Trypsin Pre-Treatment Combined With Growth Factor Functionalized Self-Assembling Peptide Hydrogel Improves Cartilage Repair in Rabbit Model.

The objective of this study was to improve cartilage repair and integration using self-assembling KLD hydrogel functionalized with platelet-derived growth factor-BB and heparin-binding insulin-like growth factor-1 with associated enzymatic trypsin pre-treatment of the native cartilage. Bilateral osteochondral defects were created at the central portion of the femoral trochlear groove of 48 skeletally mature, white New Zealand rabbits. One limb received a randomly assigned treatment and the contralateral limb served as the control. Treated defects were exposed to trypsin for 2 min and filled with self-assembling KLD hydrogel only, or associated to growth factors. All control limbs received KLD hydrogel alone or received only trypsin but not hydrogel. Ninety days post-defect creation, the rabbits were euthanized and magnetic resonance imaging, radiography, macroscopic evaluation, histology, and immunohistochemistry of the joint and repaired tissue were performed. Mixed model analyses of variance were utilized to assess the outcome parameters and individual comparisons were performed using Least Square Means procedure and differences with p-value < 0.05 were considered significant. Trypsin enzymatic pre-treatment improved cellular morphology, cluster formation and subchondral bone reconstitution. Platelet-derived growth factor-BB improved subchondral bone healing and basal integration. Heparin-binding insulin-like growth factor-1 associated with platelet-derived growth factor improved tissue and cell morphology. The authors conclude that self-assembling KLD hydrogel functionalized with platelet-derived growth factor and heparin-binding insulin-like growth factor-1 with associated enzymatic pre-treatment of the native cartilage with trypsin resulted in an improvement on the cartilage repair process. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2307-2315, 2019.

A Randomized, Clinical Trial to Evaluate Efficacy and Tolerability of Trypsin:Chymotrypsin as Compared to Serratiopeptidase and Trypsin:Bromelain:Rutoside in Wound Management.

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).

Rutoside and Hydrolytic Enzymes Do Not Attenuate Marathon-Induced Inflammation.

INTRODUCTION: Vigorous and prolonged exercise such as marathon running increases inflammatory markers and the risk of upper respiratory illness (URI) in athletes. Nutritional supplements are being tested as countermeasures of exercise-induced inflammation and immune dysfunction. METHODS: In this prospective randomized, double-blind, placebo-controlled phase I trial, healthy male runners (N = 138, age 42 ± 11 yr) were supplemented with rutoside (600-1200 mg·d) and hydrolytic enzymes (540-1080 mg·d bromelain, 288-576 mg·d trypsin) (WOB) or placebo (PL) for 1 wk before and 2 wk after the Munich Marathon 2013. Blood samples were collected 5 wk prerace and immediately, 24 h, and 72 h postrace and analyzed for inflammation biomarkers (interleukins [IL] 6 and 10, high-sensitivity C-reactive protein, and leukocytes). URI rates, assessed by the Wisconsin Upper Respiratory Symptom Survey, were compared between the study groups during the 2-wk period after the marathon race. URI was defined if the Wisconsin Upper Respiratory Symptom Survey score was equal or greater than seven, representing either one severe symptom or seven mild symptoms. RESULTS: Immediately postrace, the increase of IL-6 was not significantly different between the WOB and the PL groups (median [interquartile range]: WOB, 33.8 [22.5-58.8] ng·L; PL, 35.6 [24.8-61.29] ng·L; P = 0.758). No significant group differences were observed for increases of IL-10, high-sensitivity C-reactive protein, or leukocytes pre- to postrace (all P > 0.05). From race day until 2 wk after the marathon race, the percentage of individuals with at least one URI did not significantly differ between the groups (WOB, 50.0%; PL, 51.5%; P = 0.859). CONCLUSION: Supplementation with rutoside and hydrolytic enzymes before and after a marathon race did not attenuate postrace inflammation or decrease URI incidence in nonelite male marathon runners.

Chitosan nanoencapsulated exogenous trypsin biomimics zymogen-like enzyme in fish gastrointestinal tract.

