(OR6) BIO-NORMALIZER AS A HYPOALLERGIC DRUG

Title  BIO-NORMALIZER AS A HYPOALLERGIC DRUG
Year
Author  A.G.Rumyanzev,L.G.Korkina,  I.B.Afanas’ev
Publisher

 

R6
Bio-normalizer as a hypoallergic drug
Korkina LG, et. Al

 

TRIAL PROTOCOL

(Confidential)

Pilot Clinical Trial (Phase II)

Title:      BIO-NORMALIZER AS A HYPOALLERGIC DRUG

 

Professor A.G.Rumyanze
Director of Russian Institute for
Pediatric Hematology 

Professor L.G.Korkina
Research Supervisor

Professor I.B.Afanas’ev
Organizer Monitor

 

Research Investigators:

Dr. I.B.Deeva, Ph.D.
I.I. Afanas’ev
T.V.Snigeriva
G.Ibragimova

 

Clinical Investigator:

Professor I.B.Reznik, D.Sci., Ph.D

 

 

 

Table of Contents

 

1.0 Checklist for Patient Eligibility and Necessary Information

2.0 Objectives and Rationale

3.0 Background

4.0 Patient Eligibility

5.0 Treatment Plan

6.0 Patient Evaluation

Appendices

A1.0 Case Report Form

A2.0 Consent Form

A3.0 Decision of the Ethics Committee

 

1.0 Checklist for Patient Eligibility and Necessary Information

 

Age between 2-15 years.

Wheezing

Attacks of breathlessness

“Normal” breathing before asthma attacks

Asthma attacks occurring more than one during previous year

Symptom-provoking factors (allergens, irritants, exercise, etc)

Bronchial asthma since less than 5 years

Informed consent explained to and signed by patients/parent.

 

Age between 2-15 years.

Atopic dermatitis

Skin lesions

Symptoms of dermatitis since less than 5 years

Informed consent explained to and signed by patient/parent.

 

 

2.0 Objectives and Rationale

2.1 To determine the hypoallergic effects of Bio-normalizer (BN) on the patients suffering From atopic bronchial asthma

2.2 To determine the hypoallergic effects of Bio-normalizer (BN) on  patients with      allergic dermatitis.

2.3 To study the effects of BN on the free radical status of children with atopic asthma and         allergic dermatitis.

 

3.0   Background

Atopic asthma and allergic dermatitis are inflammatory disease, which are initiated by the intake of an allergen or irritating agents. Although the mechanisms of developing these pathologies are not fully understood, there is a lot of up-to-date important information concerning major stimulating factors. Thus, it has been shown that an inflammatory reaction in the lungs may be mediated by the immunoglobulin E (IgE) [1] which depends on the amount of eosinophils in the peripheral blood [2]. However, it has now been proposed that in both cases free radicals play an important role [3]. Lulich et al. [4] assumed that the released oxygen radical is a primary source of β-adrenergic receptor dysfunction in asthmatic diseased. Indeed Engels et al. [5] have earlier shown that the impairment of the β-adrenoceptor response depends on the release of oxygen radicals from stimulated macrophages. Furthermore, it has been shown [6] that IgE stimulates the superoxide release by monocytes from patients with asthma and rhinitis. Matsuyama et al. [7] showed and important of oxygen radical generation in the rat model of allergic asthma and the induction of MnSOD during the disease development. Jarjour and Calhoun [8] have studied the production of superoxide alveolar cells in 56 patients with asthma as compared with 49 normal controls. It was concluded that worsening of airway obstruction in asthma is associated with increased spontaneous generation of superoxide by the lung leukocytes.

Similarly, an essential role of oxygen radicals has been shown in skin inflammation. Thus, it was found that monocytes of patients with atopic dermatitis are primed for superoxide production. [9] that can explains the overproduction of oxygen radicals during this pathology. Enhanced in vivo superoxide production from rat skin was shown in the case of UV-dependent flouroquinolone-induced dermatitis [10]. Toxic effect of oxygen radicals in skin inflammation enhanced in the presence of iron [11].

