alpha-chymotrypsin and Weight-Loss

The authors previously demonstrated that unconjugated bilirubin (UCB) may inhibit the activities of various digestive proteases, including trypsin and chymotrypsin. The digestive proteases in the lower gut are important in the pathogenesis of inflammatory bowel diseases. The effects of UCB on the inflammation and levels of digestive proteases in feces of rats with colitis have not yet been revealed. The present study investigated the effect of UCB on the inflammatory status and levels of trypsin and chymotrypsin in the feces of rats with trinitrobenzenesulfonic acid (TNBS)‑induced colitis. The data indicated that treatment with TNBS resulted in a marked reduction in weight gain, which was significantly alleviated in UCB‑treated rats. Furthermore, UCB treatment alleviated the inflammation induced by TNBS, detected via macroscopic damage and microscopic inflammation scores, and pro‑inflammatory markers including myeloperoxidase (MPO), tumor necrosis factor (TNF)‑α and interleukin (IL)‑1β. Furthermore, rats with colitis demonstrated significant increases in fecal trypsin and chymotrypsin levels, whereas UCB treatment significantly alleviated these increases. A significant positive correlation was additionally revealed among the pro‑inflammatory markers (MPO, TNF‑α and IL‑1β) and fecal digestive proteases (trypsin and chymotrypsin) in colitis. The results of the present study demonstrated that UCB ameliorated the inflammation and digestive protease increase in TNBS-induced colitis.

Topics: Animals; Bilirubin; Biomarkers; Chymotrypsin; Colitis; Colon; Cytokines; Digestion; Endopeptidases; Feces; Inflammation; Inflammation Mediators; Male; Rats, Sprague-Dawley; Trinitrobenzenesulfonic Acid; Trypsin; Weight Loss

The potential for inhibitors of nuclear factor-kappaB (NF-kappaB) activation to act as inhibitors of muscle protein degradation in cancer cachexia has been evaluated both in vitro and in vivo. Activation of NF-kappaB is important in the induction of proteasome expression and protein degradation by the tumour factor, proteolysis-inducing factor (PIF), since the cell permeable NF-kappaB inhibitor SN50 (18 microM) attenuated the expression of 20S proteasome alpha-subunits, two subunits of the 19S regulator MSS1 and p42, and the ubiquitin-conjugating enzyme, E2(14k), as well as the decrease in myosin expression in murine myotubes. To assess the potential therapeutic benefit of NF-kappaB inhibitors on muscle atrophy in cancer cachexia, two potential inhibitors were employed; curcumin (50 microM) and resveratrol (30 microM). Both agents completely attenuated total protein degradation in murine myotubes at all concentrations of PIF, and attenuated the PIF-induced increase in expression of the ubiquitin-proteasome proteolytic pathway, as determined by the 'chymotrypsin-like' enzyme activity, proteasome subunits and E2(14k). However, curcumin (150 and 300 mg kg(-1)) was ineffective in preventing weight loss and muscle protein degradation in mice bearing the MAC16 tumour, whereas resveratrol (1 mg kg(-1)) significantly attenuated weight loss and protein degradation in skeletal muscle, and produced a significant reduction in NF-kappaB DNA-binding activity. The inactivity of curcumin was probably due to a low bioavailability. These results suggest that agents which inhibit nuclear translocation of NF-kappaB may prove useful for the treatment of muscle wasting in cancer cachexia.

Topics: Animals; Blood Proteins; Cachexia; Cells, Cultured; Chymotrypsin; Curcumin; Electrophoretic Mobility Shift Assay; Enzyme Activation; Enzyme Inhibitors; I-kappa B Proteins; Male; Mice; Mice, Inbred Strains; Muscle Fibers, Skeletal; Muscle, Skeletal; Neoplasms, Experimental; NF-kappa B; NF-KappaB Inhibitor alpha; Proteasome Endopeptidase Complex; Proteoglycans; Resveratrol; Stilbenes; Ubiquitins; Weight Loss

To investigate the state of activation of the ATP-ubiquitin-dependent proteolytic system in the skeletal muscle of gastric cancer patients.. Muscle wasting in experimental cancer cachexia is frequently associated with hyperactivation of the ATP-dependent ubiquitin-proteasome proteolytic system. Increased muscle ubiquitin mRNA levels have been previously shown in gastric cancer patients, suggesting that this proteolytic system might be modulated also in human cancer.. Biopsies of the rectus abdominis muscle were obtained intraoperatively from 23 gastric cancer patients and 14 subjects undergoing surgery for benign abdominal diseases, and muscle ubiquitin mRNA expression and proteasome proteolytic activities were assessed.. Muscle ubiquitin mRNA was hyperexpressed in gastric cancer patients compared to controls. In parallel, three proteasome proteolytic activities (CTL, chymotrypsin-like; TL, trypsin-like; PGP, peptidyl-glutamyl-peptidase) significantly increased in gastric cancer patients with respect to controls. Advanced tumor stage, poor nutritional status, and age more than 50 years were associated with significantly higher CTL activity but had no influence on TL and PGP activity.. These results confirm the involvement of the ubiquitin-proteasome proteolytic system in the pathogenesis of muscle protein hypercatabolism in cancer cachexia. The observation that perturbations of this pathway in gastric cancer patients occur even before clinical evidence of body wasting supports the thinking that specific pharmacologic and metabolic approaches aimed at counteracting the upregulation of this pathway should be undertaken as early as cancer is diagnosed.