Exogenous proteolytic enzyme supplementation is required in certain disease conditions in humans and animals and due to compelling reasons on use of more plant protein ingredients and profitability in animal feed industry. However, limitations on their utility in diet are imposed by their pH specificity, thermolabile nature, inhibition due to a variety of factors and the possibility of intestinal damage. For enhancing the efficacy and safety of exogenous trypsin, an efficient chitosan (0.04%) nanoencapsulation-based controlled delivery system was developed. An experiment was conducted for 45 days to evaluate nanoencapsulated trypsin (0.01% and 0.02%) along with 0.02% bare trypsin and 0.4% chitosan nanoparticles against a control diet on productive efficiency (growth rate, feed conversion and protein efficiency ratio), organo-somatic indices, nutrient digestibility, tissue enzyme activities, hematic parameters and intestinal histology of the fish Labeo rohita. All the synthesized nanoparticles were of desired characteristics. Enhanced fish productive efficiency using nanoencapsulated trypsin over its bare form was noticed, which corresponded with enhanced (P<0.01) nutrient digestibility, activity of intestinal protease, liver and muscle tissue transaminases (alanine and aspartate) and dehydrogenases (lactate and malate), serum blood urea nitrogen and serum protein profile. Intestinal tissues of fish fed with 0.02% bare trypsin showed broadened, marked foamy cells with lipid vacuoles. However, villi were healthier in appearance with improved morphological features in fish fed with nanoencapsulated trypsin than with bare trypsin, and the villi were longer in fish fed with 0.01% nanoencapsulated trypsin than with 0.02% nanoencapsulated trypsin. The result of this premier experiment shows that nanoencapsulated trypsin mimics zymogen-like proteolytic activity via controlled release, and hence the use of 0.01% nanoencapsulated trypsin (in chitosan nanoparticles) over bare trypsin can be favored as a dietary supplement in animals and humans.

[Impact of exogenous proteolytic enzymes on immunogenesis in patients with urogenital infections].

The use of systemic enzyme therapy in combination with antibiotics in the treatment of urogenital chlamydia infection in patients of both sexes proved to improve the therapeutic efficacy and to reduce the risk of the side effects.

[Effects of proteolytic enzyme therapy with Wobe Mugos against chemotherapy-induced toxicity in breast cancer patients - results of a pilot study]. / Proteolytische enzymtherapie mit wobe mugos gegen chemotherapie-bedingte toxizitäten bei brustkrebs-patientinnen - ergebnisse einer pilotstudie.

BACKGROUND: Wobe Mugos(®) is an enzyme preparation containing the proteases trypsin and papain from the pancreatic calf and commonly used in complementary medicine. From non-randomized studies, its multiple favorable effects including the reduction of adverse events from radiotherapy and chemotherapy in oncology patients have been reported. METHODS: Patients with invasive breast cancer receiving adjuvant or palliative chemotherapy between 2005 and 2006 and who were scheduled for at least two further cycles of this specific chemotherapy were included in this pilot study. A specific toxicity of at least grade 2 using the NCI common toxicity criteria which occurred during the preceeding cycle and was relevant to the patient was recorded. This specific toxicity, e.g. grade 2 emesis, was again evaluated after two analogously administered further chemotherapy cycles in which Wobe Mugos(®) had been coadministered. The hypothesis was that specific toxicites of individual patients will be reduced by this enzyme therapy. The majority of the 57 consecutive patients received palliative chemotherapy. Peroral enzyme therapy was coadministered with two uncracked coated tablets three times daily on all days of a chemotherapy cycle except on the day of chemotherapy administration. RESULTS: Tolerability was good. Positive and neutral effects on toxicity parameters were observed in 11 and 42 patients, respectively, and a negative influence in 4 women. CONCLUSION: We observed only a marginal influence of Wobe Mugos(®) in patients with breast cancer who had experienced at least a grade 2 toxicity in the preceding cycle and who received two further identical cycles of this chemotherapy in conjunction with the enzyme preparation. Randomized studies on homogenous patient populations are necessary.

[Effect of flogensim in the treatment of postischemic inflammation (according to results of using interleukin-6 in patients with acute brain infarction)].