Importance of free radical formation in inflammatory processes points out at the possibility of application of antioxidants and free radical scavengers for the treatment of atopic asthma and dermatitis. It is of special interest that N-acetylcysteine (NAC), a widely used mucolytic drug, is simultaneously an effective antioxidant. Among the other anti inflammatory drugs, salicylate, ibuprofen, ketoprofen, and indomethacin are also hydroxyl radical scavengers. Presently, various antioxidants and free radical scavengers are investigated as new anti-inflammatory pharmacological agents. As it was pointed out, a special attention is drawn to N-acetylcysteine (NAC). Thus, Bernard [12] applied intravenous NAC to patients with established adult respiratory distress syndrome (ADRS) and showed that the NAC treatment permitted to increase significantly the diminished plasma and red cell glutathione levels in. these patients. Leff et al. [13] showed that the post insult treatment of rats with NAC decreased IL-1 induced leukocyte influx and lung leak. In the last studies recombinant SOD [14] and lipoic acid [15] were applied for the treatment lung injury and skin inflammation, respectively.

In accord with the above findings, the clinical trial we have studied the hypoallergic effects of Bio-Normalizer, a natural food supplementation, on the patients with atopic asthma and allergic dermatitis. It has previously been shown that BN is a free radical scavenger [16, 17] and a modulator of oxygen radical production by neutrophils and macrophages [18]. These findings suggest that BN may suppress oxygen radical-mediated inflammatory processes in lung and skin.

 

 

References

 

  1. Chang, K.F., Role of inflammation in the hyper reactivity of the airways in asthma. Thorax 41,657-662(1986).
  2. Horn, B.R, Robin, E.D., and Van Kessel, A. Total eosinophil counts in the management bronchial asthma. New Engl. J. Med. 292, 1152-1155(1975).
  3. C.J.A.Doelman and A.Bast, Oxygen radicals in lung pathology. Free Rad.Biol.Med. 9,381-400(1990).
  4. Lulich, K.M, Goldie,R.C, and Paterson, J.W, Beta-adrenoceptor function in asthmatic bronchial smooth muscle. Gen. Pharmacol. 19,307-311(1988).
  5. Engels, F., Oosting, R.S.,and Nijkamp, F.P.,Pulmonary macrophages induce deterioration of guinea pig tracheal beta-adrenergic function through release of oxygen to radicals. Eur.,J.Pharmacol. 111,143-144(1985).
  6. Demoly, P., Vachier, I., Pene, J., Michel, F.B.,Godard, P., and Damon, M., IgE produces monocyte superoxide anion release: correlation with CD23 expression. Comparison of patients with asthma, patients with rhinitis, and normal subjects. J Allergy Clin.lmmunol. 93 (1, Pt.1), 108-116(1994).
