Therapeutic effects of 5,2'-dibromo-2,4',5'-trihydroxydiphenylmethanone (LM49) in an experimental rat model of acute pyelonephritis by immunomodulation and anti-inflammation.

Antibiotics are still the primary therapy for acute pyelonephritis (APN); rarely, natural polyphenols are also used. LM49 is a novel marine bromophenol derivative displaying strong anti-inflammatory effects. We investigated the therapeutic efficacy of LM49 in an experimental rat model of APN. The model was established by injecting 0.5 mL Escherichia coli (ATCC 25922, 108 CFU/mL) into the urinary bladders of Sprague Dawley rats. This model showed increased kidney viscera indices and renal bacterial growth scores, as well as pathological changes in kidneys. We also performed a broth microdilution antimicrobial susceptibility test of the E. coli strain. Both norfloxacin and LM49 treatment reduced kidney viscera indices and decreased microbial counts in urine cultures and kidney homogenates in APN rats. However, in vitro experiments showed that LM49 did not directly inhibit bacteria. Rather, LM49 treatment inhibited inflammatory cell infiltration or abscess and improved tissue lesions in the renal medullary junction, renal pelvis, and calyx, and high-dose LM49 treatment inhibited the production of inflammatory interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) in serum. CD4+ T cells were higher in the LM49 groups treated with high, medium, and low doses than in the model group, whereas only high-dose LM49 treatment increased the number of CD8+ T cells, as compared with that in the model group. However, LM49 treatment did not influence hematological parameters. Our results show that LM49 therapeutic effects in an APN animal model may be achieved by regulating immune responses and inhibiting inflammatory mediators, suggesting it as a candidate APN treatment.

[The nephroprotective potential of peloid therapy used for the rehabilitation of the patients presenting with chronic pyelonephritis]. / Nefroprotektivnyi potentsial peloidoterapii v reabilitatsii bol'nykh khronicheskim pielonefritom.

This review article presents the data on the mechanism of action of peloid therapy from the perspective of its defibrosing effect, the structure and functions of the extracellular matrix under the normal and pathological conditions. In addition, role of this treatment modality in the progression of tubulointerstitial fibrosis which determines the severity and prognosis of chronic pyelonephritis is considered. The researchers are currently carry out the extensive studies aimed at the search of the methods for the primary and secondary prevention of chronic pyelonephritis. A wide range of pharmacotherapeutic modalities are currently used for this purpose. Moreover the development of long-acting anti-relapse medications is currently underway along with the further improvement of high-tech reconstructive surgical methods for the intervention on the organs of the urinary system. At the same time, the nephroprotective potential of the natural physical factors, such as therapeutic muds, e.g. peloids, remains poorly explored even though their well apparent thermophysical properties, unique organic and mineral composition, and saturation with biologically active compounds are well known long ago. The systemic response to peloid therapy manifests itself as the changes in the metabolism of the intercellular matrix and collagen of the connective tissue associated with the alterations in the process of fibrogenesis and the development of tubulointerstitial disorders. The direct and indirect influence of peloids on the connective tissue is possible. The indirect effects are attributable to the peloid impact on the antioxidant status, immunity, hormonal regulation, and metabolic processes. These findings suggest the necessity of the relevant experimental and clinical studies for the evaluation of the influence of peloid therapy on the structure and metabolism of the connective tissue in the kidneys including dynamics of the markers of inflammation, proliferation and fibrogenesis, and the hormonal status of the patients suffering from chronic pyelonephritis based on the application of the modern technologies in accordance with the requirements of evidence-based medicine.

[USE OF PHYTOTHERAPY IN COMBINATION TREATMENT OF CHRONIC PYELONEPHRITIS].

The present paper reports results of a comparative study of 48 patients with latent chronic pyelonephritis and 3-18 years of duration of the disease. Patients assigned to group 1 (n=23) received standard treatment. In patients of group 2 (n=25) standard treatment was supplemented by the administration of 30-day course of Kanferon N 2 dragees twice daily. Kanferon N supplementation was found to be effective as an anti-inflammatory-measure due to its positive impact on renal microcirculation and urinary bacterial composition. It reduces the level of proinflammatory cytokines, stimulates humoral and cellular immunity thus preventing further disease progression.