I1-6 in blood serum 109 patients with ischemic stroke was tested on 1st and 7 day after developing the disease. The decrease in concentration of I1-6 on 7 day was found after a complex therapy with Flogensim in the study group in comparison with the control group where a traditional therapy was used. The authors found considerable difference in consequences of the ischemic stroke on 21 day among patients pertaining to different group: the number of patients of the study group where results were better increases and number of the patients of this group with no dynamic or even worsening in neurological status decreases.

Oral immunogenicity of the plant proteinase bromelain.

Bromelain is a natural mixture of proteolytic enzymes derived from pineapple stem that has been shown to have anti-inflammatory activity when administered orally. Although most proteins given orally without adjuvant (e.g., food) result in tolerance, we previously reported that long-term oral exposure to bromelain stimulated the development of high serum anti-bromelain antibody titers. The purpose of these studies was to further investigate the mechanisms responsible for the immunogenicity of oral bromelain. Results showed that repeated exposure was required for development of anti-bromelain antibodies, with strong antibody responses in all mice that received at least 12 doses of bromelain either orally or intragastrically over 3-6 weeks. Proteolytic activity was required for strong oral immunogenicity in the absence of conventional adjuvant, with strong serum antibody responses generated against proteolytically active bromelain and trypsin, but not against ovalbumin, lysozyme, or inactivated bromelain. Significantly higher anti-bromelain antibody titers were seen in IL-10-deficient versus wild-type mice, suggesting that simultaneous treatments that decrease IL-10 activity may further enhance systemic antibody responses following oral exposure. The antibodies generated did not affect the proteolytic activity of bromelain. The data demonstrate that proteolytically active antigens such as bromelain can stimulate both systemic and mucosal immune responses following repeated oral exposure. Further studies of the mechanisms involved in generation of immune responses following oral exposure to proteolytically active antigens can lead to a better understanding of mechanisms of oral tolerance and to the development of novel adjuvants for oral vaccines.

Effect of pretreatment of food gluten with prolyl endopeptidase on gluten-induced malabsorption in celiac sprue.

BACKGROUND & AIMS: We sought to determine whether prolyl endopeptidase (PEP) treatment of food gluten would obviate the intestinal dysfunction produced by small amounts of dietary gluten supplement in patients with celiac sprue. METHODS: Twenty asymptomatic patients with histologically proven celiac sprue completed a randomized, double-blind, cross-over study involving two 14-day stages. Each patient consumed a low dose of a gluten supplement daily (5 g; equivalent to 1 slice of bread) in 1 stage and gluten pretreated with PEP in the other stage. Patients completed a daily symptom questionnaire and a D-xylose urine excretion and a 72-hour quantitative fecal fat were monitored before and after each stage. RESULTS: Despite clinical remission at baseline, 40% of patients had at least 1 abnormal celiac antibody, 20% had an abnormal urine xylose, and 63% had an abnormal fecal fat test result. There was no difference in symptoms as a function of the type of gluten consumed. In response to gluten not treated with PEP, an appreciable proportion of patients developed malabsorption of fat (7 of 17, 41%) or xylose (8 of 14, 57%). When the gluten was pretreated with PEP, fat malabsorption was avoided in 5 of 7 and xylose malabsorption in 4 of 8 of these same patients. CONCLUSIONS: A significant proportion of asymptomatic patients with celiac sprue have abnormal celiac antibodies and fat or carbohydrate malabsorption. Pretreatment of gluten with PEP avoided the development of fat or carbohydrate malabsorption in the majority of those patients who developed fat or carbohydrate malabsorption after a 2-week gluten challenge.

Management of radiation dermatitis in a patient after mastectomy.

Women who are diagnosed with breast cancer and undergoing chemotherapy and radiation are at high risk of developing acute radiation dermatitis. The purpose of this case study is to explore an alternative topical therapy for skin toxicity in the post-radiation care of a patient with a history of breast cancer. The patient, a 54-year-old white female, was treated by modified radical mastectomy, chemotherapy, and radiation. During post-radiation therapy the patient developed wet desquamation reaction over the midincision line into the right axilla. Balsam Peru, hydrogenated castor oil, trypsin (Xenaderm Healthpoint, San Antonio, Tex) was trialed to evaluate efficacy in providing wound healing to the denuded skin. Within 14 days of treatment, the area was completely healed and topical therapy stopped. This case study provides the basis for further research into the area of topical therapy for women with moist desquamation after radiation for breast cancer.