  7. Matsuyama, T., Ihaku, D., Tanimukai, T., Uyama, O., and Kitada, O. Superoxide dismutase suppressed   asthmatic response   with inhibition of   manganese   superoxide induction in rat lung. Nippon Kyobu Shikkan.Gakkai Zasshi. 31, Suppl: 139-45 (1993)
  8. Jarjour,N.N. and Calhoun, W.G., Enhanced production of oxygen radicals in  asthma.J.Lab.ClinMed.123 (1), 131-6 (1994).
  9.  Polla, B.S., Ezekowitz, R.A., and Leung, D.J.M., Monocytes from patients with atopic dermatitis are primed for superoxide production. J Allergy Clin. Immunol. ’89(2), 545-552 (1992).
  10. Wada, K., Saniabadi, A.R., Umemura, K., Nakano, M., Ito, T., and Nakashima, M.,Direct measurement of superoxide dependent chemiluminescence from rat skin following UV-dependent fluoroquinolone.-induced dermatitis. Free Rad.BiolMed. 18, 923-927 (1995).
  11. Trenam, C.W., Blake, D.R., and Morris, C.J., Skin inflammation: reactive oxygen species and the role of iron. J.lnvest.Dermatol. 99(6), 675-682 (1993).
  12. Bernard, G.R., N-acetylcysteine in experimental and clinical acute lung injury. Am.JMed. 91, (Suppl.3S), 54S-59S (1991).
  13. Leff, J.A., Wilke, C.P., Hybertson, B.M., Shanley, P.F., Beehler, C.J., and Repine, J.E., Postinsult treatment with N…acetyl-L-cysteine decreases IL-l-induced neutrophil influx and lung leak in rats. Am.J.Physiol. 265 (5, Pt.1), L501-6 (1993).
  14. Davis, J.M., Rosenfeld, W.N., Sanders, R.J., and Gonenne, A., Prophylactic effects of recombinant human superoxide dismutase in neonatal lung injury. J.Appl.Physiol.74 (5), 2234-41(1993).
  15. Fuchs, J. and Milbradt, R., Antioxidant inhibition of skin inflammation induced by reactive oxidants: evaluation of the redox couple dihydrolipoate/lipoate. Skin Pharmacol. 7 (5), 278-84 (1994).
  16. Santiago, L.A., Osato, J.A., Hiramatsu, M., et al. Free radical scavenging action of Bio-catalizer α·r no.11 (Bio-normalizer) and its by-product, Free Rad.BiolMed. 11, 379-383 (1991).
  17. Osato, J.A., Korkina, L.G., Santiago, L.A., and Afanas’ev, I.B., Effects of Bio­ normalizer (a Food Supplementation) on Free Radical Production by Human Blood Neutrophils, Erythrocytes, and Rat Peritoneal Macrophages. Nutrition: An International Journal of Applied and Basic Nutritional Science, in press.
  18. Osato, J.A.,Afanas’ev I.B., Cheremisina, Z,P., Suslova, T.B., Abramova, N.E.,Michalchik, EV., Deeva, I.B.,Santiago,L.A, and Korkina, L,G., Bio-Normalizer as a modular of phagocytosis  and free radical production by murine inflamed Neutrophils and macrophages. Phys. Chem. Biol &Med. (1995), N2.

