[Effectiveness of pidotimod in combination with bacterial lysates in the treatment of the pfapa (periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis) syndrome]. / Efficacia del Pidotimod in associazione a lisato batterico nel trattamento della syndrome PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis).

AIM: PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis) syndrome is the most common autoinflammatory syndrome in pediatrics, accepted as an hyperimmune condition. Pidotimod is a molecule with immunomodulatory activity on both innate and adaptive immune responses; it also has the capacity to modulate the function of the respiratory epithelial cells through the activation of a NK-KB pathway which would involve the host-virus interaction. Moreover, the proven beneficial effect of Pidotimod in enhancing the immune response during vaccination, and its benefits in the prevention of respiratory tract infections, should be noted. METHODS: A joint combination of Pidotimod and bacterial lysates was used to treat 37 children with a clinical diagnosis of PFAPA; within the end of the first year of therapy, the healing rate of PFAPA symptoms was 67.5% (25 children), with a 10.8% (4 cases) still in complete remission within the end of the second year of follow-up. RESULTS: It is important to highlight that 29 children (78.3%) had benefitted from this therapy, in terms of healing, with a marked decrease in the incidence of fever from a total of 360 to 106 episodes, and episodes of periodic fever occurring almost 4 times less frequently. The use of Pidotimod determined a significant reduction of surgical tonsillectomy's treatment. CONCLUSION: This approach had a strong impact on the children's quality of life; a significant decrement in the use of antipyretic drugs, as well as a lower rate of antibiotic prescription, were also noted. It also had a dramatic impact on families' lives, because the treatment lowers the number of absences of family members from work or school/kindergarten.

[Effects of dihydromyricetin on tumor necrosis factor and NF-kappaB p65 of RAU rats].

OBJECTIVE: To study the effects of dihydromyricetin (DMY) on tumor necrosis factor (TNF-alpha) and NF-kappaB p65 cells of the recurrent aphthous ulcer (RAU) rat. METHOD: Sixty of Sprague Dawley (SD) rats are randomly divided into 6 groups. The rat RAU models was established by injection of immunogen composed of the homogenate supernate of homogeneous oral mucosa from SD rats and Freund's complete adjuvant (FCA) into rat backs subcutaneously once every two weeks for 5 times, and the only FCA injected as normal control. DMY(50,100, 200 mg x kg(-1)) and licorzine (67.5 mg x kg(-1)) were given intragastrically once daily for 7 days on the day of the last immunogen injection, respectively. Water was given instead of drugs in normal and model control groups. The blood was got from the fundus oculi vein of rats on the day after last administration, the serum was separated. Then the rats were put to death with the cervical dislocation and decollated on the ice stage. Two sides of rat buccal mucosal tissue were cut. One side of them was put into 4% neutral formalin and another was added into 10 times of phosphate buffer to homogenize it homogenate. The oral mucosa ulcer occurrence of rats was observed by the histopathology. The content of TNF-alpha in serum and oral mucosa was assayed with ELISA; the expression of NF-kappaB cells was determined by the immunohistochemisty and macrophagus was determined by azure-feosin-dyeing in oral mucosa tissue. The expression of TNF-alpha mRNA in serum and oral mucosa was detected by reverse transcription polymerase chain reaction. RESULT: In RAU rats, oral mucosa ulcer occurred, the content of TNF-alpha raised and the expression of TNF-alpha mRNA increased in serum and oral mucosa, the expression of positive NF-kappaB p65 cells and the amount of macrophages went up in oral mucosa. DMY and licorzine significantly reduced occurrence of oral mucosa ulcer in RAU rats, lowered content of TNF-alpha and the expression of TNF-alpha mRNA in serum and oral mucosa, reduced expression of positive NF-kappaB p65 cells and the amount of macrophages. CONCLUSION: It is considered that DMY could inhibited occurrence of oral mucosa ulcer in RAU rats. One principle of it's effects could be that DMY controlled NF-kappaB p65 regulation on transcription and release of TNF-alpha mRNA in macrophages in oral mucosa ulcer tissue and lead to fall of TNF-alpha content in oral mucosa tissue causing role of anti-oral mucosa ulcer.

