Research on Enzymes and Bacteria
last updated 8.25.05
Below are some selected studies on digestive enzymes and bacteria.

Preparation Wobenzym in the treatment of gonorrhea aiming to improve the results of antibacterial therapy

Chartmane, Ilona - Clinical Center of Skin and Sexually Transmitted Diseases, Riga
Mikazans, Ingmar - Department of Dermathovenerology, Lithuanian Medical Academy

A lot of investigations showed that disfunctions of immune system and nonspecific factors of organism resistence play a significant role in pathogenity of gonorrhea (1, 3, 4, 5, 6, 7, 9). Antibacterial therapy is not always able to prevent deflections of immune system when process of gonorrhea proceeds fast, with complications, becomes chronic,or in the case of relapses of the disease (2, 6, 7, 8, 9, 10). This fully supports the use of enzyme therapy in the treatment of gonorrhea.

Our aim was to investigate and compare basic factors of cell and humoral immunity in patients suffering from gonorrhea treated with antibacterial agents together with enzyme preparations.
According to several authors enzymes increase the effect of antibacterial agents in blood when administered concomitantly. Systemic enzyme therapy significantly influences immune system - ensures homeostasis, antiedematic and analgetic effects, and fybrinolytic processes. Wobenzym effects cell and humoral immunity. Enzymes contribute to normalization of fagocytary activity, lymphokinins production, activity of macrophages and natural killers, regulation of cytokines, function of T lymphocytes subpopulations, decomposition of immune complexes, activation of complement, and synthesis of IL-1 and IL-6 (11).

We determined:
1. Content of T lymphocytes OKT3+ and their subpopulations of T helpers (OKT4+), T suppressors (OKT8+), and (OKT4+/OKT8+) ratio in peripheral blood
2. Content of important factors of humoral immunity - immunoglobulins A, G, M and circulating immune complexes (CIC) in peripheral blood

Material and methods
In our Center two groups of 15 patients suffering from gonorrhea were treated. 6 cases with accute form of the disease and 9 cases with chronic form were included in the first (control) group. 7 cases with accute form and 8 cases with chronic form were included in the second (enzyme) group. All patients were men at the age of 15-36 years. Concomitantly with gonorrhea trichomoniasis was diagnosed in 4 patients, chlamydiosis in 4 patients, ureaplasmosis in 2 cases, and candidosis in 7 patients in the first group. In the second group trichomoniasis was diagnosed in 6 patients, chlamydiosis in 4 patients, ureaplasmosis in 3 cases, and candidosis in 6 patients. All patients were immunologically examined before and after treatment. Using monoclonal antibodies (Reinherz et al., 1979) the content of T lymphocytes OKT3+ and their subpopulations of T helpers (OKT4+), T suppressors (OKT8+), and (OKT4+/OKT8+) ratio in peripheral blood were determined during the treatment. Content of immunoglobulins A, G, M was determined (method of radial immunodifusion in the gel by Mancini et al. (1978), Baranovskis, Rudiks (1982)) using 3.75% solution of polyethylenglycol with spectrophotometric method.

All patients were divided into two groups:

1. First group obtained antibacterial treatment* (* Accute gonorrhea - patients obtained a single dose of 250 mg of Rocephin at the beginning of therapy followed by administration of Norfloxacin - 400 mg two times a day for 5 days, Chronic gonorrhea - with relapses - patients obtained the same antibiotics, Norfloxacin was administered for 10 days, without relapses - patients obtained only Norfloxacin - dosage 400 mg two times a day for 14 days) and 0.5g of natrium nucleinate and 0.5g of methyluracil as a immunostimulator 3 times a day for 14 days.