 

 

 

 

 

 

 

 

 

 

 

LIST OF PATIENTS

 

No

Name

Sex,  Age   (Years)

Diagnosis

1 Volkov S. M (9) Atopic bronchial asthma, the mild form, remission. Atopic dermatitis. Metabolic nephropathy
2 Osmanova 0. F (13) Bronchial asthma, the mixed severe form, multi-relapsed.Post-hypoxic encephalopathy, rehabilitation. Spastic tetra paresis
3 NemchikovD. M (l5) Acute atopic dermatitis, bronchial asthma, the mixed form, multi-relapsed. Allergic rhinitis and sinusitis. Allergy to the grass pollen.
4 Semenov I. M (6) Bronchial asthma, the mixed severe form, unstable remission. Chronic gastritis…
5 KashperovA. M (10) Bronchial asthma, the mixed severe form, unstable remission. Chronic gastritis and cholecystitis.
6 TarakonovaI. F (4) Atopic dermatitis, acute form. Atopic bronchial asthma, the mixed severe form, frequent attacks of breathlessness. Allergic rhinitis
7 Shapochkina A. F (9m) Child eczema. Iron-deficient anemia.
8 Zhiganov A. M (8) Bronchial asthma, the mixed severe form
9. Veselova A F (5) Acute atopic dermatitis, unstable remission
10 Kumerin A. M (l3) Mild bronchial asthma, the mixed form, remission.
11 Nikolko S. M (15) Atopic acute dermatitis localized moderate form. Allergic rhinitis, sinusitis, and conjunctivitis.
12 Borschova T. F (1y, 2 m) Infantile eczema, severe form, infection foci. Polyvalent allergy.
13 Atamanenko E. F (13) Atopic dermatitis, allergic rhinitis.
14 Kholmachev A. M (1y, 5m) Infantile eczema, severe form. Allergy to cow milk proteins.Perinatal encephalopathy. Left side hemiparesis.
15 Savel’ev A. M (3y,5m) Local atopic dermatitis, acute moderate stage.
16 LyzhinD. M (7)M(S) Atopic bronchial asthma, the mixed mild form.
17 OrlovN. M (5) Atopic bronchial asthma, the mixed form, remission
18 Barsukova T. F (10) Atopic bronchial asthma, the mixed moderate form.
19 Zyganov A. M (l3) Atopic bronchial asthma, the mixed acute form.
20 Lazykin N. M (3y 8m) Acute atopic dermatitis, moderate form. Bronchial asthma, the mixed moderate form, unstable remission.
21 Burdina T. F (11) Acute atopic dermatitis, moderate form. Bronchial asthma, the mixed moderate form, Allergic rhinitis.
22 Razumovskii A. M (4) Atopic bronchial asthma, the mixed severe form remission.
23 Matkov A. M (8) Atopic bronchial asthma, the mixed severe form. Local atopic dermatitis, moderate form. Allergic rhinitis andsinusitis.
24 Gravanov A. M (12) Atopic dermatitis, remission. Atopic bronchial asthma, moderate form, remission.
25 Pankratav A. M(8) Atopic bronchial asthma, the mixed severe form. Food allergy
26 Koreshkov V. M(4) Atopic diffuse dermatitis, acute form. Atopic bronchial asthma, the mixed mild form, remission.
27 Androva N. F(5) Local atopic dermatitis, acute form.
28 Shashkin A. M(12) Atopic diffuse dermatitis, acute moderate form
29 Perfil’ev A. M(8) Atopic bronchial asthma, the mixed moderate form. Unstable remission. Allergy to grass pollen. Allergic rhinitis.
30 Legkun G M(4) Atopic bronchial asthma, the mixed moderate form, remission. Children

 

Children with the odd numbers received BN, while those with even numbers do not received it.

TRIAL DESIGN

 

Group 1

Patients with bronchial asthma received BN.

N1        Volkov

N5         Kashperov

N17       Orlov

N19       Zganov

N23       Matkov

N25       Pankratov

N29       Perfil’ev

 

 

Group 2

Patients with atopic dermatitis received BN.

N3         Nemchikov

N7         Shaposhnikiva

N9       Veselova

N11       Nikolko

N13       Atamanenko

N15       Savel’ev

N21       Burdina

N 27      Andronova

 

 

Group 3

Patients with bronchial asthma, who did not, received BN (Control)

N2         Osmanova

N4         Semenov

N8         Zhiganov

N10       Kumerin

N16       Lyzhin

N18       Barsukova

N22       Razumovskii

N30       Legkun

 

Group 4

Patients with atopic dermatitis, who did not received BN (Control)

N6         Tarakanova

N12       Borschova

N14       Cholmachev

N20       Lazykin

N24       Gravanov

N26       Koreshkov

N28       Shashkin

                         

 

 

Frequency of bronchial asthma attack (breathlessness)

Table 1                  The first visit

Frequency of
Attack

          0             1-2             3-5              >5

Group 1
(asthma + BN)

3/7 (43%)

1/7 (14%)

0

3/7 (43%)

Group 3
(asthma –BN)

4/8 (50%)

2/8 (25%)

0

2/8 (25%)

Group2
(dermat.+BN)

Group 4
(dermat.-BN)

 

Table 2                  The second visit

Frequency of
Attack

0

1-2

3-5

>5

Group 1
(asthma + BN)

5/7 (71%)

1/7 (14%)

1/7 (14%)

0

Group 3
(asthma –BN)

4/8 (50%)

3/8 (38%)

0

1/8 (13%)