[Effect of shuizhongcao granule on cellular immune function of experimental animal with recurrent aphthous stomatitis].

OBJECTIVE: To investigate the effect of Shuizhongcao Granule (SZCG) on cellular immune function in animal model of recurrent aphthous stomatitis (RAS). METHODS: Experimental animal model of RAS were established by immunological method. The modeled animals were randomized into 4 groups, Group A was the model control group, Group B was treated by Levamisole (2.5 mg/mL), Group C and D was treated with high-dose (0.5 g/mL) and low-dose (0.24 g/mL) SZCG respectively. The medication was administered via gastric perfusion, starting from the 7th week of the experiment, and continued for 28 days. Meanwhile, a normal control group was set up. Percentage of T-lymphocyte subsets, CD3, CD4 and CD8, and serum levels of interleukin 10 and 12 (IL-10 and IL-12) in peripheral blood were detected before and after treatment. RESULTS: Percentages of CD3, CD4 and CD4/CD8 ratio in the model control group were 40.50 +/- 7.46%, 30.80 +/- 5.33% and 79.56 +/- 8.32 respectively, all lower than those in the normal control group (P<0.05); level of serum IL-10 was higher (8.02 +/- 0.53 ng/L) and that of IL-12 was lower (15.51 +/- 1.35 ng/L) in the model animal than those in normal control (P<0.05). After treatment, levels of CD3, CD4, CD4/CD8 and IL-12 in Group B were 55.30 +/- 6.33%, 43.50 +/- 5.33%, 99.29 +/- 13.84 and 17.72 +/- 1.70 ng/L, those in Group C were 61.50 +/- 4.32%, 47.20 +/- 4.37%, 103.30 +/- 7.42 and 18.18 +/- 1.54 ng/L, and in Group D were 58.50 +/- 6.03%, 42.80 +/- 3.17%, 110.27 +/- 12.85 and 17.74 +/- 1.96 ng/L, respectively, all were higher than those in Group A, but levels of IL-10 in the three treatment groups were lower than that in Goup A (P<0.05 or P<0.01). CONCLUSION: The immune function of RAS model animals is in the suppressed condition; SZCG can improve the immune suppression to achieve its therapeutic effect on the disease.

"Tien-Hsien liquid" can modulate antigen-stimulated cytokine production by T-cells isolated from patients with recurrent aphthous ulcerations.

Recurrent aphthous ulcerations (RAU) represent a common oral mucosal disease with altered humoral and cellular immunities. Tien-Hsien liquid (THL) is an extract of Chinese medicinal herbs with immunomodulating effects. Our previous study found that THL can modulate the antigen-stimulated proliferative response of peripheral blood mononuclear cells and T-cells isolated from RAU patients. In this study, we further tested whether THL can modulate the antigen-stimulated cytokine production by T-cells isolated from RAU patients. To achieve this goal, T-cells isolated from 19 RAU patients were incubated with phytohemagglutinin (PHA), glutaraldehyde-inactivated tetanus toxoid (TT), glucosyltransferase D (GtfD), or antigens of Streptococcus mutans in the presence or absence of THL. The levels of interleukin (IL)-2, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), IL-6, or IL-10 in the supernatants of T-cell cultures were measured by cytokine enzyme-linked immunosorbent assay (ELISA) kits. We found that THL significantly increased the PHA- or TT-stimulated TNF-alpha, IL-6, and IL-10 production by T-cells isolated from RAU patients. However, THL could also significantly decrease the TT-stimulated IL-2 production, the GtfD-stimulated IL-2, TNF-alpha, IL-6 and IL-10 production, and the S. mutans-stimulated IFN-gamma, TNF-alpha, and IL-10 production by T-cells isolated from RAU patients. These results indicate that THL can modulate the antigen-stimulated cytokine production by T-cells isolated from RAU patients. Because RAU is probably a Thl-mediated disease with elevated levels of IL-2, IFN-gamma, TNF-alpha and IL-6 in either the patient's sera or oral lesions and these increased levels of cytokines can be reduced by THL, we suggest that THL may be a potential immunoceutical agent for treatment of RAU.

