Search

The aggregation of misfolded proteins, such as α-synuclein in Parkinson's disease (PD), occurs intracellularly or extracellularly in the majority of neurodegenerative diseases. The immunoproteasome has more potent chymotrypsin-like activity than normal proteasome. Thus, degradation of α-synuclein aggregation via immunoproteasome is an attractive approach for PD drug development. Herein, we aimed to determine if novel compound, 11-Hydroxy-1-(8-methoxy-5-(trifluoromethyl)quinolin-2-yl)undecan-1-one oxime (named as J24335), is a promising candidate for disease-modifying therapy to prevent the pathological progression of neurodegenerative diseases, such as PD. The effects of J24335 on inducible PC12/A53T-α-syn cell viability and cytotoxicity were evaluated by MTT assay and LDH assay, respectively. Evaluation of various proteasome activities was done by measuring the luminescence of enzymatic activity after the addition of different amounts of aminoluciferin. Immunoblotting and real-time PCR were employed to detect the expression of various proteins and genes, respectively. We also used a transgenic mouse model for behavioral testing and immunochemical analysis, to assess the neuroprotective effects of J24335. J24335 inhibited wild-type and mutant α-synuclein aggregation without affecting the growth or death of neuronal cells. The inhibition of α-synuclein aggregation by J24335 was caused by activation of immunoproteasome, as mediated by upregulation of LMP7, and increased cellular chymotrypsin-like activity in 20S proteasome. J24335-enhanced immunoproteasome activity was mediated by PKA/Akt/mTOR pathway activation. Moreover, animal studies revealed that J24335 treatment markedly mitigated both the loss of tyrosine hydroxylase-positive (TH-) neurons and impaired motor skill development. This is the first report to use J24335 as an immunoproteasome enhancing agent to antagonize pathological α-synuclein-mediated neurodegeneration., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Simon Ming-Yuen Lee reports financial support was provided by The Science and Technology Development Fund (FDCT) of Macau SAR. Simon Ming-Yuen Lee reports financial support was provided by Shenzhen-Hong Kong-Macao Science and Technology Innovation Project (Category C) of Shenzhen Science and Technology Innovation Committee. Simon Ming-Yuen Lee reports financial support was provided by University of Macau. Hefeng Zhou reports financial support was provided by Science and Technology Foundation of Guizhou Province. Hefeng Zhou reports financial support was provided by National Natural Science Foundation of China. Min Shao reports financial support was provided by Science and Technology Foundation of Guizhou Province. J24335 was synthesized by Prof. Ji-Wang Chern. The new compound J24335 mentioned in this paper was synthesized by Prof. Ji-Wang Chern's team (including Ji-Wang Chern, Chao-Wu Yu and Qingqing Ye) at National Taiwan University. Prior to conducting this study, our laboratory team had obtained permission from Prof. Chern to perform research on this compound. Therefore, there is no conflict of interest between our team and Prof. Chen's research team., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: The efficacy of trypsin-chymotrypsin in postoperative pain management following single-visit root canal treatment of teeth with symptomatic irreversible pulpitis was evaluated. Additionally, synergistic effects with nonsteroidal anti-inflammatory drugs and reported side effects were also investigated., Methods: This prospective, parallel, triple-blinded phase IV randomized controlled trial included 60 patients with mandibular first molars exhibiting symptomatic irreversible pulpitis. The patients were randomly allocated using computer software to one of four treatment groups (n = 15 each), and either ibuprofen (600 mg), ambezim-G (trypsin 5mg-chymotrypsin 5 mg), a combination of both, or a placebo drug were administered postoperatively. The participants scored pain intensity at different time-intervals using a numerical scale, and passive surveillance of harm was used to detect clinical safety. Age was compared between groups using a one-way analysis of variance test. Pain scores were analyzed using the Kruskal-Wallis and Friedman's tests and, if significant, Dunn's test was used for pairwise comparisons. The chi-square test was used to compare qualitative data, and the significance level was set at P value ≤ .05., Results: All interventions were found to be effective in reducing postoperative pain, and no statistically significant differences were observed between the ibuprofen, trypsin-chymotrypsin, and combination groups. However, all 3 groups differed significantly from the placebo group. The safety profile of the interventions did not differ significantly., Conclusions: Trypsin-chymotrypsin exhibits comparable efficacy to nonsteroidal anti-inflammatory drugs. No synergistic effects occur when the 2 are used in combination. This is the first randomized controlled trial to assess the effects of proteolytic enzymes on postendodontic pain., Trial Registration: clinicaltrials.gov, Identifier: NCT05479747., (Copyright © 2022 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: The Food and Drug Administration in 2006 required that all pancreatic enzyme products demonstrate bioavailability of lipase, amylase, and protease in the proximal small intestine., Methods: In this phase I open-label, randomized, crossover trial, 17 adult chronic pancreatitis (CP) patients with severe exocrine pancreatic insufficiency (EPI) underwent two separate gastroduodenal perfusion procedures (Dreiling tube suctioning and [ 14 C]-PEG instillation by an attached Dobhoff tube in the duodenal bulb). Patients received Ensure Plus® alone and Ensure Plus with Zenpep (75,000 USP lipase units) in random order. The bioavailability of Zenpep was estimated by comparing the recovery of lipase, amylase, chymotrypsin activity in two treatment conditions. 14 C-PEG was used to correct duodenal aspirates volume. The primary efficacy endpoint was lipase delivery in the duodenum after Zenpep administration under fed conditions. Secondary efficacy endpoints included chymotrypsin and amylase delivery, serum CCK levels, and measuring duodenal and gastric pH., Results: Zenpep administration with a test meal was associated with significant increase in duodenal aspiration of lipase (p = 0.046), chymotrypsin (p = 0.008), and amylase (p = 0.001), compared to the test meal alone, indicating release of enzymes to the duodenum. Lipase delivery was higher in the pH subpopulation (the efficacy population with acid hypersecretors excluded) (p = 0.01). Recovery of [ 14 C]-PEG was 61%. Zenpep was generally well tolerated. All adverse events were mild and transient., Conclusions: In CP patients with severe EPI, lipase, chymotrypsin and amylase were released rapidly into the duodenum after ingestion of Zenpep plus meal compared to meals alone. Results also reflected the known pH threshold for enzyme release from enteric coated products., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

This preliminary study aims to investigate the effects of a maximal implant retention procedure. The authors retrospectively reviewed the use of negative pressure wound therapy with chymotrypsin irrigation treating implant infection/exposure in titanium mesh cranioplasty by comparing patients with titanium mesh totally retained, partially removed, or totally removed according to the evaluation during the surgery. Negative pressure wound therapy with chymotrypsin irrigation was applied 5 days after the surgery. The negative pressure was set at -125 to -150 mmHg. A total of 21 patients were included, 4 patients treated with titanium mesh totally removed; 3 patients treated with titanium mesh partially removed; and 14 patients treated with U-shape debridement with titanium mesh preserved completely. However, 1 patient in the U-shape group required a second debridement to remove all implant. Negative pressure wound therapy with chymotrypsin irrigation is a novel procedure and could be used to treat implant-related infection without the exchange of implant.

