Streptokinase in Gerontology
PREVENTION AND TREATMENT OF MALE PREMATURE AGEIN BY STREPTOKINASE (SK)
Janis  Zalkalns, professor, president of Latvian Gerontology and Geriatrics
Pavels Ivdra, doctor-urologist, Riga clinical hospital "Gailezers"
Ilona Hartmane, associate professor

Janis Zalkalns
 Pavels Ivdra
 Ilona Hartmane

 

Gerontology (geriatrics) is the branch of research and practice which deals with the ageing issues in the medical context.

Physiological ageing (another name: normal ageing) is a genetically programmed body change, developing with the age despite diseases, and the impact of pathological environment from outside and inside.

Premature ageing is the ageing which is proceeding faster than it normally should. Pathological ageing is premature ageing due to diseases and pathological environment.(1,2,3)

Gerontological population (other names: the elderly, the aged) comprises those people whose relative chronological or premature ageing sets in around > 65 years. For the elderly men, prostatitis in the 3rd – 4th inflammatory stages is one of the diseases which provokes premature pathological ageing.

2060 chronic antibiotic-resistant prostatitis patients, aged 13-82 years, were treated with streptokinase at the Urology unit of Riga clinical hospital from 1981 – 2002.The elderly patients had been observed and treated for years, undergoing a repeated enzyme therapy course with SK almost every year.

Patients with premature pathological ageing are characterized by depression of fibrinolytic and proteolytic enzyme system activity which is manifest in the form of dyscoagulaemia, hypercoagulaemia and thromboembolic complications.(4) Due to dyscoagulaemia and hypercoagulaemia, patients are indicated SK, which is used as fibrinolytic enzyme system plasminogen activator for a longer time, each year regularly.

 

 

Clinical case. (Table Nr 1)

Patient A.R.
From the age 61-78, during 1985-2000 (for 16 years) was repeatedly treated by streptokinase 12 times. Prior to hospitalisation at the Urology unit, the patient was admitted to the intensive care unit because of lung artery thrombemboly.

Clinical diagnosis:
1.Chlamydial prostatitis and paraprostatitis.
2. Inflammation of urogenital venous plexus – phlebothrombosis of small pelvis.
3. State after lung artery thrombemboly.
4. Pneumofibrosis (after lung tuberculosis).
5. Hypercoagulaemia.
6. Antibiotic-resistance.
7. Premature pathological ageing.

At the start of enzyme therapy, the patient was receiving SK from 5 000 – 15 000 e.u. a day for 35 days, totally 255 000 e.u. Due to allergy to SK, one could not indicate larger SK doses, therefore the patient got fibrinolysin extra for 36 days, totally 3 920 000 e.u. and heparin 25 000 u. a day.

Despite the minimum dose of SK course – 255 000 u., antistreptase titre reached 3 000 a.u. in 1 ml plasma. Inflammatory signs in the prostate gland and small pelvis regressed. The period of 2 years remission followed and desensibilisation to SK. Allergy to SK disappeared. Due to the relapse of chlamydial prostatitis in 1988, a repeated enzyme therapy course with SK was introduced in the doses of 250 000 – 2 500 000 e.u. i/v for 30 days. As a result of desensibilisation, the total dose of SK course reached 44 625 000 e.u. The next remission period lasted again for 1 year.

Due to threats of premature, pathological ageing, hypercoagulaemia and thromboembolic complications, the patient was receiving a regular 3rd enzyme therapy course with streptokinase (SK) for 30 days with SK dose 40 500 000 e.u. and antistreptokinase titre 2 400 a.u. in 1 ml plasma. During next 10 years the gerontological patient was receiving 9 enzyme therapy courses with SK (table Nr 1). With each new enzyme therapy course, the dose of SK course was decreased to 5 000 000 – 2 500 000 e.u., but the antistreptase titre got stabilized at the natural background level, 50 – 300 a.u. in 1 ml plasma.

The first to use streptokinase in the treatment of chronic inflammatory disease, i.e. chronic prostatitis in Riga 7th clinical hospital, were professors V. Purmalis, P.Ivdra and professor I.Silins, the proof of it being a certificate for the patent of invention (issued by the USSR) Nr 10066604, in 1984 (5).