[Oral enzyme therapy for chronic hepatitis C--a retrospective analysis]. / Orale Enzymtherapie bei chronischer Hepatitis C -- eine retrospektive Analyse.

BACKGROUND AND OBJECTIVE: Data from a randomized trial in hepatitis C infected Egyptian patients suggest that the oral intake of the enzyme preparation Phlogenzym results in a significant reduction of aminotransferase levels and is equally effective to the therapy with interferon alpha. In our study, we investigated whether comparable effects can be found in daily practice in German patients. PATIENTS AND METHODS: We retrospectively evaluated the aminotransferase levels of all patients with chronic hepatitis C who were treated with Phlogenzym at a dose of 6 tablets/day in our outpatient department between 1998 and 2003. Inclusion criteria for the study were treatment duration >3 weeks and elevated alanine-aminotransferase (ALT)levels 6 months prior to and at the beginning of the treatment with Phlogenzym. Liver cirrhosis Child B or C, interferon therapy within the last 3 months before treatment with Phlogenzym and alcohol intake >30 g/day were exclusion criteria. RESULTS: 22 patients were included into the analyses. The mean duration of treatment with Phlogenzym was 77 +/- 41 days. ALT, aspartate-aminotransferase (AST) and gamma glutamyl transpeptidase (GGT) levels did not change significantly during treatment. Fitting a generalized linear model, we estimated that a hypothetical patient who started with a baseline value of 50 U/I after 90 days of treatment ends up in an ALT level of 52 U/I (95%-CI:27-77 U/I), an AST level of 51 U/I (35-67 U/I) and a GGT level of 42 U/I (22-61 U/I). 5 out of 22 patients had to stop treatment because of side effects. CONCLUSION: 6 tablets Phlogenzym per day do not seem to reduce permanently elevated aminotransferases in patients with chronic hepatitis C.

A randomized, double-blind, placebo-controlled study of oral hydrolytic enzymes in relapsing multiple sclerosis.

Oral administration of hydrolytic enzymes (HE), such as bromelain, trypsin and rutosid, may have beneficial effects on the clinical course of neurological symptoms related to multiple sclerosis (MS). This is supported by a complete protection by HE from experimental allergic encephalomyelitis, an animal model related to MS. Three hundred and one patients with relapsing MS were enrolled in a double-blind, placebo-controlled trial. No treatment effect between the placebo and the HE groups was found either for clinical or MRI parameters.

Oral enzyme combination versus diclofenac in the treatment of osteoarthritis of the knee--a double-blind prospective randomized study.

The aim of this study was to compare the efficacy and safety of an oral enzyme-rutosid combination (ERC) containing rutosid and the enzymes bromelain and trypsin, with that of diclofenac in patients with osteoarthritis (OA) of the knee. A total of 103 patients presenting with painful episodes of OA of the knee were treated for 6 weeks in two study centers in a randomized, double-blind, parallel group trial. Altogether, 52 patients were treated in the ERC group and 51 patients were treated in the diclofenac group. Primary efficacy criteria were Lequesne's Algofunctional Index (LFI) and a 'complaint index', including pain at rest, pain on motion and restricted function. The efficacy criteria were analyzed by applying the Wilcoxon-Mann-Whitney test that provides the Mann-Whitney estimator (MW) as a measure of relevance. Non-inferiority was considered to be proven if the lower bound of the 97.5% one-sided confidence interval (CI-LB) was higher than MW = 0.36 (benchmark of not yet relevant inferiority). Both treatments resulted in clear improvements. Within the 6-week observation period, the mean value of the LFI decreased from 13.0 to 9.4 in the ERC group and from 12.5 to 9.4 in the diclofenac group. Non-inferiority of ERC was demonstrated by both primary criteria, LFI (MW = 0.5305; CI-LB = 0.4171) and complaint index (MW = 0.5434; CI-LB = 0.4296). Considerable improvements were also seen in secondary efficacy criteria, with a slight tendency towards superiority of ERC. The global judgment of efficacy by physician resulted in at least good ratings for 51.4% of the ERC patients, and for 37.2% of the diclofenac patients. In the majority of patients tolerability was judged in both drug groups as very good or good. The current study indicates that ERC can be considered as an effective and safe alternative to NSAIDs such as diclofenac in the treatment of painful episodes of OA of the knee. Placebo-controlled studies are now needed to confirm these results.