This article introduces the combined application of vacuum sealing drainage (VSD) and chymotrypsin in the treatment of post-operative mandibular osteomyelitis. The lesion was washed by chymotrypsin (4000U) and saline (500 ml). VSD is effective in the treatment of traumatic mandibular osteomyelitis. This study investigates the effect of VSD combined with chymotrypsin in the treatment of patients with osteomyelitis after mandibular trauma. It is proved that it has a good effect in ensuring drainage, controlling infection and retaining internal fixation, and can create a good environment for fracture healing.

Tissue damage of all types, such as surgical or accidental injuries, fractures, and burns, stimulates a well-orchestrated, physiological process of healing, which ultimately leads to structural and functional restoration of the damaged tissues. The tissue repair process can be broadly divided into four continuous and overlapping phases-hemostasis and coagulation, inflammation, proliferation, and remodeling. If the process is interrupted or halted during any stage, it leads to impaired healing and formation of a chronic wound. Chronic wounds are associated with significant morbidity, mortality, and poor quality of life. Therefore, prompt and effective management of acute tissue injury is necessary to prevent it from progressing to a chronic wound. Proteolytic enzymes have been used to facilitate tissue repair since ancient times. Trypsin:chymotrypsin is an oral proteolytic enzyme preparation which has been in clinical use since the 1960s. It provides better resolution of inflammatory symptoms and promotes speedier recovery of acute tissue injury than several of the other existing enzyme preparations. This review article revisits the role and clinical utility of trypsin:chymotrypsin combination in tissue repair., Funding: Torrent Pharmaceuticals Limited.

Chronic obstructive parotitis (COP) is a common disease of the parotid gland. A total of 104 patients with COP were identified and randomized into a treatment group (52 cases) and a control group (52 cases). All patients underwent sialography and salivary gland scintigraphy (SGS) examinations before surgery. The patients in the treatment group received chymotrypsin combined with gentamicin via interventional sialendoscopy to irrigate the duct, and the control group received gentamicin alone. All patients were asked to record their pain on a visual analogue scale (VAS) before treatment and at 1 week, 2 weeks, 1 month, 3 months, and 6 months after surgery. The VAS score for pain intensity was decreased at 1 week post-treatment in both groups (P<0.05). Compared to the control group, the VAS score was lower in the treatment group at 1 week, 2 weeks, and 1 month post-treatment (P<0.05). The 6-month postoperative SGS results showed improved uptake and excretion in both groups (P<0.05). The treatment group exhibited higher scores for postoperative SGS excretion than the control group (P<0.05). The administration of chymotrypsin combined with gentamicin by sialendoscopy is effective for the treatment of non-stone-related COP and specifically improves the excretion function of the parotid gland., (Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Introduction: Systemic enzyme therapy can play an important role in maintaining normal inflammatory processes within the body and thereby helps support and speed up healing. In the course of the anti-inflammatory action, enzymes degrade damaged cells and necrotic material and, through the inactivation of mediators and toxic products, they restrict the edema and pain., Method: The study conducted at Grant Medical College, Mumbai, India was a clinical trial comparing the efficacy and tolerability of three oral enzyme treatment groups-oral tablets containing trypsin:chymotrypsin (TC) (Chymoral Forte ® ), serratiopeptidase (S) 5 mg oral tablets, and oral enzyme tablets containing trypsin 48 mg, bromelain 90 mg, and rutoside 100 mg (TBR)-to evaluate their healing potential in surgical wounds after orthopedic surgery., Results: A total of 75 patients were screened, randomized, and divided into three groups in 1:1:1 ratio receiving either of the three treatments. In the TC group, erythema was significantly reduced from 3.44 on day 3 to 1.16 on day 10 (p < 0.01). There was significantly better reduction in erythema scores in the TC group as compared to S and TBR groups (p < 0.05) at each follow-up visit. Similarly reduction in the local irritation, wound discharge, edema, induration, and tenderness score with TC treatment at the end of the study was significantly higher than that observed in the other two groups. In addition TC showed significant reduction in pain on the VAS scale (p < 0.01). Global assessment of response to therapy for efficacy and tolerability was reported to be good to excellent in 88% and 92% of the patients on TC as compared to 12% and 8% with S and 12% and 8% with TBR., Conclusion: TC provides a better resolution of symptoms of inflammation after orthopedic surgery as compared to S and TBR, thus facilitating better wound healing. Further studies are warranted to confirm the findings., Trial Registration: Clinical Trial Registry of India (Reg. No. CTRI/2011/07/001920).

This study was undertaken to investigate the effect of α-chymotrypsin on methyl nitrosourea (MNU) induced mammary gland carcinoma in albino wistar rats. Animals were randomized into four groups (six animals in each). Group I (sham control 0.9 % normal saline p.o.); Group II (toxic control, MNU 47 mg/kg, i.v.); Group III (α-chymotrypsin, 5 mg/kg, p.o.); Group IV (α-chymotrypsin, 10 mg/kg p.o.). Toxicity was induced by single i.v. injection of MNU followed by α-chymotrypsin supplementation therapy for 100 days. MNU treatment was evident with increased alveolar bud count, differentiation score, upregulated inflammatory enzymes markers (COX, LOX and NO) antioxidative stress markers (TBARs, SOD, catalase and GSH).MNU associated toxicity was also ascertained by PGP 9.5 and NF-κB expression in the mammary gland tissue followed by FAME analysis for fatty acid profiling. α-chymotrypsin afforded significant protection against the deleterious effects of MNU.