P.Ivdra, professor V.Purmalis and E.Smiltens reported on the results of the treatment of chronic prostatitis at the USSR 3rd All-union congress of Unrologists held in Minsk in 1984 (6).

SK is an enzyme drug of microbiological origin – a plasminogen activator which is and will be the main and most available drug of fibrinolytic group. Sources of SK are boundless, production costs are low, since meat broth, whey or hemolytic streptococcal pure culture,etc. are serving as culture medium.

In the view of immunologists, streptokinase is an antigen, which, if introduced i/v, causes the antibody formation. Streptokinase (SK), in the view of biochemists and enzymologists, is an enzyme – streptococcal peptidase A. Antibodies to SK may reach individually the utmost level and concentration, not causing any complications.

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In cases of inflammatory prostate diseases, the antistreptokinase titre, i.e.the positive dynamics of antibody level and the concentration can be considered as a sanogenous response and safe prognosis for the convalescence. The dynamics of SK antibodies, mentioned before, were discovered and published in 1986 by V.Korzans, P.Ivdra, V.Purmalis and J.Prombergs – a certificate for the patent of invention (issued by the USSR) Nr 1237213 (6).

30% of chronic antibiotic-resistant chlamydial prostatitis patients, when treated by SK, do not form antibodies to SK and remain at the natural background level from 50 – 150 a.u. in 1 ml plasma. The immune system of these patients has lost the ability to recognize a strange agent – antigen SK.

The patient group (38%), mentioned here, has a different pathogenetic mechanism, since fibrinolytic activation is not directly proportional to SK dose.

Treating gerontological patients for years and using SK repeatedly, we have found a possibility to stop the ageing processes and to achieve the regression of male pathological climax (4).

Gerontological patients, suffering from antibiotic-resistant chlamydial prostatitis and paraprostatitis, were diagnosed humoral immune deficit, when regularly introducing SK-antigen i/v, there did not form antibodies and the immune system did not give an adequate response. These patients are hard to treat and the course of treatment is usually long.

During the course of enzyme therapy with SK, the antibody level in 42% of patients with chlamydial prostatitis increases from 50 a.u. till 1 000 – 3 000 and more a.u. in 1 ml plasma. Patients of this group have a marked dynamics of antistreptokinase titre with antibody induction, synthesis and accumulation level and the following elimination possibilities at the end stage of the enzyme therapy course. The patient’s immune system responds to intravenously introduced antigen – SK by formation of adequate antibodies. Thus, only less than half – 42% of chalmydial prostatitis patients have not lost the ability to recognize intravenously introduced antigen – SK and to respond by formation of sufficient number of antibodies. The greater is the increase of antistreptase titre in dynamics, the better are the possibilities of sanation, which is controversal to the regularities of thrombolytic therapy.

In case of chlamydial reinfection or a relapse, if the patient has received SK therapy before (months or years ago), one can not uncommonly observe a positive dynamics of antistreptase with an intensified antibody formation, but later with the following, lasting antigen-specific response loss and secondary SK antibody formation blockage.

Doctors P.Ivdra, A.Miltins, professor V.Purmalis, J.Prombergs of Riga 7th clinical hospital were the first to discover secondary-induced SK antibody formation blockage and this priority was registered as a patent Nr 1534785 (issued in the USSR) DSP 05.05.88. Doctor P.Ivdra reported on the peculiarities of antistreptase titre dynamics at the 4th All-union Urologists’ congress in Moscow in 1990. (7,8)

Clinical case (Table Nr 2)

Patient V.J.,
61 yrs.old, hospitalized in the Urology unit, treated for antibiotic-resistance and premature pathological ageing for 31 days.

Complaints:
Difficulties of urination, a poor (thin) urine stream. Libido and potency are definitely low. Pain in the sacral region and in both thighs. Several venous nodules of inflammatory signs in the left shank.

Case history:
Prostatitis of 20 years duration. The patient has been treated ambulatory and 4 years ago at the Urology unit. The last remission period – 4 years. Due to antibiotic-resistance the current therapy without streptokinase appeared to be ineffective. Before the enzyme therapy, the coagulogram showed a marked hypercoagulaemia. 2nd type antibodies of Herpes simplex virus – positive.

Clinical diagnosis: 
1. Premature pathological ageing.
2. HSV -2 prostatitis and paraprostatitis.
3. Inflammation of urogenital venous plexus.
4. Hypercoagulaemia.
5. Antibiotic-resistance.
6. Dystrophic spondylosis of L1-L5 vertebrae with a skeletal pain syndrome.

