Weightlifting results in profound increases in liver function tests in healthy men used to moderate physical activity, not including weightlifting. Liver function tests are significantly increased for at least 7 days after weightlifting. It is important to impose relevant restrictions on heavy muscular exercise prior to and during clinical studies. AIM: To investigate the effect of intensive muscular exercise (weightlifting) on clinical chemistry parameters reflecting liver function in healthy men. METHODS: Fifteen healthy men, used to moderate physical activity not including weightlifting, performed an 1 h long weightlifting programme. Blood was sampled for clinical chemistry parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LD), gamma-glutamyl transferase (gamma GT), alkaline phosphatase (ALP), bilirubin, creatine kinase (CK) and myoglobin] at repeated intervals during 7 days postexercise and at a follow-up examination 10-12 days postexercise. RESULTS: Five out of eight studied clinical chemistry parameters (AST, ALT, LD, CK and myoglobin) increased significantly after exercise (P < 0.01) and remained increased for at least 7 days postexercise. Bilirubin, gamma GT and ALP remained within the normal range. CONCLUSION: The liver function parameters, AST and ALT, were significantly increased for at least 7 days after the exercise. In addition, LD and, in particular, CK and myoglobin showed highly elevated levels. These findings highlight the importance of imposing restrictions on weightlifting prior to and during clinical studies. Intensive muscular exercise, e.g. weightlifting, should also be considered as a cause of asymptomatic elevations of liver function tests in daily clinical practice.

Utilidad clínica de la elastasa polimorfonuclear en las pancreatitis agudas / Clinical utility of polymorphonuclear elastase in acute pancreatitis

Introducción. La elastasa polimorfonuclear es una proteasa localizada en los lisosomas de los leucocitos polimorfonucleares que se libera como mecanismo de defensa para eliminar los productos de degradación tisular en el lugar de la inflamación. En este trabajo se evalúa la utilidad de la determinación de la elastasa como factor pronóstico en pacientes con pancreatitis aguda. Pacientes y método. Se realiza un estudio prospectivo sobre la utilidad de la medida de la elastasa en una serie de 31 pacientes con pancreatitis aguda. Se les efectuó, dentro de los primeros 3 días del ingreso hospitalario, la determinación de hemograma, bioquímica, elastasa polimorfonuclear y proteína C reactiva, además de la evaluación clínica -mediante criterios de Ranson- como grave y leve. Resultados. Se ha encontrado una serie de 7 pacientes con una elastasa media (ñ DE) de 301 ñ 277 µg/l y proteína C reactiva de 14,3 ñ 17,1 mg/dl, que se asocian a una evolución tórpida. En los otros 24 pacientes, la elastasa fue 109 ñ 115 µg/l, y proteína C reactiva de 4,84 ñ 5,87 mg/dl, presentando una evolución favorable. Conclusiones. Existen diferencias significativas entre los dos grupos en ambos parámetros. Tanto la elastasa polimorfonuclear como la proteína C reactiva, junto con otros datos clínicos y el recuento leucocitario, constituyen unos parámetros útiles para diferenciar las pancreatitis agudas graves de las leves (AU)

Finding and using hyperthermophilic enzymes.

Recent developments have enhanced the prospects for the discovery of hyperthermophilic enzymes. This is important because the intrinsic basis underlying the extraordinary thermostability of hyperthermophilic enzymes has yet to be revealed, and so engineering this characteristic into less thermophilic enzymes is not possible at this time. Successful efforts to clone and express the genes encoding hyperthermophilic enzymes in mesophilic hosts have improved the availability of high-temperature biocatalysts. The remaining task is the identification of opportunities to make strategic use of the thermoactivity and thermostability of hyperthermophilic enzymes.