2. Second group was administered with the same antibiotics as the first group and with Wobenzym 5 tablets 3 times a day.

Control group included 15 healthy volunteers

In both observed group significant deflections were observed before treatment. Inhibition of the cell immunity were found in 13 patients of the first group and in 12 patients of the second group. Average level of OKT4+ was decreased (36.7 + 1.7 and 37.6 + 0.3 p< 0.01), OKT8+ level was increased (26.8 + 2.8 and 28.4 + 3.1 p< 0.05), and coefficient OKT4+/OKT8+ was decreased (1.36 + 0.18 and 1.32 + 0.2 p< 0.00).
A significant increase in average factors IgA (4.13 + 0.82 and 3.9 + 1.2 p< 0.01, in the control 2.5 + 0.03) was also found in both groups, whereas factors IgG and IgM remained within the norm.

Before treatment the CIC value was determined in the serum. In both groups of patients with gonorrhea an increase of CIC was found (30.1 + 0.7 and 31.2 + 1.6 p< 0.001) compared to control (10.8 + 0.4). Increase of IgA and CIC in peripheral blood reflected the disturbances of humoral immunity in 11 patients. This was a reason for the application of systemic enzyme therapy. Repeated examination after the treatment showed significant dynamics in immunologic processes. In the second (enzyme) group the coefficient OKT4+/OKT8+ reached the normal level (1.7 + 0.2 p< 0.01). IgA level remained statistically significantly increased (3.14 + 0.36 and 3.9 + 1.2 p< 0.01).

Determinations of CIC content showed a tendency to decrease in enzyme group (15.6 + 1.2 p< 0.001). Normalization of immune parameters during the enzyme treatment was reached in 12 cases out of 15.

1. Significant disturbances of the cell and humoral immunity were found in gonorrhea patients.
2. Systemic enzyme therrapy (Wobenzym) normalized immune status of gonorrhea patients.
3. Wobenzym can be successfully used to increase the efficacy of gonorrhea therapy.

1. Changes of the ratio OKT4+/OKT8+ as a result of the treatment of patients with gonorrhea
Group Number OKT3+ p OKT4+ p OKT8+ p OKT4+/OKT8 p
Control 15 63.6+0.3 46.2+0.7 25.7+0.4 1.82+0.5
1. group
before treat. 15 52.5+3.7< 0.02 36.7+1.7< 0.01 26.8+2.8< 0.05 1.36+1.8< 0.001
after treat. 15 59.9+1.2< 0.01 36.9+1.9 25.0+0.8 1.4+0.1
Wobenzym group
before treat. 15 53.9+2.1 37.6+0.3< 0.01 28.4+3.1< 0.05 1.32+0.2< 0.001
after treat. 15 61.1+1.0 45.1+2.0 26.3+1.2 1.7+0.2< 0.01
p - compared to control

2. Changes of immunoglobulins A, G, M and CIC in blood of patients with gonorrhea as a result of the treatment
Group Number CICrel. units p IgA g/l p IgG g/l p IgM g/l p
Control 15 10.8+0.4 2.5+0.03 13.8+0.29 1.43+0.29
1. group
before treat. 15 30.1+2.7< 0.001 4.13+0.82< 0.01 15.7+1.6 1.67+0.12
after treat. 15 26.8+2.9< 0.001 3.14+0.36< 0.01 16.1+3.0 1.52+0.8
Wobenzym group
before treat. 15 31.2+1.6< 0.09 3.9+1.2< 0.01 14.8+1.8 1.7+1.2
after treat. 15 15.6+1.2< 0.001 3.9+1.2< 0.01 14.0+3.7< 0.01 1.37+0.23