[Potentials of phytotherapy in the complex treatment of acute pyelonephritis].

The purpose of this study was to increase the effectiveness of treatment of patients with acute pyelonephritis by incorporating of phytopreparation "Prolit Super Septo" in complex therapy. The study included 38 patients with acute primary pyelonephritis. All patients have received standard medical therapy, 21 of them (Group 2) have additionally received "Prolit Super Septo" 2 capsules 2 times a day for 1 month. Outcome measures included basic laboratory parameters, and results of bacteriological examination and immunological assessment of patients 12-14 and 28-30 days after initiation of therapy. Against the background of the therapy, positive dynamics of the level of leukocyturia and bacteriuria was detected in both groups; therapeutic effect, however, was more pronounced in the Group 2 treated with complex therapy: after the end of treatment, the proportion of sterile cultures was 85.7%, whereas in Group 1--70.6%. In addition, complex treatment had a positive effect on the immune status of patients, as evidenced by normalization of blood immunoglobulins, circulating immune complexes and C-reactive protein. The inclusion of "Prolit Super Septo" in the complex conservative treatment of patients with acute pyelonephritis promotes the development of an adequate immune response and the rapid elimination of the pathogens, thus preventing the development of purulent forms of the disease, or chronization of process.

[Clinical-biochemical and immunological parameters in the diagnosis and treatment of chronic pyelonephritis on the background of intercurrent diseases].

Studies have shown that complicated chronic pyelonephritis in the active phase is characterized by structural and functional instability cytomembranes and decreased immunological resistance of the patient man. Supplement standard antibiotic treatment with ozone therapy antioxidant immunomodulation drug thus received immunobiochemical study.

[POSITIVE EFFECTS OF MODERN IMMUNOCORRECTION ACCORDING TO THE ANALYSIS OF CYTOKINES AND SLPI IN PATIENTS WITH PYELONEPHRITIS].

The peculiarities of cytokines as compounds of immunogenesis are shown in the patients having acute (A) and chronic (Ch) pyelonephritis (PN). The combination of antibacterial therapy with Nukleinat and Galavit promotes the positive changes of cytokin-producing ability of immunocompetent cells and decrease in the level of proinflammation cytokines in blood and urine, secretory leucocyte protease inhibitor (SLPI) in urine. In children with PN and adult patients with diagnostically elevated titres of antibodies (IgG) to Herpes simplex virus, Cytomegalovirus are shown the positive effects of Kanephron® H and Proteflazidum, accordingly. Clinico-immunological effects of immunomodulators testify to the expediency of this usage in complex therapy with the aim to modulate the cytokine link of immunity for improvement of the effective treatment in APN and the protection against aggravation of kidney functioning in ChPN.

Immunopathological and antimicrobial effect of black pepper, ginger and thyme extracts on experimental model of acute hematogenous pyelonephritis in albino rats.

Recent studies showed prominent antimicrobial activity of various plant extracts on certain pathogenic microorganisms, therefore we prepared crude aqueous extracts of black pepper, ginger and thyme and carried out an in vitro study by measuring antimicrobial activity of these extracts using the agar well diffusion method. An in vivo study was carried out on 50 adult healthy male albino rats which were divided into 5 groups, 10 rats each. Group 1: negative control group which received saline solution intragastrically daily; Group 2: Positive control group, injected with mixed bacterial suspension of S.aureus and E.coli as a model of pyelonephritis, then received saline solution intragastrically daily; Group 3: injected with the same dose of mixed bacterial suspension, then received 100 mg/kg/day black pepper extract intragastrically; Group 4: injected with mixed bacterial suspension then received 500 mg/kg/day ginger extract intragastrically. Group 5: injected with mixed bacterial suspension then received 500 mg/kg/day thyme extract intragastrically. All groups were sacrificed after either 1 or 4 weeks. Serum and blood samples were collected for lysozyme activity estimation using agarose lysoplate, measurement of nitric oxide production, and lymphocyte transformation test as well as for counting both total and differential leukocytes and erythrocytes. Kidney samples were tested histopathologically. Both in vivo and in vitro results confirm the efficacy of these extracts as natural antimicrobials and suggest the possibility of using them in treatment procedures.

