alpha-chymotrypsin and Skin-Diseases

Does prophylactic treatment with proteolytic enzymes reduce acute toxicity of adjuvant pelvic radiotherapy?. Fifty-six patients with an indication for adjuvant pelvic irradiation after curative surgery were double-blind randomized. All patients took 3 x 4 capsules study medication daily during radiotherapy. Twenty-eight patients in the enzyme group (EG) received capsules containing papain, trypsin and chymotrypsin, 28 in the placebo group (PG) received placebo capsules. All patients were irradiated with 5 x 1.8 Gy weekly to 50.4 Gy using four-field-box technique after CT-based planning. Primary objective was the grade of diarrhea, nausea, vomiting, fatigue and epitheliolysis during radiotherapy. Secondary objectives were the number of supportive medications and treatment interruptions due to acute toxicity.. None/mild diarrhea: 43% EG, 64% PG. Moderate/severe diarrhea: 57% EG, 36% PG (P = 0.11). Mean duration: 11 days in EG, 10 days in PG. None/mild nausea: 93% EG, 93% PG. Moderate/severe nausea: 7% EG, 7% PG. None/mild vomiting: 100% EG, 97% PG. None/mild fatigue: 82% EG, 93% PG. Moderate/severe fatigue: 18% EG, 7% PG (P = 0.23). None/mild epitheliolysis: 75% EG, 93% PG. Moderate/severe epitheliolysis: 25% EG, 7% PG (P = 0.16). Treatment interruption (mean days): 2.44 in EG, 1.46 in PG. Number of supportive medication: 29 in EG, 19 in PG.. The prophylactic use of proteolytic enzymes does not reduce acute toxicities, treatment interruptions and number of supportive medication and therefore does not improve tolerance of adjuvant pelvic radiotherapy.

Topics: Chymotrypsin; Combined Modality Therapy; Diarrhea; Double-Blind Method; Drug Combinations; Fatigue; Female; Humans; Male; Middle Aged; Nausea; Pancreatic Extracts; Papain; Pelvic Neoplasms; Peptide Hydrolases; Radiation Injuries; Radiotherapy, Adjuvant; Skin Diseases; Thymus Extracts; Treatment Outcome; Trypsin; Vomiting

In xerotic skin, the proteolysis of desmosomes is reduced leading to the accumulation of corneocytes on the surface of the skin. The effect of proteases applied topically to soap-induced xerotic skin was evaluated using a five-point visual scale. The visual scaling associated with soap-induced xerosis could be ameliorated by the topical application of exogenous protease. Bovine pancreatic chymotrypsin, papain, and a bacterial protease from Bacillus licheniformis were all capable of facilitating the reduction in visual scaling in a short time. Alcalase and Optimase, both broad specificity alkaline bacterial proteases, were the most weight-efficient at delivering this clinical effect. The reduction in scaling could be achieved either by occluded application of an aqueous enzyme solution or by a two-step unoccluded application first of an aqueous enzyme solution followed by a commercial moisturizer. Morphological and immunological analysis of bacterial enzyme-treated skin revealed that topically applied protease specifically induced the degradation of the desmosomes thereby promoting desquamation. These results indicate that topical application of protease can significantly and rapidly reduce the visual scaling associated with soap-induced xerosis by promoting desmosome degradation within the corneocyte clumps.

Topics: Administration, Topical; Adult; Animals; Chymotrypsin; Double-Blind Method; Humans; Middle Aged; Papain; Serine Endopeptidases; Skin; Skin Diseases; Soaps; Substrate Specificity; Subtilisins; Swine