Venous leg ulcer slough is unpleasant to the patient and difficult to manage clinically. It harbours infection, also preventing wound management materials and dressings from supporting the underlying viable tissues. In other words, slough has significant nuisance value in the tissue viability clinic. In this study, we have sought to increase our knowledge of slough by building upon a previous but limited analysis of this necrotic tissue. In particular, slough has been probed using Western blotting for the presence of proteins with the capacity to engage microbial surface components recognising adhesive matrix macromolecules. Although the samples were difficult to resolve, we detected fibrinogen, fibronectin, IgG, collagen, human serum albumin and matrix metalloproteinase-9. Furthermore, the effect of a maggot-derived debridement enzyme, chymotrypsin 1 on macromolecules in slough was confirmed across seven patient samples. The effect of chymotrypsin 1 on slough confirms our thesis that this potential debridement enzyme could be effective in removing slough along with its associated bacteria, given its observed resistance to intrinsic gelatinase activity. In summary, we believe that the data provide scientists and clinicians with further insights into the potential molecular interactions between bacteria, wound tissue and Lucilia sericata in a clinically problematic yet scientifically interesting wound ecosystem., (© 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Objective: Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Very little is known about the causes of AD, except that its end stages involve extensive neuronal loss and the appearance of distinctive neuropathological features. This study was under taken to investigate the role of α-chymotrypcin (α-ch) in management of AD-induced in ovariectomized rats., Design: Sixty female Sprague Dawley rats were divided into four groups n=15, (1) normal control group (con), (2) group underwent surgery to remove ovaries (ovx control group), (3) ovx group received aluminum chloride in a dose of 17 mg/kg daily for 2 months to induce AD (AD group), (4) AD group treated with α-chymotrypcin (α-ch) at dose (8.1 unit/rat/day) which is equivalent to the recommended human dose (α-ch-treated group) for three months. At the end of the experimental period, rats were sacrificed; brain samples were obtained for different biochemical analyses and histopathological examination. The biochemical analyses included determination of tumor necrosis factor-α (TNF- α), IL-18, monocyte chemo attractant protein-1 MCP-1, FAS, B-cell lymphoma 2 (Bcl2)., Results: In comparison with normal control group, the ovx control group recorded significant increase in the brain levels of TNF-α, IL-18, MCP-1 and FAS. On the other hand, the brain level of Bcl2 was significantly decreased. Also, AD group showed a significant increase in TNF-α, IL-18, MCP-1 and FAS levels in brain tissue. In contrast, significant decrease in brain Bcl2 level was detected in AD group as compared to the ovx control group. However, the treatment of AD group with α-chymotrypcin caused an improvement in the most studied biochemical parameters as indicated by decreased brain levels of TNF-α, IL-18, MCP-1 and FAS accompanied with significant increase in the level of Bcl2 compared to AD group. Histopathological investigation of brain tissue of ovx rats administered with aluminum (AD group) showed AD plaques. While, AD group treated with α-chymotrypcin showed great improvement in the brain morphological structure with the disappearance of amyloid plaques., Conclusion: This study revealed that α-chymotrypcin significantly ameliorates the neuroinflammation characterizing Alzheimer's disease in ovariectomized rats due to it's proteolytic activity as well as it's anti-inflammatory effect., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

Larval biotherapy is a debridement tool used in wound management. The mechanism of action involves degradation of eschar by serine proteases including chymotrypsin within the alimentary fluids of first instar Lucilia sericata. With the rationale of obviating some limitations of biotherapy, including cost, complexity of use, and patient reticence, the present study describes a mobile hydrogel formulation containing freeze-dried recombinant L. sericata chymotrypsin designed for topical application. Neither freeze-drying nor formulation into the hydrogel significantly attenuated the measured activity of released enzyme compared to fresh-frozen enzyme in aqueous solution. Gel electrophoresis confirmed qualitatively that the chymotrypsin/hydrogel formulation both with and without supplementary urea at 10% (w) /(v) degraded human chronic wound eschar ex vivo. Mindful that the hallmark of intractability of chronic wounds is aberrant biochemistry, the pH activity profile for the enzyme/hydrogel formulation was compared with exudate pH in chronic wounds of mixed aetiology in a cohort of 48 hospital in-patients. Five patients' wounds were acidic, however, the remainder were predominantly alkaline and coincided with the pH optimum for the insect enzyme. Thus, a recombinant L. sericata chymotrypsin and hydrogel formulation could represent a pragmatic alternative to larval therapy for the management of chronic wounds., (Copyright © 2011 American Institute of Chemical Engineers (AIChE).)

Cheilitis granulomatosa is a rare disease characterised by the recurrent labial swelling of one or both lips with the possibility of the condition to remain on a permanent basis. The disease may appear independently or it may be linked to a paralysis such as the facial and lingua plicata which then characteristic of the Melcersson-Rosenthal Syndrome. The aim of this paper is to show a case of a patient with the granulomatosae cheilitis and lingua plicata whose reaction to the Chymoral Forte treatment was excellent.

Aim: To evaluate changes on venous diameter and perimeter of lower limbs in chronic venous disorder (CVD) patients after different clinical treatments for four weeks., Methods: Fifty-two female patients classified as C2,s or C2,3,s (CEAP classification) were allocated consecutively in three groups: Cirkan (40 mg of the root extract of Ruscus aculeatus + 100 mg of flavonoid hesperidine methylchalcone + 200 mg of vitamin C per pill); elastic compression stockings (ECS) and no treatment (NT). Diameters were determined by duplex ultrasound and perimeter with Leg-O-Meter., Results: After treatment, Cirkan significantly decreased popliteal vein and great saphenous vein (GSV) diameters bilaterally and ECS decreased popliteal vein diameter bilaterally and GSV and varices only on the left limb. Perimeters changed only with ECS. Clinical scores changed between Cirkan x NT and ECS x Cirkan. Disability score varied for ECS x NT and Cirkan x NT. chi2 test detected different distribution frequency for C3 and C2 classes according to treatment: ECS (both limbs) and Cirkan (only left limb). Varices and anatomical scores did not change., Conclusions: ECS emerges as the most effective clinical treatment tested but improvements with Cirkan on vein diameter and CEAP class were also observed. Clinical scores improved due to pain relief and edema reduction (ECS). These findings point to a positive effect of Cirkan, suggesting that venotonic drugs should be taken into account in the treatment of CVD.