The patient received 30 day long enzyme therapy course with SK in the doses from 5 000 – 750 000 e.u. Due to allergic reaction to SK, the treatment with streptokinase was begun in small doses and gradually reached 750 000 u. a day during 30 day course. The total SK dose was 14 825 000 e.u. Antibodies to SK increased from 6 00 – 1 800 a.u. in 1 ml plasma and began to decrease to 1 600 a.u.

After the enzyme therapy course with SK, coagulaemia regressed, inflammatory signs in the prostate regressed as well. Remission stage was achieved. Period of remission – 7 months. Repeated enzyme therapy course with SK in doses from 25 000 – 750 000 e.u. with the total course dose was 8 510 000 e.u. On the 15th enzyme therapy day the patient’s coagulogram showed a marked fibrinolysis with bleeding from the sites of needle pricks and subcutaneous hematomas. SK infusion was cancelled for 1 day. Next day the enzyme therapy was continued with very small doses of SK from 10 000 – 25 000 – 50 000 without heparin. Coagulogram normalized. Antistreptokinase titre 100 a.u. in 1 ml plasma was constant. Secondary-induced SK antibody formation blockage was achieved (Table Nr 2) (Case history Nr 1659).

Next remission period – 1 year. For prevention of premature pathological ageing process, a repeated enzyme therapy course with SK was introduced with 25 000 – 250 000 e.u. Coagulogram indices were retained at hypocoagulaemic threshold level. Antistreptase titre 100 a.u. in 1 ml plasma was at natural background level. It indicated the longstanding blockage of antistreptokinase formation. With each following enzyme therapy course the SK doses were decreased but plasminogen fibrinolytic activation was growing.

Conclusion:

When treating the elderly people, one should try to achieve streptokinase antibody formation blockage and the increase of spontaneous fibrinolytic activity. The tests mentioned are objective and testify the stoppage of the ageing process and positive sanogenous reaction.

The outcome of the treatment of gerontological patients is assessed considering the patient’s feelings, coagulogram indices, antistreptokinase titre dynamics, chlamydial antigen structures and the elimination of antibodies, palpatory findings of the prostate and the reduction of daily and course doses of plasminogen activator – SK.

The faster and in a greater amount the antibodies to SK are forming, the better is prognosis. By reaching a patient’s individual maximal antistreptokinase titre level in 1 ml plasma, the antibody formation stops and their elimination sets in. Such a streptokinase titre dynamics is considered a sanogenous reaction.

It is characteristic that the antibody titre is increasing much slower than it is in thrombolytic therapy cases.

Positive sanogenous reaction in patients with premature pathological ageing depends on SK antibody level and concentration in blood but not so much on the dose of plasminogen activator – streptokinase.

For a great number of gerontological patients, even minimal SK doses may be effective. Increase of fibrinolytic activity is the main criterion of routine enzyme therapy, though it is hard to prognose beforehand how much SK will be needed and how long the enzyme therapy course will be.

Clinical case. (Table Nr 3)

Patient M.D., aged from 53-73 yrs.
From 1984 – 2002 (for 18 years)he was 8 times repeatedly treated with streptokinase, fibrinolysin and heparin.

Clinical diagnosis: 
1. Premature pathological ageing (at the age of 53 yrs.).
2. Calculous chlamydial prostatitis and paraprostatitis.
3. Antibiotic resistance.
4. Chronic calculous cholecystitis.
5. Deformative spondylosis with skeletal pain syndrome of lumbar part of the spine.

Enzyme therapy course – 18 days of the year with SK doses from 100 000 – 250 000 e.u., in total 3 025 000 e.u. Because of side effects, such as hyperpyrexia, arthralgias, abdominal pain syndrome, fibrinolysin (in 1984) was indicated instead of SK in the duration of 16 days, in total 440 000 u. and heparin 12 500 – 25 000 u. a day. Simultaneously the patient was administered antichlamydial antibiotics. Antibodies to SK grew to 400 a.u. in 1 ml plasma. One year long remission period followed. 35 days long repeated enzyme therapy course with SK from 250 000 – 5 000 000 e.u. a day with a total course dose 26 400 000 e.u. was undertaken. Antistreptokinase titre increased to 1 000 a.u. in 1 ml plasma.