Group 2
(dermat.+BN)

Group 4
(dermat.-BN)

 

Table 3  The third visit

Frequency of
Attack

          0             1-2             3-5              >5

Group 1
(asthma + BN)

6/7 (43%)

1/7 (14%)

0

0

Group 3
(asthma –BN)

6/8 (75%)

1/8 (13%)

0

1/8 (13%)

Group 2
(dermat.+BN)

Group 4
(dermat.-BN)

 

 

Dynamics of wheezing

 

Table 4

1st visit

2nd visit

3rd visit

Group 1
(asthma+ BN)

5/7 (71%)

2/7 (29%)

0

Group 3
(_asthma – BN)

4/8 (50%)

2/8 (25%)

1/8 (13%)

 

 

Number of necessary weekly β2 agonist puffs

 

Table 5 The first visit

Number of inhalations

0

<3

3-7

>7

Group 1
(Asthma+ BN)

2/7 (29%)

0

1/7 (14%)

4/7 (57%)

Group 3
(Asthma – BN)

4/8 (50%)

0

0

4/8 (50%)

 

 

Table 6 The second visit

Number of
inhalations

0

<3

3-7

>7

Group 1
(Asthma+ BN)

5/7 (71%)

0

0

2/7 (29%)

Group 3
(Asthma – BN)

4/8 (50%)

0

0

4/8 (50%)

 

 

Table 7 The third visit

Number of
Inhalations

0

<3

3-7

>7

Group 1
(Asthma+ BN)

6/7 (86%)

0

0

1/7 (14%)

Group 3
(Asthma – BN)

3/8 (38%)

0

1/8 (12%)

4/8 (50%)

 

 

 

 

FEV1 Dynamics

 

Table 8 Group 1 (Asthma +BN)

                                  No ofpatient               The first visit The second visit The Third visit
FEV1value % ofexpectedvalue FEV1value % ofexpectedvalue FEV1value % ofexpectedvalue
1 2.178 91.0 1.969 81.9 2.090 87.0
5 2.299 82.0 2.486 89.0 2.420 86.6
17 1.450 104.3 1.360 97.8 1.380 99.3
19 1.232 36.7 1.485 44.2 1.562 46.5
23 1.492 46.4 1.511 58.7 1.524 64.5
25 1.144 55.6 1.804 87.7 1.904 92.5
29 1.859 90.4 1.861 92.3 1.863 93.7

 

m ± SD 72.3 ± 25.28                                        m ± SD 81.4 ± 18.9

 

Table 9 Group 3 (Asthma +BN)

                                  No ofpatient               The first visit The second visit The Third visit
FEV1value % ofexpectedvalue FEV1value % ofexpectedvalue FEV1value % ofexpectedvalue
2 1.265 51.3 1.930 37.7 1.518 61.6
4 1.474 86.2 1.089 73.9 1.510 88.3
8 0.572 29.0 1.800 75.1 1.820 77.3
10 2.352 93.7 2.358 94.3 2.362 95.2
16 1.914 83.3 1.923 85.6 1.928 87.3
18 1.389 69.0 1.389 69.0 1.455 75.6

 

m ± SD 68.8 ± 24.7                     m ± SD 80.9 ± 11.9

 

 

In the case of N22 and N30 the determination of FEV1 was impossible due to a small age.

 

 

Table 10 the eosinophil content in the blood of children of Group1 (asthma+ BN)

No of patient

The first visit

The third visit

1

8

6

5

11

10

17

13

9

19

13

11

23

13

14

25

12

7

29

12

9

Table 11 the eosinophil content in the blood of children of Group 3 (asthma – BN)

No of patient

The first visit

The third visit

2

5

7

4

10

4

8

9

7

10

4

3

16

9

8

18

10

6

22

6

5

30

6

5

 

Table 12 The eosinophil content in the blood of children of Group 2 (dermatitis + BN)

 