In the early 20th century, advocacy of the enzyme therapy of cancer was primarily the work of one man, John Beard, DSc (1858-1924). He and his collaborators made a determined effort to establish this mode of therapy, especially in the years 1905 to 1911. Despite a brief flowering of international interest, Beard's efforts came to naught. During the 20th century, there was a succession of American researchers who continued to investigate this topic. This included Marshall William McDuffie, MD (1882-1945), Frank LeForest Morse, MD (1876-1953), Franklin Lloyd Shively, MD (1887-1971), and William Donald Kelley (1926-2005). In central Europe, India, and other parts of the globe, the use of pancreatic enzymes as an adjuvant treatment for cancer has become a fairly routine practice, at least among those doctors who utilize complementary and alternative medicine (CAM). It is also a well-established method for reducing inflammation and mitigating the adverse effects of cytotoxic treatment.

Objectives: To evaluate changes on cutaneous microangiopathy in chronic venous disorder (CVD) after use of Cirkan [venotonic drug containing Ruscus aculeatus (plant extract), hesperidine methylchalcone (flavonoid) and vitamin C], elastic compression stockings (ECS) or no treatment for four weeks., Patients and Methods: Fifty-five female patients (85 legs), 25 to 57 years, with at least one limb classified as C2,s or C2,3,s (CEAP classification), were allocated consecutively, according to entrance order, in these three groups. Ten healthy women age-matched were also investigated. Using orthogonal polarization spectral technique (noninvasive method), measurements of functional capillary density (FCD, number of capillaries with flowing red blood cells/mm(2)), capillary morphology (CM, % of abnormal capillaries/mm(2)) and diameters (mum) of dermal papilla (DDP), capillary bulk (DCB) and capillary limb (CD) were obtained on the medial perimalleolar region and later analyzed using CapImage software., Results and Conclusions: CVD patients showed significant changes on CD and CM compared to healthy subjects in agreement with our previous findings (J Vasc Surg 43:1037-1044, 2006). On Cirkan-treated patients, after 4 weeks, CD decreased on both limbs and CM improved on the left one, suggesting an amelioration of the chronic venous hypertension. No significant changes could be detected on other patient groups. These results confirm the existence of microcirculatory dysfunction in early stages of CVD, probably due to post-capillary hypertension, and further support the venotonic action of Cirkan.

Purpose: To investigate the efficacy and safety of Wobe-Mugos E (proteolytic enzymes) for amelioration of early side effects of radiotherapy for head-and-neck tumors, particularly oral mucositis., Patients and Methods: The study was a prospective, randomized, multicenter, placebo-controlled, triple-blind phase III study with parallel groups. 69 patients with carcinomas of the oropharynx or the oral cavity were enrolled between 1996 and 2000 in five centers; 54 of these were recruited in Dresden. Of the 69 patients, 61 (Dresden: 46) were available for analysis. The proteolytic enzymes tested (Wobe-Mugos E) comprised papain 100 mg, trypsin 40 mg, and chymotrypsin 40 mg., Results: Wobe-Mugos E was well tolerated. For the maximum mucositis scores, no statistically significant differences were found between the placebo and the verum group. The average mucositis score over weeks 1-6 revealed a significant difference in favor of the placebo arm, based on an earlier onset of mucositis in the Wobe-Mugos E group., Conclusion: The present study failed to demonstrate any effect of treatment with Wobe-Mugos E on radiotherapy side effects in patients treated for head-and-neck tumors. In particular, there was no beneficial effect on radiation-induced early oral mucositis.

Background: Lung cancer is the most common cancer in the world accounting for 17.6% cancers worldwide. The AAR i n I ndian population varies f r om 0.98-15.55. The aim of t he present study was to analyze areduction in neoadjuvant chemotherapy related acute toxicity in locally advanced lung cancer (stage IIIA and III B) using Wobe Mugos E and its evaluation using micronuclei as a cytogenetic marker. Micronuclei, which are cytoplasmic fragments of DNA, have been used as a biological dosimeter to assess DNA damage., Material and Methods: Fourty patients of locally advanced NSCLC were randomized into two study groups between 2001-2003. One group received neoadjuvant chemotherapy using Cisplatin and Etoposide. The other group received neoadjuvant chemotherapy using Cisplatin and Etoposide along with Wobe Mugos E which is a proteolytic enzyme preparation. A study of micronuclei frequency was done pre and post chemotherapy in both groups., Results: Thirty eight patients were available for final evaluation. Anemia was the most common hematological toxicity observed. Nausea and vomiting were the most common non -hematological toxicity seen. Wobe Mugos E was found to reduce the incidence of leucopenia (p = 0.005), nausea (p=0.004), vomiting (p= 0.003), sensory neuropathy (p = 0.032) and treatment related depression (p= 0.005). A reduction in micronuclei was seen in patients in patients on Wobe Mugos E. (p =0.01)., Conclusion: Neo-adjuvant chemotherapy related acute toxicity is a major problem in patients with advanced lung cancer. A reduction in micronuclei frequency shows Wobe Mugos E to be effective in reducing chemotherapy related acute toxicity.

Background: While treating acutely inflammed piles, surgeons in general prefer to stick to the conservative method of treatment. This includes bed rest in a Trendelenburg's or jack-knife position, administration of liquid diet, stool softeners, antibiotics, and anti-inflammatory drugs along with warm Sitz baths and local application of glycerin and magnesium sulphate paste. We introduced an additional method in treating acutely inflammed piles. Ten tablets of trypsin and chymotrypsin (Chymoral forte, Elder Pharmaceuticals India) were powdered and were mixed with 30 grams of heparin (Thrombophobe, German Remedies Ltd, Germany) ointment. This paste was applied to the inflammed pile mass. In all, 67 received this in patient treatment with an average hospital stay of 2 days. The results were compared using chi2 test with similarly placed 22 patients who were treated with the conventional method only., Results: In the patients receiving the application of the enzyme paste, local pain was reduced to a great extent, the defecation was comfortable, there was negligible local pruritus, and the routine body movements of the patient were painless. Local signs observed in the form of the size of the piles, perianal edema, and tenderness, were also found to be significantly reduced., Conclusion: The results of this study demonstrate that the additional use of a heparin-enzyme paste applied directly over the pile masses significantly improves the healing and resolution of acutely inflammed hemorrhoids. The effectiveness of the traditional conservative method of treatment could be gainfully supplemented by use of the pharmaceutical preparation suggested in this study.