Immunomodulating effects of "tien-hsien liquid" on peripheral blood mononuclear cells and T-lymphocytes from patients with recurrent aphthous ulcerations.

Recurrent aphthous ulcerations (RAU) represent a common oral mucosal disease with altered humoral and cellular immunities. In our institution, an immunomodulating agent, levamisole, is used to treat RAU with satisfactory therapeutic effect. Tien-Hsien liquid (THL) is an extract of Chinese medicinal herbs with immunomodulating effects. To test whether THL has immunomodulating effects on antigen-stimulated proliferation response (PR) of peripheral blood mononuclear cells (PBMC) and T-cells isolated from RAU patients and to test whether THL is a potential drug for treating RAU, PBMC or T-cells isolated from RAU patients were incubated with lipopolysaccharides (LPS) from Escherica coli, phytohemagglutinin (PHA), staphylococcal enterotoxin B (SEB), glutaraldehyde-inactivated tetanus toxoid (TT), glucosyltransferase D (GtfD), or antigens of Streptococcus mutans in the presence or absence of THL. We found that THL significantly increased the LPS-stimulated PR of PBMC from active RAU patients, the GtfD-stimulated PR of PBMC and of T-cells from inactive RAU patients, and the S. mutans-stimulated PR of PBMC from inactive RAU patients. However, THL could also significantly reduce the SEB-stimulated PR of PBMC and of T-cells from active RAU patients and S. mutans-stimulated PR of T-cells from active RAU patients. These results suggest that THL can modulate the antigen-stimulated PR of PBMC and T-cells from RAU patients. Therefore, it may be a potential immunoceutical agent for treatment of RAU.

Levamisole and Chinese medicinal herbs can modulate the serum interleukin-6 level in patients with recurrent aphthous ulcerations.

BACKGROUND: Recurrent aphthous ulcerations (RAU) are common oral inflammatory lesions. Interleukin-6 (IL-6) is a pro-inflammatory cytokine that has effects on cellular and humoral immunities. Previous studies have shown that the high serum IL-6 levels in some RAU patients can be reduced by drug treatment. This finding suggests that IL-6 may be a useful marker in evaluating therapeutic effects of RAU. METHODS: In this study, we used a solid phase, two-site sequential chemiluminescent immunometric assay to determine the baseline serum levels of IL-6 in a group of 228 patients with RAU, erythema multiforme (EM), traumatic ulcers (TU), oral submucous fibrosis (OSF), pemphigus vulgaris (PV), or Sjögren's syndrome (SS), and in 77 normal control subjects. Some RAU patients were treated with levamisole plus Chinese medicinal herbs or levamisole only for 0.5-5 months and their serum IL-6 levels were measured after treatment. RESULTS: We found that about 99% of the normal control subjects and the patients with EM, TU, or OSF had a serum IL-6 level within the normal limit of 5.0 pg/ml. However, 24% (48/197) RAU patients, 14% (1/7) EM patients, 43% (3/7) PV patients, and 100% (6/6) SS patients had a serum level of IL-6 greater than 5.0 pg/ml. The mean serum level of IL-6 in patients with RAU (3.6 +/- 3.5 pg/ml, P < 0.001), minor type RAU (2.7 +/- 2.0 pg/ml, P < 0.05), major type RAU (5.2 +/- 4.6 pg/ml, P < 0.001), or herpetiform type RAU (4.1 +/- 3.8 pg/ml, P < 0.01) was higher than that in normal control subjects. The mean serum level of IL-6 in major type (P < 0.001) or in herpetiform type RAU patients (P < 0.05) was higher than that in minor type RAU patients. The mean reduction of serum IL-6 level (10.0 +/- 7.1 pg/ml) in RAU patients after treatment with levamisole plus Chinese medicinal herbs was significantly higher than that (5.1 +/- 3.7 pg/ml) in RAU patients after treatment with levamisole only (P < 0.005), suggesting that the combination therapy is superior to the single therapy of levamisole only. CONCLUSION: We conclude that levamisole and levamisole plus Chinese medicinal herbs can modulate the serum IL-6 level in RAU patients. Although the therapeutic effect of RAU can be assessed by a decrease in the frequency, duration and number of the oral ulcerations, it can also be monitored by a reduction of serum IL-6 level in RAU patients.