Increased activity of matrix metalloproteinase-9 (MMP-9) has been well documented in many diseases associated with inflammation, such as chronic wounds, bullous pemphigoid, liver failure, and tumor metastases. The mechanism for the proteolytic activation of pro-MMP-9 in human tissue still remains unknown.. We investigated this mechanism through reconstitution of an inflammatory condition in normal human skin, and epidermal and dermal cells derived from skin. Normal human skin was cultured with exogenous cytokines associated with inflammation and tissue repair. MMP-9 induction and activation were measured, and potential mechanisms were probed by inhibitors.. Pathophysiologic concentrations of interleukin (IL)-1alpha rapidly induced pro-MMP-9 synthesis by human skin. In contrast, IL-1-induced activation of pro-MMP-9 was a slow process, which required 3 days. Tumor growth factor-beta induced pro-MMP-9 but failed to promote activation of the precursor. When the skin was stimulated with the combination of tumor growth factor-beta and IL-1alpha, substantial induction and activation of pro-MMP-9 occurred. This IL-1 induced activation of pro-MMP-9 was observed in intact skin but not in isolated dermal fibroblasts or keratinocytes. IL-1-induced activation of pro-MMP-9 was inhibited by chymostatin, a chymotrypsinlike proteinase inhibitor. Furthermore, IL-1alpha decreased tissue inhibitor of metalloproteinase 1 without changing MMP-9 activator activity.. The proteolytic activation of pro-MMP-9 in skin inflammatory diseases likely occurs via a pathway including IL-1alpha. The activation is mediated by downregulation of tissue inhibitor of MMP-1 and involves an as yet unidentified chymotrypsinlike proteinase.

Topics: Chymotrypsin; Collagenases; Dermis; Down-Regulation; Enzyme Activation; Enzyme Precursors; Fibroblasts; Humans; Interleukin-1; Keratinocytes; Matrix Metalloproteinase 9; Organ Culture Techniques; Signal Transduction; Skin Diseases; Tissue Inhibitor of Metalloproteinase-1

Topics: alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Animals; Chymotrypsin; Histiocytes; Humans; Immunoenzyme Techniques; Muramidase; Rabbits; Skin Diseases; Swine; Trypsin Inhibitors

Trypsin and chymotrypsin concentrations were determined in 180 spot stool specimens from 110 control patients in hospital. The lower limit of normality for each enzyme was placed at the 5% level: 95% of this population excreted feces containing more than 100 mug. of chymotrypsin and 30 mug. of trypsin per g. of feces. Chymotrypsin concentrations appeared to be a more reliable guide to pancreatic function than trypsin concentrations.Fecal chymotrypsin concentrations were subnormal in five patients with chronic pancreatitis, borderline in one patient with relapsing pancreatitis, subnormal in one patient after pancreatectomy, and subnormal in five of nine with carcinoma of the pancreas. Subnormal concentrations of fecal chymotrypsin were found in seven of 21 patients with chronic liver disease related to alcoholism, eight of 32 with a partial gastrectomy, three of 10 with adult celiac disease and five of 16 with psoriasis.It appears that the determination of fecal chymotrypsin concentrations provides a valuable screening test for pancreatic exocrine deficiency. However, normal results may be found in some patients with pancreatic disease and subnormal values may occur in some patients with other conditions.

Topics: Alcoholism; Chymotrypsin; Feces; Humans; Liver Cirrhosis; Malabsorption Syndromes; Pancreatic Diseases; Pancreatic Neoplasms; Pancreatitis; Skin Diseases; Trypsin

Topics: Biomedical Research; Chymotrypsin; Humans; Hyaluronoglucosaminidase; Hypothermia; Hypothermia, Induced; Injections; Injections, Intradermal; Lidocaine; Pharmacology; Psoriasis; Skin Diseases; Sutures; Wounds and Injuries

Topics: Adult; Chymotrypsin; Endopeptidases; Humans; Middle Aged; Skin; Skin Diseases; Trypsin

Topics: Administration, Topical; Adolescent; Adult; Anti-Inflammatory Agents; Chymotrypsin; Female; Humans; Hydrocortisone; Male; Middle Aged; Neomycin; Skin Diseases

Topics: Angioedema; Chymotrypsin; Diuretics; Drug Therapy; Eczema; Humans; Leg; Lymphedema; Phlebitis; Skin Diseases; Varicose Veins; Wounds and Injuries

Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Chymotrypsin; Foot Diseases; Humans; Hydrocortisone; Neomycin; Ointments; Podiatry; Skin Diseases

Topics: Chymotrypsin; Foot Diseases; Hematologic Tests; Humans; Injections, Intradermal; Skin Diseases

Topics: Chymotrypsin; Humans; Hydrocortisone; Neomycin; Ointments; Skin Diseases

Topics: Chymotrypsin; Dermatitis; Humans; Hydrocortisone; Neomycin; Ointments; Pyoderma; Skin Diseases

Topics: Chymotrypsin; Dermatology; Hematologic Tests; Humans; Skin Diseases