1. Bygdeman S., Danielsson D. et al.: Gonococcal W serogroups in Scandinavia. A study with polyclonal and monoclonal antibodies. Acta Pathol. Mikrobiol. Immunol. Scandinavia (B), 1983, 91, pp. 293-305.
2. Bygdeman S., Gillenins E.C. et al.: Comparison of two different sets of monoclonal antibodies for the serological classification of Neisseria gonorrhoae. In: G.K. Schoolmin, et al. The pathogenic Neisseria. Washington, DC: American Society for Microbiology, 1985, pp. 31-36.
3. Bygdeman S.: Polyclonal and monoclonal antibodies applied to the epidemiology of gonococcal infection. In: H. Young, A. McMillan, eds.: Immunological diagnosis of sexually transmitted diseases. New York: Marcel Dekker Inc. 1988, pp. 117-185.
4. Coghill D.V., Young H.: Serological calssification of Neisseria gonorrhocae with monoclonal antibody coagulation reagents. Genitourin. Med. 1987, 63, pp. 225-232.
5. Hook E.W., Holmes K.K. et al.: Analysis of the antigen specifity of the human serum immunoglobulin to immune response to complicated gonococcae infections. Infect. Immun. 1984, 43, pp. 706-709.
6. Hook E.W., Holmes K.K.: Gonococcal infections. Ann. Int. Med. 1985, 102, pp. 229-243.
7. Hook E.W., Handsfield H.H.: Gonococcal infections in the adult. In: K.K. Holmes, P.A. Mardh, P.F. Sparling, P.J. Wiesner, eds. Sexually transmitted diseases. McGrowhill, 1990, pp. 149-165.
8. Sherrard J., Barlow D.: Gonorrhoea in men - clinical and diagnostic aspects. Genitourin. Med. 1996, 72, pp. 422-426.
9. Adimora Adamora A.: Sexually transmitted diseases. Mc Hill Book Company, 1994, pp. 25-40.
10. Mikazans I.: Rocefina liotosana gonorejas arstesana. Latvijas arsts 1996, pp. 619-620.
11. Mazurova V., Lila A., Sternina J.: Sistemiska enzymterapija (krievu val.). Petergurga 1995, pp. 27-43.

Systemic enzyme therapy in dermatology and venerology: perspectives of its use.
Protsenko T.V.
State Medical Uiniversity, Donetsk, Ukraine
Zurnal dermatologii i venerologii 1998: 2(6), 12-13.

255 patients (36 – chlamydiosis, 46 –lues, 43 – psoriasis, 48 – sclerodermia, 35 – various forms of alopecia, 25 – granuloma anulare, 22 – lipoid necrobiosis) were observed for more than 2 years. Especially important was a complex treatment of chlamydiosis and lues patients combined with Wobenzym. Patients received Wobenzym 5-3 dragees 3 times a day in combination with conventional antibacterial therapy. SET enhanced significantly therapy efficacy, in some cases even enabled to omit conventional drugs. Patients suffering from dermatological diseases received Wobenzym (9-15 dragees daily for at least 4 weeks) and Wobe-Mugos ointment locally. A marked improvement of clinical symptoms and laboratory parameters was seen in 61.5% patients, improvement in 19.8%.
No side-effects were reported in all 255 patients.

The use of WOBENZYM® to facilitate interferon synthesis in the treatment of chronic urogenital chlamydiosis
Sukhikh G.T., Loginova N.S., Faizullin L.Z., Zdanov A.V, Malinina E.V, Bozedomov VA.
Scientific Center of Obstetrics, Gynecology and Perinatology of the Russian Academy of Medical Sciences and the International Institute of Biological Medicine, 117815, 4 Oparin Street, Moscow, Russia.
Int. J. Immunotherapy XIII(3/4) 131-133 (1997)
Int J Tiss Reac XIX (1/2), 1997 - abstracts of 7th Interscience World Conference on Inflammation, Antirheumatics, Analgesics, Immunomodulators, May 19-21, Geneva, Switzerland