[The assessment of the effectiveness of the shark liver oil in recurrent aphthous stomatitis treatment: clinical and immunological studies]. / Ocena skutecznosci leczenia aft nawrotowych olejem z watroby rekina w aspekcie badan klinicznych i immunologicznych.

There is no specific and effective treatment for recurrent aphthous stomatitis (RAS), which is connected with its unexplained etiology. The purpose of this study was to determine the clinical efficiency and immunomodulation of the shark liver oil in treatment of recurrent aphthous stomatitis. Twenty-five patients with severe disease received treatment with shark liver oil during a three-month period. The frequency of occurrence of RAS decreased from 1.56 before treatment to 0.95 after treatment and the number of lesions per month was significantly reduced during the third month of treatment and two months after treatment. During two months after treatment 4 patients had no ulcers and an improvement was exhibited in all except 3 of the remaining patients. The treatment had an influence on some immunological parameters. A better response of neutrophils to OZ and PMA were seen. The B cell and T CD3/HLA DR+ cell percentage returned to normal values. A significantly increased percentage of T cells was observed as compared to the before treatment value. The level of C4 and the hemolytic activity of the complement system decreased after treatment and neared the normal values. The shark liver oil contains compounds that have a positive immunomodulation action and alleviate the course of disease.

[Major aphthous stomatitis (Sutton's disease): etiopathogenesis, histological and clinical aspects]. / Stomatite aftosa major (malattia di Sutton). Etiopatogenesi, quadri istologici ed aspetti clinici.

Major aphthous stomatitis (Sutton's disease) is a clinical variant of recurrent aphthous stomatitis differentiated by its high level of morbidity. It is generally found in areas of non-keratinized mucosa and is characterised by the presence of necrotic giant ulcers accompanied by intense pain. While this pathology has been the subject of molecular studies, its etiopathogenesis is still unknown. The most widely accredited hypothesis is that it represents an immune mechanism, namely the immunological response of mucosa with antigenic anomalies, modulated by altered local reactivity and influenced by triggering factors. After an extensive review of the various etiopathogenetic hypotheses, clinical and pathological aspects, the authors outline a number of therapeutic protocols including the use of topical and systemic cortisone, immunomodulators and alternative therapies like laser and ultrasound, or medications to protect the ulcers. They stress that the lack of etiopathogenetic uniformity precludes any specific treatment.

[Photophoresis of oxolin ointment in combined therapy of patients with chronic relapsing aphthous stomatitis]. / Fotoforez oksolinovoi mazi v kompleksnom lechenii bol'nykh s khronicheskim retsidiviruiushchim aftoznym stomatitom.

Significant improvement of microcirculation and tissue immunity was found in 75 patients with chronic recurrent aphtous stomatitis treated with photophoresis of 0.25% oxolin ointment on the site of the disease focus.

[Clinical and experimental studies on clearing away stomach-heat purging fire and nourishing yin principle in treating patients of recurrent aphthae].

OBJECTIVE: To observe the therapeutic effect of Kouchuangping granule (KCP) on recurrent aphthae and explore its mechanism. METHODS: One hundred and forty-eight patients treated with KCP were observed and compared with 49 patients treated with tripterygii multiglycoside tablet as control in controlling relapse, prolonging intermittent period, improving local symptom and the influence on humoral and cellular immunity. In animal experiment, the effects of KCP on immunologic function, anti-exudation, anti-inflammation and analgesia were studied. RESULTS: The clinical markedly effective and cure rate of the KCP group was 62.8% and the total effective rate was 89.9%, which were significantly higher than those of the control group (40.8% and 75.5%, P < 0.01, P < 0.05). In the KCP group, the intermittent period of aphthous ulcer recurrence was prolonged to 6 months and the local symptoms were markedly improved, the differences were significant as compared with those before treatment and those in the control group (P < 0.01 or 0.05). The KCP showed effects in suppressing humoral immunity and enhancing cellular immunity. Results of experimental study showed that KCP could inhibit the supernormal reaction of cellular immunity to prevent and treat the hypersensitivity caused erosion and ulceration of mucosae, inhibit capillary permeability and WBC migration and abate the 5-hydroxytryptamine (5-HT) and histamine induced local swelling and pain. CONCLUSION: KCP has a significant effect in treating recurrent aphthae, the mechanism might be related with its effect on immunoregulation, anti-inflammation and anti-exudation.