Next remission period – 2 years. Urogenital chlamydiosis reinfection followed and an exacerbation of chlamydial prostatitis. Repeatedly the enzyme therapy course was indicated with SK from 250 000 – 2 million e.u. a day for the 3rd time. The total SK dose of the 3rd course reached 36 300 000 e.u.,but antistreptokinase titre instead of the expected increase decreased to 300 a.v. in 1 ml plasma.

Starting with the 4th enzyme therapy course, SK dose diminished to 5 000 000 e.u. and next 8 years the antistreptokinase titre did not change, remaining constant 100 – 50 a.u. in 1 ml plasma at the natural background level. During 18 years of therapy, a stable hypocoagulaemia on relatively small plasminogen activator doses was achieved by applying SK. Once again premature pathological ageing was prevented. As a result of antibiotic enzyme therapy, prostatitis and paraprostatitis completely regressed. Skeletal pain syndrome disappeared. Coagulogram normalized. SK antibody formation blockage was achieved, giving a possibility to treat with relatively small SK doses, decreasing enzyme therapy costs. There is a chance to administer etiopathogenetic enzyme therapy to suffering men in cases of premature pathological ageing.


Conclusions:

1. Inflammatory diseases of prostate and other genital organs are the main reasons for premature pathological ageing in the etiopathogenesis.

2. In the treatment of premature pathological ageing, starting the 1st enzyme therapy course with SK, there may develop allergic, anaphylactic reactions even with small SK doses and not uncommonly the doctors refuse the enzyme therapy because of the risk of eventual side effects.

3. Patients with premature pathological ageing whose immune systems do not have an adequate response to i/v SK – antigen and who do not form antibodies to SK are hard to treat and treatment is long since their etiopathogenetic mechanism of the disease is different.

4. Antistreptokinase titre dynamics and SK doses are objective differentially diagnostic tests, which give orientation possibilities for premature pathological ageing enzyme therapy.

5. Treatment of premature pathological ageing processes is optimal, if regularly, year by year (10-15-20), at least 1-2 times a year, the antirelapse enzyme therapy course with streptokinase is repeated.

6. Peculiarity of premature pathological ageing enzyme therapy is that it should be done for 10-13-15 years, regularly year by year, or in case SK i/v infusions are repeated after 1 year; in such a case one can achieve normalization of fibrinolytic activity even with relatively small SK doses, despite the antistreptokinase titre level.

7. SK dose, antistreptokinase titre dynamics and the length of the treatment are objective differentially diagnostic tests, as well as criteria which allow to judge about sanogenous reaction of the enzyme therapy and the regression of premature pathological ageing processes.

8. In cases of premature pathological ageing, when treating with SK, antistreptokinase titre positive dynamics can be considered a sanogenous reaction and positive prognosis of convalescence.

9. During a repeated enzyme therapy with SK, high antistreptokinase titre is rarely the cause of anaphylactic complications.

10. In 38% of cases when treating with SK, the antibodies to SK do not form and remain within the borders of natural background, but allergic and anaphylactic reactions are not more common than they are in patients with high antistreptokinase level.

11. Antistreptokinase titre negative dynamics require to indicate urokinase or plasminogen activator (t-PA) extra to SK, and then to indicate SK repeatedly in individually maximal doses.

12. Only 42% of chronic chlamydial prostatitis patients have normal SK antibody induction, synthesis and accumulation possibilities. Reaching the maximal antibody level, their elimination sets in already at the enzyme therapy end stage.

13. The bigger is SK antibody level rise, the better are the sanogenous possibilities.

14. In cases of reinfection or relapse, when treating with SK, one can observe and register SK antigen-specific reaction loss and secondary induced SK antibody formation blockage.

15. SK antibody rise in premature pathological ageing patients up to the maximal level is comparatively longstanding, on average 15-30 days and determines the length of the enzyme therapy course.

16. The enzyme therapy course with SK in premature pathological ageing patients can be stopped only when SK antibody formation and concentration has reached the individually maximal level, has stopped and the antibody elimination has begun. In opposite case, there is the threat for inflammation relapse.

17. In the treatment of premature pathological ageing it is advisable to repeat the antirelapse enzyme therapy course with SK at least once a year.