The present study was carried out in burn patients administered with Trypsin-Chymotrypsin (Chymoral Forte D.S.) preparation to observe if the acute-phase protein levels in the serum are modulated through the synthesis of IL-1beta and IL-6 and if the severity of the inflammatory phase could be regulated. The effects of Trypsin-Chymotrypsin preparation on the modulation of cytokine levels particularly, IL-6 and IL-1beta were analyzed in serum samples of 15 burn patients and compared with untreated controls. Significant differences in cytokine levels (P<0.05) were observed in untreated burn patients and Trypsin-Chymotrypsin preparation treated patients. There were significant variations in serum IL-6 and IL-1beta on the day of admission and post burn day 10 in treated as well as untreated burn patients. Patients with a higher percentage of total body surface area and sepsis showed a significant increase in IL-1beta and IL-6 in the serum. An increase in serum levels of both cytokines was observed on post burn day 1 and a significant decrease was observed in Trypsin-Chymotrypsin preparation treated patients on days 7 and 10. The possible role of the inflammatory cytokines in the pathophysiology of burns is discussed.

The efficacy of prostatic drainage using transurethral vacuum aspiration (Introl-4 unit) and transrectal pneumovibromassage (PVM-R-01) was compared in 1511 patients with chronic obstructive prostatitis. The drainage was accompanied by local (urethral, rectal and urethral-rectal tripsin or chimotripsin electrophoresis) or systemic enzymic therapy (vobenzim). The highest effect of the drainage was achieved in patients pretreated for 5-7 days with systemic enzymes. Transrectal pneumovibromassage proved more effective and safe but the transurethral technique if indicated can be also used in the combined treatment.

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.

Purpose: Based on in vitro and on clinical evidence of protection against acute side effects of radiation, a prospective randomized, open study was performed to determine the efficacy of an oral proteolytic enzyme preparation in patients with head and neck cancer receiving conventional fractionated radiation therapy., Methods: Patients with stage T3/T4 head and neck cancer were eligible. One hundred patients from two centres were entered into the study. 60Co gamma-radiation was delivered at a standard daily radiation dose of 2 Gy in 25-35 fractions over a period of 6-7 weeks. Two lateral parallel opposing fields were used with a portal area of 10 x 15 cm. Patients assigned to the test group arm additionally received enzyme tablets orally t.i.d. starting 3 days prior to radiation therapy, and continuing up to 5 days after completion of the course of radiation therapy. Patients in the control arm were not given any drug or placebo. Acute radiation side effects were described as mucositis, skin reaction, dysphagia, and were graded at each visit during and after radiation therapy, following RTOG/EORTC criteria., Results: The severity (maximum extent) of acute radiation therapy side effects was significantly less in enzyme-treated patients than in control patients: mucositis (mean: 1.3 vs 2.2, P < 0.001), skin reaction (1.2 vs 2.4, P < 0.001) and dysphagia (1.4 vs 2.2, P < 0.001). The duration of these side effects as well as the sum scores of side effects were also less in the study arm., Conclusions: Combination of enzyme therapy with conventional fractionated radiation therapy was feasible and well-tolerated. There was significant protection against acute side effects of radiation therapy in the study arm. Not only was the severity of acute side effects less but the duration was shorter and the time to onset was also delayed. Prospective randomized double-blind studies would verify this role of an oral enzyme therapy as standard co-medication with radiation therapy to the head and neck region.

Purpose: [corrected] To evaluate the impact of postoperative treatment with an oral enzyme (OE) preparation given complementary to an antineoplastic therapy in patients with breast cancer., Methods: The design of this epidemiological study was a retrolective cohort analysis with parallel groups. Design and conduct of the study were performed to current standards for prospective, controlled clinical trials. A cohort of 2,339 breast cancer patients undergoing surgical intervention and radio-, chemo- or hormonal therapy were studied in 216 centres. Of the 2,339 patients, 1,283 received complementary treatment with OE and 1,056 did not receive OE. Patients with other complementary medications were excluded and the final analysis was performed with the data from 649 patients, of whom 239 (37%) were additionally treated with OE (test group) and 410 (63%) without OE (control group). The median follow-up time for the test group was 485 days and for the control group 213 days. The primary endpoint of the study was to determine whether complementary treatment with OE can reduce typical disease- or therapy-associated signs and symptoms (gastrointestinal symptoms, mental symptoms, dyspnoea, headache, tumour pain, cachexia, skin disorders, infections, and side effects associated with the antineoplastic therapy) in patients with breast cancer. Imbalances for causal effects (covariates) were adjusted for by means of the propensity score. Outcome analysis was performed by estimating the linear regression between change in symptom score and propensity score with all data and using this regression line to calculate the change in symptom score which would be expected for each patient. Tumour-associated events (recurrence, metastasis, and death) were evaluated in terms of the number of events observed and time to event. The safety of treatment with OE was analysed in terms of the number and severity of adverse events, their duration, treatment and outcome., Results: For all symptoms except tumour pain, the adjusted mean improvement in symptom scores was larger in the test group than in the control group. The adjusted difference was statistically significant for all symptoms, except tumour pain and infections. The results show that the typical disease- and therapy-associated signs and symptoms in patients on complementary therapy with OE during postoperative treatment were significantly less. For 75% of the test group and 55% of the control group the physician recorded "no signs and symptoms". A clear reduction in the side effects of radiotherapy and chemotherapy was documented in 74% of the test group and 55% of the control group. Analysis of survival, recurrence, and metastasis demonstrated a reduced number of events in the test group. There was evidence of a beneficial influence of OE on time to event, although the median observation time was too short in these breast cancer patients to draw definite conclusions. The safety component was judged in 98% of the test group and 76% of the control group as "very good" or "good". In the total sample of 2,339 patients, the rate of OE-associated adverse reactions was 3.2%. All side effects were mild to moderate gastrointestinal symptoms., Conclusion: Complementary treatment of breast cancer patients with OE improves the quality of life by reducing signs and symptoms of the disease and the side effects of adjuvant antineoplastic therapies. This epidemiological retrolective cohort analysis provides evidence that the patients may also gain benefit by a prolongation of the time to event for cancer recurrence, metastasis and survival. OE was generally well tolerated.