A double blind, randomised, parallel group study on the efficacy and safety of treating acute lateral ankle sprain with oral hydrolytic enzymes.

OBJECTIVE: To compare the effectiveness and safety of the triple combination Phlogenzym (rutoside, bromelain, and trypsin) with double combinations, the single substances, and placebo. DESIGN: Multinational, multicentre, double blind, randomised, parallel group design with eight groups structured according to a factorial design. SETTING: Orthopaedic surgery and emergency departments in 27 European hospitals. PARTICIPANTS: A total of 721 patients aged 16-53 years presenting with acute unilateral sprain of the lateral ankle joint. PRIMARY EFFICACY CRITERIA: (a) Pain on walking one or two steps, as defined by the patient on a visual analogue scale. (b) The range of motion, as measured by the investigator and expressed as a sum of flexion and extension. (c) The volume of the injured ankle measured with a volometer. RESULTS: At the primary end point at seven days, the greatest reduction in pain was in the bromelain/trypsin group (73.7%). The Phlogenzym group showed a median reduction of 60.3%, and the placebo group showed a median reduction of 73.3%. The largest increase in range of motion (median) was in the placebo group (60% change from baseline). The Phlogenzym group showed a median increase of 42.9%. The biggest decrease in swelling was in the trypsin group (3.9% change from baseline). The Phlogenzym group showed a -2.30% change from baseline and the placebo group a -2.90% change. In the subgroup analysis of patients who did not use a Caligamed brace, Phlogenzym was superior to placebo for the summarising directional test of the primary efficacy criteria (MW = 0.621; LB-CI 0.496; p = 0.029; one sided Wei-Lachin procedure). The vast majority of doctors and patients rated the tolerability of all treatments tested as very good or at least good. CONCLUSIONS: Phlogenzym was not found to be superior to the three two-drug combinations, the three single substances, or placebo for treatment of patients with acute unilateral sprain of the lateral ankle joint. The small subgroup of patients treated without the support of a Caligamed brace showed evidence of superiority of Phlogenzym over placebo. Further research is warranted to study this effect of Phlogenzym in patients treated without ankle support.

[Proteolytic enzymes as an alternative in comparison with nonsteroidal anti-inflammatory drugs (NSAID) in the treatment of degenerative and inflammatory rheumatic disease: systematic review]. / Proteolytische Enzyme als therapeutische Alternative zu nichtsteroidalen Antirheumatika (NSAR) in der antiphlogistischen Therapie degenerativer und entzündlich-rheumatischer Erkrankungen. Systematischer Review.

BACKGROUND AND PURPOSE: The comparably high number of severe side effects due to treatment with nonsteroidal anti-inflammatory drugs (NSAID) calls for better tolerated substances. One possible alternative is seen in the systemic treatment with proteolytic enzyme preparations for oral administration. The aim of this study was to determine whether the results from controlled randomized trials on enzyme therapy prove equal anti-inflammatory effectiveness compared to NSAID in the treatment of degenerative or inflammatory rheumatic disease. METHODS: All drug preparations registered in Germany as having anti-inflammatory properties were listed. Among these preparations, a systematic search was carried out for randomized clinical therapeutic trials giving evidence for the anti-inflammatory effectiveness of enzyme preparations or their components. RESULTS: The anti-inflammatory effectiveness of three out of eight registered enzyme preparations was investigated in randomized trials. In total, seven trials were judged to be sufficiently documented and to allow valuation. All studies show severe methodical deficits, and the standard trial design (clinical trials during inpatient rehabilitation in combination with extensive accompanying treatment) does not allow clear-cut conclusions. CONCLUSION: According to the present state of knowledge, oral proteolytic enzyme treatment does not offer a justified alternative in comparison with NSAID in the anti-inflammatory treatment of rheumatic disease.