No of patient

The first visit

The third visit

3

10

8

7

26

23

9

5

2

11

11

8

13

5

2

15

15

17

21

13

4

27

12

10

 

Table 13 The eosinophil content in the blood of children of group 4 (dermatitis-BN)

 

No of patient

The first visit

The third visit

6

11

5

12

31

8

14

13

12

20

5

6

24

3

4

26

9

12

28

7

5

 

Table 14 The IgE content in the serum of children of group 1 (asthma + BN)

No of patient

The first visit

The third visit

1

356

263

5

1547

914

17

391

286

19

322

356

23

301

290

25

325

249

29

243

199

Table 15 The IgE content in the serum of children of group 2 (asthma – BN)

 

No of patient

The first visit

The third visit

2

36

22

4

361

380

8

100

101

10

128

200

16

235

198

18

328

255

22

245

206

30

189

176

Table 16 The IgE content in the serum of children of group 3 (dermatitis + BN)

 

No of patient

The first visit

The third visit

3

292

261

7

2045

275

9

67

73

11

188

203

13

64

61

15

300

202

21

380

246

27

263

187

Table 17 The IgE content in the serum of children of group 4 (dermatitis – BN)

 

No of patient

The first visit

The third visit

6

182

178

12

289

238

14

100

105

20

318

312

24

309

298

26

108

124

28

275

246

 

 

Table 18 Luminol- amplified CL Group 1 (asthma + BN)

N of patient

Spontaneous

1st day

Spontaneous

30th day

Stimulated

1st day

Stimulated

30th day

1

63

20

1320

843

5

400

19

2220

120

17

26

25

266

774

19

12

54

127

2290

23

204

32

1860

390

25

27

17

238

199

29

84

13

972

218

 

Table 19 Lucigenin-amplified CL Group 1 (asthma + BN)

N of patient

Spontaneous

1st day

Spontaneous

30th day

Stimulated

1st day

Stimulated

30th day

1

2

0

81

60

5

7

3

148

28

17

5

2

20

43

19

1

3

11

120

23

4

3

86

30

25

2

3

25

27

29

2

2

105

28

 

Table 20 Luminol- amplified CL Group 3 (asthma – BN)

N of patient

Spontaneous

1st day

Spontaneous

30th day

Stimulated

1st day

Stimulated

30th day

2

13

28

625

502

4

5

61

182

614

8

77

42

483

445

10

113

15

2040

1554

16

42

65

214

312

18

7

17

264

340

22

7

9

226

630

23

9

4554

753

 

Table 21 Luminol- amplified CL Group 3 (asthma – BN)

N of patient

Spontaneous

1st day

Spontaneous

30th day

Stimulated

1st day

Stimulated

30th day

2

2

2

54

40

4

1

3

614

64

8

5

4

36

51

10

4

5

91

102

16

4

6

32

42

18

1

2

29

26

22

1

2

20

65

30

3

4

310

115

 

 

Table 22 Luminol- amplified CL Group 2 (dermatitis + BN)

N of patient

Spontaneous

1st day

Spontaneous

30th day

Stimulated

1st day

Stimulated

30th day

3

80

80

203

220

7

58

3

494

39

9

4

27

224

1175

11

21

52

1256

1396

13

19

30

108

273

15

63

78

270

340

21

75

66

297

1440

27

10

24

118

260

 

Table 23 Lucegenin- amplified CL Group 2 (dermatitis – BN)

N of patient

Spontaneous
1st day

Spontaneous
30th day

Stimulated
1st day

Stimulated
30th day

3

2

3

22

29

7

4

2

52

23

9

1

2

18

84

11

2

3

58

119

13

4

5

19

42

15

2

2

31

40

21

3

6

28

146

27

2

3

15

25

 

Table 24 Luminol- amplified CL Group 4 (dermatitis – BN)