Purpose: To evaluate the impact of postoperative treatment with an oral enzyme (OE) preparation given complementary to an antineoplastic therapy in patients with all stages of colorectal cancer., Methods: The design of this epidemiological study was a retrolective cohort analysis with parallel groups. Design and conduct of the study were performed to current standards for prospective, controlled clinical trials. Of a cohort of 1,242 patients with colorectal cancer (documented in 213 centres), 616 had received complementary treatment with OE (182 OE only, 405 other complementary drugs, 29 protocol violators) and 626 had not received OE (368 control only, 229 other complementary drugs, 29 protocol violators). Of 1,162 patients who had undergone primary surgery, 526 received adjuvant chemotherapy and 218 radiotherapy. The median follow-up time for the OE group was 9.2 months and for the control group 6.1 months. The primary test criterion of efficacy for OE treatment was the multivariate effect size of the changes from baseline of the disease- and therapy-associated signs and symptoms (nausea, vomiting, changes in appetite, stomach pain or stomach disorder, tiredness, depression, memory or concentration disorder, sleep disturbance, dizziness, irritability, dyspnoea at rest, dyspnoea during activity, headache, tumour pain, cachexia, skin disorders and infections). Tumour-related events, e.g. death, were evaluated by the number of events observed and time to event. Safety of treatment with OE was analysed in terms of number and severity of adverse events, their duration, treatment and outcome., Results: A significant reduction in disease-associated signs and symptoms was observed in patients treated with OE alone, but not in those receiving OE in addition to other complementary treatments. Adverse reactions to chemo- and radiotherapy were diminished in all patients receiving OE. Analysis of survival did not demonstrate a reduced number of deaths in the OE group. However, a trend to prolongation of survival was demonstrated, particularly in the patients with disease stage Dukes' D, in the subgroup receiving OE in addition to other complementary treatments. Similar but less-pronounced trends were observed for disease stages Dukes' B and C. In the OE group, 21 of 616 patients (3.4%) experienced OE-associated adverse reactions, all of them mild to moderate gastrointestinal symptoms., Conclusion: Complementary treatment of colorectal cancer patients with OE improves their quality of life by reducing both the signs and symptoms of the disease and the adverse reactions associated with adjuvant antineoplastic therapies. This epidemiological retrolective cohort analysis provides evidence that patients may also benefit by a prolongation of survival time. OE were generally well tolerated.

Purpose: The use of additional therapy with an oral enzyme preparation containing trypsin, chymotrypsin and papain has been suggested for the reduction of toxicity due to radiation therapy. This study was conducted to test the efficacy and tolerability of this enzyme combination in preventing or reducing the acute side effects of radiation therapy in patients with locally advanced cervical cancer., Methods: A prospective, randomised, open, clinical trial was carried out on 120 patients (aged 24-85 years) with locally advanced, biopsy-proven carcinomas of the uterine cervix (stages IIa, lIb or IIIb). Patients received 50 Gy of external radiation therapy over a period of 5 weeks, followed by intracavitary brachytherapy (20-30 Gy). Patients assigned to the test group (60 patients) received additional treatment with enzymes. Patients were evaluated at weekly intervals for acute radiation therapy-related side effects, according to the RTOG/EORTC grading criteria, and then after the end of radiation therapy for another 8 weeks. Occurrence of adverse events, if any, was also recorded., Results: The study revealed that the maximum extent of acute radiation side effects was reduced in the enzyme group: skin reactions (mean: 0.97 vs 1.68 in the control group, P < 0.001), vaginal mucosal reactions (0.55 vs 0.85, P = 0.10), genitourinary symptoms (0.93 vs 1.38, P < 0.001) and gastrointestinal reactions (1.12 vs 1.30, P = 0.12). The sum-scores during treatment, expressed as area under the curve, were significantly less in the enzyme treated patients. In the follow-up visits all observed side effects of radiation therapy were of lower intensity in the enzyme group than in the control group., Conclusions: In patients with locally advanced cancer of the uterine cervix, oral enzyme therapy was found to be effective in significantly reducing radiation therapy-related side effects such as genitourinary symptoms, subcutaneous changes and reactions of the vaginal mucosa.

Examined in treating rats with Guerin's carcinoma with doxorubicin was the possibility that the polyenzymic drug preparation wobe-mugos E had hepatoprotective, cardioprotective and myeloprotective effects. In intramuscular administration wobe-mugos E has not been found to stimulate the tumour growth, it exhibited a manifest hepatoprotective and myeloprotective actions with respect to adverse reactions of doxorubicin but failed to diminish cardiotoxicity of the latter. The protective effect of the above polyenzymic drug was of a dose-dependent character.

Set out in the paper are results of treatment of those patients with carcinoma of the lung, uterine cervix, hysterocarcinoma, breast cancer, malignant thymomas, malignant non-Hodgkin's lymphomas, and lymphogranulematosis having been administered combined, chemoradiation or radiation treatments against the background of a complex of accompanying therapy involving systemic enzymotherapy. Polyenzymic drugs were found to be capable of improving results of treatment of acute radiation reactions and preventing postradiation fibrous changes in the lungs, skin, fatty tissue, soft tissue, liver, kidneys. Thus, systemic enzymotherapy is capable of improving the quality of life and results of treatment of oncological patients.

The protective effect of Wobe-Mugos appliance on the kidney function and biochemical state in polyuric stage of sublimate nephropathia at the moment of tubulointerstitial component formation was revealed in experiments on 40 white male rats. It appeared in the increase of hydrogenous ion excretion, titred acids, renal tissue fibrinolytic and proteolytic activity. The succinatdehydrogenase activation in renal cortex matter pointed out on the improvement of energy balance.