Topical and systemic therapy for recurrent aphthous stomatitis.

The cause of recurrent aphthous ulcers (RAU), the lesions of recurrent aphthous stomatitis, is incompletely understood but appears to involve immune system dysfunction. Treatment options include no treatment, treatment of associated systemic diseases or conditions (eg, celiac sprue, vitamin deficiencies), systemic medications, topical medications, conversion of the aphthous ulcer to a wound, and palliative treatments. The most effective treatments (systemic or topical corticosteroids, thalidomide) involve agents that suppress or modulate immune system function. In general, topical agents are preferred because they have fewer associated side effects; however, inability to obtain adequate contact time may limit their effectiveness. Adjunct pain control is sometimes necessary, either with pain medications or with adherent agents that coat the ulcers.

[Immunomodulating effect of LongoVital in patients with recurrent aphthous stomatitis. 2]. / Immunmodulerende effekt af LongoVital hos patienter med recidiverende aftøs stomatit. 2.

LongoVital (LV) (DK. reg. no. 5178/75) is a herbal-based tablet enriched with recommended doses of vitamins. Peripheral lymphocyte subsets: T-helper/CD4 (OKT4+) and T-suppressor/cytotoxic/CD8 (OKT8+) were studied quantitatively in 31 otherwise healthy patients with minor recurrent aphthous ulceration (RAU) during six months' daily LV intake in a double-blind, randomised, crossover 1-year study. Fourteen had had LV during the first six months (GrA) and 17 LV during the latter six months (GrB). OKT4+ percentages increased significantly during the LV period in both groups (p less than 0.05). OKT8+ percentages increased in both groups, however, only significantly in GrA (P less than 0.05). It is concluded that LV acts as an immunostimulator in patients with RAU and that the increase in T-lymphocyte subsets may account for the previously reported benefit of LV in RAU prevention.

The effects of relaxation/imagery training on recurrent aphthous stomatitis: a preliminary study.

Recurrent aphthous stomatitis (RAS) is one of the most common diseases of the oral mucosa. Although etiology remains unknown, immunological and emotional disturbances have been implicated in the pathogenesis of RAS. No consistently effective therapeutic regimen has been found. The present study investigates the voluntary modulation of RAS employing hypnosis-like relaxation/imagery training procedures. A multiple baseline design was used to evaluate change in frequency of ulcer recurrence. The role of psychological distress, ratings of perceived pain, and hypnotizability in the treatment of RAS were also examined. Results suggest that the relaxation/imagery treatment program was associated with a significant decrease in the frequency of ulcer recurrence for all subjects. Psychological distress was examined for relationship to ulcer recurrence and symptomatic changes with treatment, but no pattern was found. Finally, little support was found for the role of high hypnotic ability in the treatment of RAS.

Immunomodulation by LongoVital in patients with recurrent aphthous ulceration.

LongoVital (LV) (DK. Reg. No. 5178/75) is a herbal based tablet enriched with recommended doses of vitamins. Peripheral lymphocyte subsets: T-helper/CD4 (OKT4+) and T-suppressor/cytotoxic/CD8 (OKT8+) were studied quantitatively in 31 otherwise healthy patients with minor recurrent aphthous ulceration (RAU) during 6 months' daily LV intake in a double-blind, randomized, crossover 1-year study. Fourteen had had LV during the first 6 months (GrA) and 17 LV during the latter 6 months (GrB). OKT4+ percentages increased significantly during the LV period in both groups (P less than 0.05). OKT8+ percentages increased in both groups, however, only significantly in GrA (P less than 0.05). It is concluded that LV acts as an immunostimulator in patients with RAU and that the increase in T-lymphocyte subsets may account for the previously reported benefit of LV in RAU prevention.