Topics: Biopsy; Chymotrypsin; Cysteine Endopeptidases; Endopeptidases; Female; Gene Expression; Humans; In Vitro Techniques; Male; Middle Aged; Multienzyme Complexes; Nutritional Status; Proteasome Endopeptidase Complex; Rectus Abdominis; RNA, Messenger; Stomach Neoplasms; Trypsin; Ubiquitin; Weight Loss

The aim of this study was to determine the prevalence of steatorrhea in patients with Graves' disease and to assess its significance and correlation with changes in body mass index (BMI), coefficient of fat absorption (COFA), and pancreatic exocrine function in these patients.. Daily dietary fat intake, 24 h fecal fat, COFA, fecal chymotrypsin activity (as an index of pancreatic exocrine function), and total T3, T4, and TSH levels were assessed in 28 patients with active Graves' disease. In 24 patients, reassessment was done after attaining a euthyroid state with carbimazole therapy.. In the thyrotoxic state, 13 of 28 patients had steatorrhea, whereas 15 had normal (<6 g/day) fat excretion (11.4 +/- 6.7 g vs 2.9 +/- 0.8 g, p = 0.0007). Daily fat intake, basal BMI, and serum T3 and T4 levels were similar in the steatorrheic and nonsteatorrheic groups. The mean COFA of the steatorrheic group was significantly lower than that of nonsteatorrheic group (91.6% +/- 4.8% vs 97.7% +/- 0.9%, respectively; p = 0.0006). In the steatorrheic group, fat excretion and COFA normalized after attainment of euthyroidism (changes in fat excretion and COFA = 7.3% +/- 6.3 g/day and 7.7% +/- 5.4%, respectively). Fecal chymotrypsin levels were similar in the steatorrheic and nonsteatorrheic thyrotoxics and in 16 healthy control subjects. The levels did not show any significant changes following attainment of euthyroid status.. Steatorrhea associated with a decrease in COFA can occur in a reversible manner in 46% of patients with Graves' disease. However, steatorrhea in these patients is not linked with weight loss or with pancreatic exocrine dysfunction.

Topics: Absorption; Adult; Antithyroid Agents; Body Mass Index; Carbimazole; Case-Control Studies; Celiac Disease; Chymotrypsin; Dietary Fats; Feces; Female; Follow-Up Studies; Graves Disease; Humans; Lipids; Male; Pancreas; Prevalence; Thyrotoxicosis; Thyrotropin; Thyroxine; Triiodothyronine; Weight Loss

The determination of faecal pancreatic elastase 1 is a reliable test for the diagnosis of chronic pancreatic diseases in man due to its high sensitivity and specificity (93%). A clinical study was performed to investigate the detectability of canine faecal pancreatic elastase with polyclonal anti human pancreatic elastase 1 antibodies in 52 dogs with chronic diarrhoea and weight loss. To assess the diagnostic value of this parameter for the diagnosis of exocrine pancreatic insufficiency (EPI) in dogs faecal chymotrypsin activity was determined and serum trypsin-like immunoreactivity (TLI) concentration was measured within the Ceruletid test in all patients. The study revealed that canine faecal pancreatic elastase cross reacts with polyclonal anti human pancreatic elastase 1 antibodies. In comparison with the results of the other pancreas tests it was proved that the concentration of canine faecal pancreatic elastase determined by rocket immunoelectrophoresis is highly sensitive for EPI in dogs (sensitivity 100%) but there are species differences in specificity between man and dog (specificity 56.5%).

Topics: Animals; Antibodies; Chronic Disease; Chymotrypsin; Diarrhea; Dog Diseases; Dogs; Feces; Humans; Immunoelectrophoresis; Pancreatic Diseases; Pancreatic Elastase; Predictive Value of Tests; Sensitivity and Specificity; Trypsin; Weight Loss

In 96 consecutive patients who underwent a 72-h faecal fat determination because of suspected nutrient malassimilation (maldigestion and/or malabsorption) faecal chymotrypsin (F-Chym) was estimated with a commercial photometric test (Monotest Chymotrypsin), comparing F-Chym concentrations in the first 24-h stool with the total 72-h F-Chym output. In the first 24-h faeces, the F-Chym concentration, calculated as a mean of three random samples, did not significantly differ from a single value obtained after homogenization. In known pancreatic disease, a F-Chym concentration less than 3.0 U/g wet faeces distinguished well between steatorrhoic patients (n = 12) and nonsteatorrhoic (n = 13) (positive predictive value (PV), 91%; negative PV, 86%) but was less suitable as a screening test for pancreatic steatorrhoea in the unselected patient group (positive PV, 61%; negative PV, 98%). Although the estimation of 72-h F-Chym output could differentiate between various subgroups of patients to a certain extent, the positive PV for discovery of pancreatic steatorrhoea in a single patient was low. Four patients had excessively high F-Chym output and increased bile acid excretion after ileal resection (n = 3) and radiation ileitis (n = 1), respectively, possibly indicating the removal of an inhibitory mechanism of pancreatic and biliary secretion in these conditions.

Topics: Adult; Celiac Disease; Chymotrypsin; Exocrine Pancreatic Insufficiency; Feces; Female; Humans; Intestinal Diseases; Male; Middle Aged; Postgastrectomy Syndromes; Predictive Value of Tests; Sensitivity and Specificity; Weight Loss