This study was mainly aimed to investigate the efficacy of trypsin:chymotrypsin to elicit anti-oxidant properties. In our earlier studies it was observed that the enzyme preparation exhibited an anti-inflammatory action as there was a remarkable reduction in oedema formation and tissue destruction. This led to further study on the amount of lipid peroxidation products formed and the levels of enzymatic and non-enzymatic anti-oxidants and relative trace element contents of copper, selenium, iron and zinc during administration of the enzyme preparation. Decreased formation of lipid peroxidation products was observed in treated group in comparison with the untreated group. Higher levels of enzymatic anti-oxidants mainly super oxide dismutase, catalase, glutathione peroxidase and glutathione-s-transferase and non-enzymatic antioxidant namely ceruloplasmin persisted for a longer period of time in the treated group than in the untreated group. No statistical significance was observed in non-enzymatic antioxidants viz. ascorbic acid and tocopherol levels in both the groups. Increased serum copper and selenium levels in the treated group could be related to higher levels of the ceruloplasmin and glutathione peroxidase observed in the treated group. The above studies support the finding that treatment with the enzyme preparation reduced tissue destruction leading to decreased formation of free radicals and subsequent effective scavenging of free radicals by the higher levels of enzymatic and non-enzymatic anti-oxidants.

We describe the clinical history, histopathology and treatment of a two and a half year old boy. He presents with a chronic, unilateral and (pseudo) membranous conjunctivitis, preceded by ear-nose-throat problems and arthritis. The case was considered to be a ligneous conjunctivitis. Treatment consisted of repeated removal of the membranes, combined with topical hyaluronidase, alpha-chymotrypsin, cyclosporin, heparin and antibiotics, and was deceiving.

The clinical, histopathologic features, and treatment outcomes in 3 patients with ligneous conjunctivitis are described. Bilateral, idiopathic membranes occurred in the palpebral conjunctiva in 2 patients. In 1 patient, unilateral conjunctival changes occurred in the bulbar conjunctiva, at the site of pterygium excision. Treatment included topical hyaluronidase, chymotrypsin, heparin, and cyclosporine and surgical excision with limited or no success. In one patient, conjunctival autografting from the normal fellow eye resulted in pseudomembrane formation at the donor site in the previously unaffected eye. Histopathological evaluation of excised membranes revealed the presence of amorphous eosinophilic hyaline material and chronic inflammatory cells. Immunohistochemical study revealed a predominance of T-lymphocytes. This case series confirms the recalcitrant clinical course of ligneous conjunctivitis. Conventional treatment modalities described in literature were not useful in the management of this condition. Surgical manipulation of the unaffected fellow eye in patients with unilateral disease can result in pathologic conjunctival changes, and is best avoided.

The levels of marker enzymes for liver function, namely transaminases (SGPT, SGOT), creatine phosphokinase (CPK), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were estimated in the sera of burn patients by administering trypsin: chymotrypsin preparation and comparing with an untreated group. Neutrophil proteolytic activity was also measured by assaying the lysosomal enzymes, namely neutrophil elastase and cathepsin D. Our earlier studies have already proved the efficacy of the above enzyme preparation to burn patients on the enhancement of vascular responses during the acute phase of the burn injury. These beneficial responses were brought about by the modulation of acute phase proteins expressed in the liver. Hence, it is of interest to study the changes in the above mentioned liver enzymes and certain lysosomal enzymes in the serum during the first 10 days of burn injury. The levels of liver and lysosomal enzymes markedly decreased in the treated group when compared with the untreated group. The enzyme studies clearly indicated that the initial rise in the liver enzymes was minimized in the treated group when compared with the untreated group and this helped in reducing the stress to the liver in the treated cases. The increase in the activity of alpha 1-antitrypsin and alpha 2-macroglobulin and decreased levels of C-reactive protein are attributed to the reduction of proteolytic enzyme levels in the treated group and minimizing the degradative changes during wound repair.

A study was carried out to investigate the efficacy of trypsin: chymotrypsin (Chymoral forte DS) preparation on burn patients by analysing the changes taking place in serum acute-phase proteins. Serum proteins were analysed qualitatively and quantitatively for both control and enzyme-treated groups by the methods of Western Blot, ELISA and Turbidimetric assays. Furthermore, the trypsin inhibitory capacity (TIC) of the sera was also determined. Significant differences were observed between a control group of patients and a parallel group treated with trypsin: chymotrypsin preparation. During the first phase of burn wounds an initial rise was seen in C-reactive protein, alpha 1-antitrypsin, alpha 2-macroglobulin and TIC in both the groups. In the following days, enzyme preparation inhibited the rise in C-reactive protein titres and enhanced the rise in alpha 1-antitrypsin, alpha 2-macroglobulin and TIC. The above studies clearly indicate that the changes in serum acute-phase proteins between the control and treated groups reflect the anti-inflammatory activity and hence the therapeutic efficacy of Chymoral forte DS.

A comparative study was performed of the caseinolytic, necrolytic and fibrinolytic activities of a crab collagenase product prepared from the hepatopancreas of the king crab (Paralithodes camtschatica) and four enzyme preparations (trypsin/chymotrypsin and protease complexes isolated from Aspergillus terricola, Carica papaya and pseudomonodaceae). This paper reports an in vitro investigation, an in vivo study with rats and a clinical evaluation. It was found that crab collagenase has the highest proteolytic activity measured with respect to fibrin clot and necrotic eschar in vitro although its caseinolytic activity is the lowest. A clinical trial involving 21 patients with leg ulcers confirmed the clinical efficiency of crab collagenase compared with trypsin/ chymotrypsin. The results suggest that crab collagenase is useful in wound debridement.

A new wound cleansing agent consisting of bead cellulose with covalently, firmly bound proteolytic enzyme, chymotrypsin, was prepared. It was found that this preparation can be applied in the treatment of suppurating wounds of all types with very good results.

Background: Ligneous conjunctivitis is a rare acute or subacute membranous conjunctivitis of unknown etiology for which no generally accepted form of treatment is available., Methods: Between 1972 and 1993, 17 patients with ligneous conjunctivitis were treated with excision biopsy, meticulous hemostasis, and immediate, intensive topical treatment with heparin, steroids, and, in 12 patients, alpha-chymotrypsin until all signs of conjunctival inflammation had subsided., Results: On histologic examination, the lesions consisted of subepithelial deposits of fibrin in all patients. Eight patients had no recurrence (mean follow-up, 33.1 months) and in four patients the conjunctivitis was controlled after one repeat excision and topical treatment (mean follow-up, 40.3 months). One patient had three recurrences before responding to treatment (follow-up, 24 months). In four patients, treatment was unsuccessful, although lesion-free intervals were longer than usually seen in this condition (mean, 7.8 months)., Conclusion: These results suggest that intensive and early use of topical heparin may improve therapy results in ligneous conjunctivitis.