Chlamydial infections are recognized as a major cause of infertility in couples and different types of pathology of male and female reproductive functions. Female endocervical smears and male urethral swabs were examined by polymerase chain reaction (PCR) in 3,200 patients. Optimal schedule of treatment of chronic urogenital chlamydiosis using proteolytic enzymes (peroral tablet of Wobenzym®, Mucos Pharma, Geretsried, Germany) were proposed by us. In order to realize the mechanism of the therapeutic effect of proteinases we investigated the changes in the interferon system of patients. We found significant decrease of IFN a-g production and increase of serum IFN. Application of Wobenzym® led to normalization of leukocyte capability to synthesize IFN in response to all inductors. Standard antibiotic therapy led to chlamydia elimination in 61 % women and 45% men; combination of antibiotic therapy with Wobenzym® resulted in 92% cases with women and 89.5% with men, respectively. The blockade of interferon synthesis by leukocytes seems to be the cause of long-term prolongation of chlamydial infection inducing inflammation in the genital tract. Proteinases coming into the blood relieve the blockade of non-specific antibacterial defense. Thus, proteolytic enzymes were shown as a highly efficient strengthening factor for antibiotic therapy of urogenital chlamydiosis.

Systemic enzyme therapy in the treatment of chronic salpingitis and infertility
Ivaniyta L.I., Ivaniyta S.O., Kornatskaya A.G., Belis N.I., Kondratiyk
Institute of Pediatrics, Obstetrics, and Gynecology, Ukraine
Farm. Zh. (Kiev) 2: 89-92 (1998)

30 women, mean age 26.5 years, with chronic salpingitis and infertility were observed. 18 women suffered from primary infertility, 12 from secondary one. 21 patients were previously treated (antiinflammatory, hormonal therapy). 27 patients were diagnosed with unilateral salpingitis, 3 with bilateral one. Treatment started after activation of chronic inflammatory process. First, pyrogenal was administered, followed by antibacterial, anticandidous, desensibilization, and vitamin therapy. Together with antibiotics, Wobenzym was administered at the dose of 5 dragees 3 times a day for 10 days. Patients in the control group received the same therapy without Wobenzym. Already after 5-6 days of Wobenzym treatment, an improvement of patients' condition was observed. Frequency and intensity of abdominal pain and in 86.4 % normalization of body temperature, appetite and intestinal function was seen. Positive changes of inflammatory signs were found after treatment - decreased infiltration, disappearance of pain on palpation. Positive status was verified also by blood parameters: leukocyte count decreased from 8.0 ± 0.3 x 109 to 6.3 ± 0.1 x 109. Sedimentation normalized and concentration of C-reactive protein decreased under Wobenzym treatment. Above described parameters did not change in the control group. In 20 out of 22 patients, normalization of microflora was found. Impaired menstrual cycle normalized in 75 % patients.

Use of Phlogenzym® in the treatment of secretory otitis in the outpatient practice
Veldová Z., Martínková R., Maderová S.
Audiocentrum Praha
Congress of the Czech Society of Otorhinolaryngology and Surgery of Head and Neck, September 9-11, 1999, Hradec Králové, Czech Republic

Chronic secretory otitis is a special type of middle ear inflammation causing very often conductive hearing loss, thus showing a negative influence on a speech development in preschool children. The authors present their first experience with the preparation Phlogenzym in secretory otitis conservative treatment. Phlogenzym is a combined enzyme preparation showing antiedematous, antiphlogistic, fibrinolytic, and immunomodulatory effects.

26 children were included in the follow-up (group E - enzyme). They received Phlogenzym in addition to the conventional treatment for 3 months. 16 patients receiving the same conventional treatment previously formed a control retrospective group (group K).

Tympanometric curve was normalized completely in 60 % of patients of the group E in comparison with 25 % of the group K. The threshold of air conduction (conductive component oh hearing loss) was decreased in the group E by 35 %, compared to 25 % in the group K. In the case of failed conservative medicamentous treatment an operative treatment was necessary only in 7.7 % of the group E patients in comparison with 25 % of the group K. Moreover, the test of phonematic hearing according to Škodová was evaluated in 12 children of the group E. It showed a significant shift of perception of distinctive speech sound features (voiced x voicedless). A positive influence of therapy occurred in 83 % (of 12 children). Thus, Phlogenzym appears as a suitable part of complex conservative secretory otitis treatment, improving its efficiency.