N of patient

Spontaneous
1st day

Spontaneous
30th day

Stimulated
1st day

Stimulated
30th day

6

21

34

268

417

12

73

9

910

186

14

4

6

44

69

20

22

57

138

1219

24

30

51

1290

1230

26

85

29

2550

1209

28

120

50

2608

800

 

Table 25 Luminol- amplified CL Group 4 (dermatitis – BN)

N of patient

Spontaneous
1st day

Spontaneous
30th day

Stimulated
1st day

Stimulated
30th day

6

2

6

16

53

12

9

1

154

15

14

2

3

10

17

20

2

7

16

98

24

5

8

121

152

26

5

8

118

132

28

3

4

230

131

 

Table 26 The GSH and GSSG content (μmol/g Hb) Group 1(asthma +BN)

N of patient GSH
(1th day)
GSH
(30th day)
GSSG
(30th day)

 GSSG/GSH
(30th day)

1 8.8 8.1 0.0065 0.00080
5 9.6 9.1 0.0137 0.00150
17 5.9 8.3 0.0073 0.00088
19 7.6 6.6           -          -
23 7.7 7.1 0.0040 0.00056
25 7.9 9.3 0.0097 0.00104
29 7.7 7.7 0.0092 0.00120

7.9±1.1                    8.0±1.0               0.0084±0.0033 0.00100±0.0003

 

Table 27 The GSH and GSSG content (μmol/g Hb) Group 3(asthma – BN)

N of patient GSH
(1th day)
GSH
(30th day)
GSSG
(30th day)

GSSG/GSH
(30th day)

2 8.1 8.6 0.0127 0.00148
4 7.2 7.5 0.0120 0.00160
8 7.9 8.1 0.0133 0.00164
10 7.8 6.5 0.0127 0.00195
16 6.4 6.4 0.0111 0.00174
18 7.5 8.2 0.0126 0.00154
22 7.5 7.5 0.0137 0.00180
30 8.6 8.1 0.0130 0.00160

7.9 ± 0.6                   7.6 ± 0.8         0.0126±0.0007   0.00167±0.0015

 

Table 28 The GSH and GSSG content (μmol/g Hb) Group 2 (dermatitis + BN)

N of patient GSH
(1th day)
GSH
(30th day)
GSSG
(30th day)

GSSG/GSH
(30th day)

3 5.3 5.3 0.0090 0.00170
7 10.5 6.6 0.0087 0.00132
9 8.3 6.1 0.0133 0.00220
11 7.9 7.2 0.0100 0.00139
13 6.5 8.4 0.0163 0.00194
15 8.7 8.7 0.0077 0.00088
21 6.6 6.8 0.0110 0.00162
27 8.3 6.7 0.0087 0.00130

7.8 ± 1.6                   7.0 ± 1.1         0.0106±0.0029   0.00154±0.0004

 

Table 29 The GSH and GSSG content (μmol/g Hb) Group 4 (dermatitis – BN)

N of patient

GSH
(1th day)
GSH
(30th day)
GSSG
(30th day)

GSSG/GSH
(30th day)

6 6.8 8.6 0.0133 0.00154
12 8.1 7.1 0.0149 0.00210
14 8.7 8.4 0.0191 0.00227
20 5.4 7.7 0.0178 0.00230
24 9.4 7.7 0.0200 0.00260
26 6.3 8.1 0.0205 0.00250
28 7.0 7.0 0.0137 0.00200

7.4 ± 1.4                   7.8 ± 0.6         0.0170±0.003   0.00219±0.0004

 

 

Table 30 Dynamics of skin pruritus

1st visit 2nd visit 3d visit
Group 2

(dermatitis+BN)7/8 (88%)6/8 (75%)2/8 (25%)Group 4

(dermatitis-BN)4/7 (57%)3/7 (43%)3/7 (43%)

 

 

Table 31 Dynamics of excoriation

1st visit 2nd visit 3d visit
Group 2
(dermatitis+BN)
8/8 (100%) 7/8 (88%) 3/8 (38%)
Group 4
(dermatitis-BN)
5/7 (71%) 5/7 (71%) 3/7 (38%)