50 patients with fallopian tube obstruction were initially treated by catheter recanalization, and then randomly divided into two groups. Chinese medicine group (CMG) treated with Tongjingbao and Angelicae Complex Injection and Western medicine (Gentamycin, Dexamethasone, Chymotrypsin) group (WMG) as a control. The course of treatment was three months. Before and after treatment, the hemorheology change was analysed. After treatment, all patients except subsequent pregnancy were repeatedly performing hysterosalpingography. The results showed effective rate of recanalization was 94%; corrected pregnancy rate was 100% in CMG and 50% in WMG; the reocclusion rate of fallopian tube was 9% in CMG and 25% in WMG (P < 0.05). The difference of hemorheology change between two groups was significant (P < 0.01) and it was also different before and after treatment in CMG (P < 0.01). This study showed that catheter recanalization was effective in recanalizing the mechanical occluded fallopian tube. The Chinese medicine would inhibit the reocclusion and re-adhesion of tube.

Twenty patients with Guinea worm disease having a total of 29 emerging worms in a rural village of North West Frontier Province, were put on a 5-day course of antibiotics and antiinflammatory drugs and compared with age-matched control patients. The ulcer sites of emerging worms were kept continuously moist, and 18 worms were extracted from 14 patients during the above mentioned period. The average time taken for the entire worm to be expelled in these patients was considerably shorter (13.6 days) than in controls (89 days). Seven (39%) of these worms were expelled spontaneously whereas the remaining 11 (61%) were pulled out manually with relative ease. Fifteen (75%) patients in this study had a single emerging worm, three (15%) had two emerging worms and two (10%) patients had four or more emerging worms.

Catheter-related infections pose a hazard to both humans and laboratory animals. The aim of this study was to develop a technique preventing bacterial colonization of intravascular catheters. In 27 dogs a total of 70 catheters were implanted. On an average catheters were used for 207 days. Three protocols were compared: (1) flushing the catheters with a heparinized solution; (2) filling only the catheter lumen with alpha-chymotrypsin solution (225 units/ml); (3) filling only the catheter lumen with a solution containing a mixture of the aminoglycoside antibiotic gentamicin (20 mg/ml) and chymotrypsin (225 units/ml). Catheter fillings were always withdrawn before catheter use. Catheter exit sites were all treated with povidone iodine ointment once a day. Body temperatures and weights were recorded, bacteriological and electron microscopical examinations of catheters performed. Without gentamicin filling all catheters were colonized after a few weeks. The dogs showed clinical signs of chronic bacteraemia. Gentamicin filling eradicated colonization. No further bacteraemia was observed. We conclude that filling only the catheter lumen with a concentrated solution of chymotrypsin and gentamicin, combined with measures to prevent infections via the subcutaneous catheter tunnel, is an effective and safe technique to prevent catheter-related infections.

Eight-cell, zona pellucida-intact mouse embryos were exposed to the following substances or procedures that have been reported to have germicidal effects to determine if the embryos would survive and develop under in vitro conditions: the photosensitive substances hematoporphyrin, hematoporphyrin derivative, 8-methoxypsoralen, 4,5',8-trimethylpsoralen, and thiopyronine; the enzymes lipase (0.5%), phospholipase C (2 U/ml), chymotrypsin (0.5%), and trypsin (0.5%); pH 5.0; and helium/neon laser light, visible light, ultraviolet A light, and ultraviolet C light. Under the conditions used, embryos were not adversely affected by hematoporphyrin and/or helium/neon laser light; methoxypsoralen and/or ultraviolet A light; lipase; trypsin; pH 5.0 for 20 min; and visible light. Variable results were obtained from hematoporphyrin derivative with laser light. Thiopyronine, trimethylpsoralen in combination with ultraviolet A light, and ultraviolet C light killed embryos, and chymotrypsin and phospholipase C were harmful at 10- and 15-min exposure times, respectively.

The present study reveals our experience in the medical management of 30 cases of progressive/malignant exophthalmos, employing costicosteroid, b-blocker, diuretic and a preparation containing proteolytic enzymes. There was encouraging improvement in terms of symptoms, proptosis and optic nerve compression, while reduction of ophthalmoplegia was not so satisfactory. However, none of the patients needed decompression surgery.

Clinical, serologic, and immunologic studies carried out before and after treatment in 102 patients treated with benzylpenicillin according to the scheme developed at the Kuibyshev Medical Institute and chymotrypsin and in 55 patients treated with penicillin alone evidence the efficacy of chymotrypsin. The drug favorably influenced the terms of syphilid regress, negative answers were sooner obtained in classical serologic tests, and the time course of cellular immunologic tests was more favorable.

The study has involved 3702 male patients with gonorrhea. Of these 62 percent were fresh cases, 38 percent chronic ones; there were 218 patients (5.9 percent) with recurrences, of these 63.3 percent with new relapses and 36.7 percent with chronic ones. 85.3 percent of patients developed monorelapses. The recurrences were equally frequent after antibiotic therapy (50.2 percent) and after combined treatment (49.8 percent). Proteolytic enzymes (chymotrypsin, trapsin 5 mg twice daily with a 12 hrs interval) in combination with an antibiotic were administered to 242 patients with gonorrhea complicated by epididymo-orchitis and with gonorrhea relapses. Etiologic cure was achieved in all of them; postgonorrheal conditions were recorded in 6-7 percent and depended on the antibiotic administered; in reference patients recurrences were recorded in 4.2-6.5 percent of cases, postgonorrheal conditions in 14-21.4 percent of cases. Enzymic therapy helped reduce the length of inpatient therapy of a patient by 5.93 days on an average in cases with orchidoepididymitis and by 14.64 days in gonorrhea relapses, with the economic effect per worker being 131.4 and 307.2 rubles, respectively.