Efficacy and safety of phlogenzym--a protease formulation, in sepsis in children.

Shahid SK, Turakhia NH, Kundra M, Shanbag P, Daftary GV, Schiess W. LTMMC and LTMG Hospital and Medical College, Mumbai.
J Assoc Physicians India. 2002 Apr;50:527-31. PMID: 12164403

BACKGROUND: Infections are a major cause of hospitalisation wherein the host mounts an inflammatory response against the infecting agent. Administration of proteolytic enzymes could regulate the host's immune system and help early recovery from sepsis.

OBJECTIVE: To test the efficacy and safety of an oral enzyme formulation, Phlogenzym (Mucos Pharma GmbH, Geretsried, Germany; constituents of each enteric-coated tablet were bromelain 90 mg, trypsin 48 mg, rutin 100 mg) as adjuvant therapy in treatment of sepsis in children.

SUBJECTS AND METHODS: Double-blind, randomised, controlled phase III study at a tertiary care centre wherein 60 eligible children aged one month to 12 years with sepsis were randomised to receive either phlogenzym (n=30; 17 boys) or placebo (n=30; 22 boys) tablets (1 tablet/10 kg body weight up to maximum six tablets a day in two or three divided doses for 14-21 days) along with appropriate antibiotics and supportive treatment.

RESULTS: Median time taken for fever to subside was three days (range 1-12; 95% CI--1.14 to 7.14) in the phlogenzym group vs four days (range 1-18; 95% CI--3.52 to 11.52) in the placebo group (p < 0.05); haemodynamic support was needed for two days (range 1-3; 95% CI--0.84 to 3.16) in the phlogenzym group but three days (range 1-8; 95% CI--0.76 to 5.24) in the placebo group (p < 0.05). The modified Glasgow coma scale score normalized in three days (range 1-14; 95% CI--4.62 to 9.62) in the phlogenzym group vs 5.5 days (range 1-18; 95% CI--2.52 to 13.52) in the placebo group (p > 0.05). Oral feeds could be started in four days (range 1-15; 95% CI--1.74 to 9.74) in the phlogenzym group vs five days (range 1-11; 95% CI--1.26 to 11.26) in the placebo group (p > 0.05). Two patients died in the placebo group.

CONCLUSION: Phlogenzym is effective as an adjuvant with antibiotics and supportive treatment for early improvement of pediatric patients with sepsis.

Papain protects papaya trees from herbivorous insects: role of cysteine proteases in latex.

Plant J. 2004 Feb;37(3):370-8 PMID: 14731257
Konno K, Hirayama C, Nakamura M, Tateishi K, Tamura Y, Hattori M, Kohno K.

Many plants contain latex that exudes when leaves are damaged, and a number of proteins and enzymes have been found in it. The roles of those latex proteins and enzymes are as yet poorly understood. We found that papain, a cysteine protease in latex of the Papaya tree (Carica papaya, Caricaceae), is a crucial factor in the defense of the papaya tree against lepidopteran larvae such as oligophagous Samia ricini (Saturniidae) and two notorious polyphagous pests, Mamestra brassicae (Noctuidae) and Spodoptera litura (Noctuidae). Leaves of a number of laticiferous plants, including papaya and a wild fig, Ficus virgata (Moraceae), showed strong toxicity and growth inhibition against lepidopteran larvae, though no apparent toxic factors from these species have been reported. When the latex was washed off, the leaves of these lactiferous plants lost toxicity. Latexes of both papaya and the wild fig were rich in cysteine- protease activity. E-64, a cysteine protease-specific inhibitor, completely deprived the leaves of toxicity when painted on the surface of papaya and fig leaves. Cysteine proteases, such as papain, ficin, and bromelain, all showed toxicity. The results suggest that plant latex and the proteins in it, cysteine proteases in particular, provide plants with a general defense mechanism against herbivorous insects.



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