[Effect of phlogenzym in long-term treatment of patients with multiple sclerosis]. / Efektyvnist' flohenzymu pry tryvalomu zastosuvanni u khvorykh na rozsiianii skleroz.

An assessment was carried out of clinical effectiveness of the drug phlogenzym in 74 patients with remitting, remitting-progressive, and secondary progressive course of multiple sclerosis. Phlogenzym intake for up to one to three years resulted in decline in the incidence of complications, with their degree having come to be lower, duration of remissions longer, progression of the illness slowed down. The data secured suggest to us that phlogenzym is a safe agent. It can, we believe used in a therapeutic regimen for those patients presenting with remitting and remitting-progressive types of the course of the disease.

Use of enzyme and heparin paste in acute haemorrhoids.

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.

Administration of proteolytic enzymes bromelain and trypsin diminish the number of CD4+ cells and the interferon-gamma response in Peyer's patches and spleen in endotoxemic balb/c mice.

Recent publications revealed that bromelain exerts a marked effect on T-cell response by inhibiting T-cell signal transduction. These experimental studies may help to explain former clinical investigations showing that Phlogenzym (PHL), a preparation consisting of the proteases bromelain and trypsin and the antioxidant rutosid, ameliorate certain diseases with an underlying inflammatory process. In this study, we showed that orally administered PHL significantly reduced lymphocyte subpopulations in Peyer's patches (PPs) of healthy and endotoxemic mice. Similarly, the number of splenic lymphocytes in endotoxin-boostered mice was significantly lowered by PHL. The effect of PHL was more pronounced on T cells than on B cells leading especially to a diminution of CD4+ cells. Moreover, PHL pretreatment decreased IFN-gamma mRNA in PPs and spleen of endotoxemic mice. These results reveal that PHL may ameliorate inflammatory process by reducing the number of CD4+ cells and by diminishing INF-gamma mRNA levels.

Oral therapy with proteolytic enzymes decreases excessive TGF-beta levels in human blood.

UNLABELLED: Therapy with oral proteolytic enzymes (OET) with combination drug products containing papain, bromelain, trypsin, and chymotrypsin has been shown to be beneficial in clinical settings such as radiotherapy-induced fibrosis, bleomycin pneumotoxicity and immunosuppression in cancer, all of which are nowadays known to be accompanied by excessive transforming growth factor-beta (TGF-beta) production. It has been demonstrated that proteolytic enzymes reduce TGF-beta levels in serum by converting the protease inhibitor alpha2 macroglobulin (alpha2M) from the "slow" form into the "fast" form, whereby the "fast" form binds and inactivates TGF-beta irreversibly. In this study we have investigated the effect of OET on the concentration of TGF-beta1 in serum of patients with rheumatoid arthritis (RA) (n = 38), osteomyelofibrosis (OMF) (n = 7) and herpes zoster (HZ) (n = 7). Seventy-eight healthy volunteers served as controls. TGF-beta1 levels in serum were assessed by enzyme-linked immunosorbent assay (ELISA). We have demonstrated that in healthy volunteers and in patients there exists a correlation between active and latent TGF-beta1 in serum (r=0.8021; P<0.0001). Treatment with OET had no significant effect on TGF-beta1 concentration in healthy volunteers or patients with a normal level of TGF-beta1. In patients with elevated TGF-beta1 concentration (> 50 ng/ml serum), OET reduced TGF-beta1 in RA (P < 0.005), in OMF (P < 0.05) and in HZ (P < 0.05). CONCLUSION: These results support the concept that OET is beneficial in diseases characterized in part by TGF-beta1 overproduction.

[Comparative analysis of various techniques of prostatic drainage in patients with chronic obstructive prostatitis]. / Sravnitel'nyi analiz éffektivnosti razlichnykh tekhnologii drenirovaniia predstatel'noi zhelezy u bol'nykh khronicheskim obstruktivnym prostatitom.

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.