 

Table 32 Score of a skin lesion square*

1st visit 2nd visit 3d visit
Group 2
(dermatitis+BN)
22/40 (55%) 18/40 (45%) 12/40 (30%)
Group 4
(dermatitis-BN)
12/35 (34%) 8/35 (23%) 8/35 (23%)

 

* It was assume that score 1 corresponds to one lesion including a facial, a hand lesion, a foot lesion and a trunk lesion. Thus, a total score for one patients is 5; so a total possible score for Group 2 (8 patients) is 40 and that for Group 4 (7patients) is 35.

 

Table 34 Antihistamine drug requirement

1st visit 2nd visit 3d visit
Group 2
(dermatitis+BN)
2/8 (25%) 4/8 (50%) 2/8 (25%)
Group 4
(dermatitis-BN)
4/14 (28%) 4/7 (57%) 4/14 (28%)

 

Table 35    The content of methemoglobin (MetHb) and plasma antioxidant activity

(AOA)                             Group l (asthma + BN)

No. of patient MetHb (%)
(1th day)
MetHb (%)
(30th day)
AOA
(1th day)

AOA
(30th day)

1 30.0
5 2.4 8.9 36.5 20.0
 17 5.0  10.3 21.8 31.3
 19 27.2 23.5 32.3 12.3
23 19.5 21.4 -1.9 1.7
25 21.9 23.4 25.4 25.3
29 21.0 12.9 22.3 12.7

 

Table 36    The content of methemoglobin (MetHb) and plasma antioxidant activity

(AOA)                    Group 2 (dermatitis + BN)

No. of patient MetHb (%)
(1th day)
MetHb (%)
(30th day)
AOA
(1th day)
AOA
(30th day)
2 14.2 9.8 18.3 14.2
4 21.3 21.3 14.5 10.5
8 23.5 23.9 40.1 42.8
10 36.8 8.5 10.6 11.5
16 8.6 16.5
18 18.7 19.0
22 9.4 0.0 38.8 36.8
30 13.9 12.2 26.6 20.6

 

Table 37   The content of methemoglobin (MetHb) and plasma antioxidant activity

(AOA)               Group 2 (dermatitis + BN)

No. of patient MetHb (%)
(1th day)
MetHb (%)
(30th day)
AOA
(1th day)
AOA
(30th day)
3 12.8 13.3
7 35.4 10.4 22.0 29.8
9 10.7 18.6 13.5 14.3
11 18.1 21.5 13.3 17.5
13 8.8 10.9 28.4 19.6
15 13.3 39.8
21 3.3 9.0 45.3 9.1
27 10.9 20.6 21.4 24.5

 

Table 38   The content of methemoglobin (MetHb) and plasma antioxidant activity

(AOA)               Group 4 (dermatitis – BN)

No. of patient MetHb (%)
(1th day)
MetHb (%)
(30th day)
AOA
(1th day)
AOA
(30th day)
6 22.4 10.4 52.7 48.8
12 28.6 25.0 40.1 46.6
14 27.6 19.5
20 6.6 12.3 2.8 28.1
24 20.9 14.0 25.2 26.3
26 12.4 11.8 22.0 14.6
28 19.2 12.8 16.7 15.9

 

 

 CONCLUSIONS

 

One month Bio-Normalizer administration significantly decreased the frequency of bronchial asthma attacks and the b2-agonist requirement of children who suffered from atopic bronchial asthma.

The course of BN therapy suppressed skin lesions and other symptoms of atopic dermatitis and decreased the requirement in steroid ointment applications.

 

There were two drop outs from the dermatitis group due to worsened clinical symptoms in children with severe food allergy after 3-5 days of the trial.

 

BN administration significantly improved children’s antioxidant systems (superoxide dismutase and catalase activities, and glutathione methabolism).