18. By achieving SK antibody induction and synthesis (formation) blockage, relatively small SK doses allow to achieve longstanding fibrinolytic activation effect.

19. Normalization of fibrinolytic activity is the basic task of the enzyme therapy of premature pathological ageing. 

Literature:

  1. Encyclopedia of Gerontology; Age, Aging, and the Aged.
    Birren E.J., Marshall V.W. (Eds.) New York, 1996.

  2. Hazzard W.R. Principles of geriatric Medicine and Gerontology.
    London, 1999.

  3. Horan M.A., Pendlton N. The relationship between ageing and disease.
    Reviews in Clinical Gerontology, 1995; 5; 125-141.

  4. Pavels Ivdra, Edvins Platkajis. Usage of Tissue Plasminogen Activator in treatment of Men pathological Climacteric and Prostatitis. http://www.expo.lv/gailes/prostatitis.htm

  5. V.R.Purmalis, P.P.Ivdra, I.A.Silinsh
    "Sposob lecenia hroniceskogo prostatita streptokinazoi"
    Avt.svid.SSSR No.1066604, opublikovano 15.01.84, bjul. No.2

  6. V.A.Korzans, P.P.Ivdra, V.R.Purmalis,  J.B.Prombergs
    "Sposob lecenia hroniceskogo prostatita"
    Avt.svid.SSSR No.1237213, opublikovano 15.06.86, bjul. No.22

  7. P.P.Ivdra, A.P.Miltinsh, V.R.Purmalis, J.B.Prombergs
    "Sposob lecenia urogenitalnogo hlamidioza"
    Avt.svid.SSSR No.1534785, ot 05.05.88

  8. P.P.Ivdra  "Antitelogenez antitel k streptokinaze pri enzimoterapiji oslozhneenih form hronicheskogo prostatita", Materiali IV Vsesojuznogo sjezda urologov 10-12 oktjabrja 1990.g., Moskva

  9. Ivdra P.,Platkajis E.,Geldners I. Indications for enzyme therapy with streptase, urokinase and tissue plasminogen activator t-PA in chlamydial prostatitis, 1998. http://www.expo.lv/gailes/prostatitis.htm

  10. Platkajis E., Ivdra P., Miltins A., Geldners I., Ancupane I
    Clinical value of dynamics of streptokinase antibody level in antibiotic-resistant chlamydial prostatitis patients during enzyme therapy with streptokinase. 1999. http://www.expo.lv/gailes/streptokinase.htm

  11. Ivdra P., Zilevica A., Miltins A., Ancupane I. Role of tissue plasminogen activator (t-PA) in enzyme therapy of antibiotic-resistant chlamycial prostatitis. Riga, 1999. http://www.expo.lv/gailes/actilyse_prostatitis.htm

  12. Ivdra P., Purmalis G., Geldners I. Streptokinaze ka plasminogena aktivacijas inhibitors. I Latvian Congress of Surgeons. May 29 – 20, 2000. Theses and poster report. 2000.01.16. http://www.expo.lv/gailes/viagra_streptase.htm

  13. P.Ivdra, G.Purmalis, A.Zilevica, I.Geldners, J.Zalkalns, I.Ancupane, A.Miltins. Streptokinase as plasminogen activation inhibitor for chlamydial prostatitis patients. Riga, latvian Association of Physicians-Chlamydiologists, 2000. http://www.expo.lv/gailes/streptokinasel.htm

  14. P.Ivdra, J.Zalkalns, A.Zilevica, I.Ancupane, I.Geldners, E.Baumanis. Multidisciplinary problems in choosing proteolytic enzymes and their activators for enzyme therapy of antibiotic-resistant and urogenital chlamydiosis. Riga, Latvia, http://www.expo.lv/gailes/enzyme.htm

  15. J.Zalkalns, P.Ivdra, A.Zilevica, G.Purmalis, I.Ancupane, I.Geldners. Possibilities of enzyme therapy in pain syndrome sedation in patients with infectious spondylosis of urogenital origin and spondylarthrosis (01,05.07) http://www.expo.lv/gailes/pain-syndrome.htm

  16. J.Zalkalns, P.Ivdra, A.Zilevica, I.Ancupane. Specificity of enzyme therapy in treatment of late inflammatory forms of prostatitis (02.03.01) http://www.expo.lv/gailes/enzyme1.htm.

 


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