[The combined treatment of patients presenting with chronic pyelonephritis with the use of magnetolaserotherapy].

The present study included 70 patients (mean age 36.0 +- 1.5 years) presenting with chronic pyelonephritis. Thirty of them were given magnetolaserotherapy in addition to the conventional treatment. Their immune status as well as the levels of proinflammatory cytokines (interleukin-1 bets, interleukin-6, and tumour necrosis factor-alpha) were determined. It is shown that the combined treatment (basal therapy and magnetolaserotherapy) caused a significant decrease in the duration of the main clinical manifestations of the disease and normalization of the immune system and cytokine production.

[Clinicobiochemical and immunological assessment of polyoxidonium efficacy in the treatment of patients with chronic calculous pyelonephritis].

Of 59 patients with chronic calculous pyelonephritis (CCP) taking preparation therapy for extracorporeal lithotripsy, 29 patients received combined basic treatment (antibacterial drugs, phytotherapy, physiotherapy) plus polyoxidonium (a course of 10 intramuscular 6 mg injections each other day). The rest 30 patients (controls) received basic therapy alone. Polyoxidonium efficacy was assessed by the results of clinical, device and immunological investigations, content of the main phospholipid fractions and cholesterol in red cell membranes. The results of the tests show that polyoxidonium has anti-inflammatory and immunomodulating effects, exhibits activity of peroxidation processes, contributes to normalization of a lipid phase of cell membranes and can be recommended as a component of combined treatment of patients with chronic pyelonephritis and urolithiasis.

[Interference currents in combined therapy of chronic pyelonephritis in children].

Investigations performed by the authors proved pathogenetic validity of interference therapy of chronic pyelonephritis in children. A course of interference currents has a positive effect on partial renal functions, excretion of beta2-microglobulin, urodynamics of the lower urinary tract, humoral and cell links of immunity, lipid peroxidation in red cell membranes. Advantages of interference currents impact on the reflex-segmentary zone and urinary bladder projection area in children with concomitant neurogenic dysfunction of the urinary bladder are shown.

[The role of uric acid in effects of balneotherapy on the phagocytic link of immunity and unspecific defense at the Truskavets health resort]. / Rol' sechovoï kysloty v efektakh bal'neoterapiï na kurorti Truskavets' ta ïï vplyv na fahotsytarnu lanku imunitetu ta nespetsyfichnyi zakhyst.

Revealed in the wake of balneotherapy at the Truskavets health-resort were two opposite types of changes--those in the level of uriacidemia and in the content of theophylline-sensitive lymphocytes that are probably caused by central and peripheral effects of uric acid. In this setting, parameters characterizing the phagocytic link of immunity and unspecific defense are noted to change unidirectionally, in other words, they remain unaffected by changes in uriacidemia.

[Clinical immunological study on prevention and treatment of chronic pyelonephritis with yishenkang granule].

OBJECTIVE: To investigate the relationship between chronic pyelonephritis (CPN) and immune function, and the therapeutic mechanism of Yishenkang granule (YSKG). METHODS: One hundred and twenty patients of CPN were divided into 3 groups randomly, the YSKG group (treated with YSKG), the control A group (treated with Sanjin tablet) and the control B group (treated with western medicine). Serum levels of immunoglobulin (Ig), complement 3 (C3), interleukin-2 (IL-2), peripheral T-lymphocyte subsets, and urinary secretory immunoglobulin A (sIgA) were determined before and after treatment with monoclonal antibody assay, agar diffusion method, radioimmunoassay (RIA), and radioimmuno-equilibrium method, and compared with normal control. RESULTS: There were disorders of T-lymphocyte subsets in CPN, lowering of serum Ig, C3 and urinary sIgA, and increase of blood IL-2 (P < 0.05 or P < 0.01). These abnormalities could be normalized after YSKG treatment. CONCLUSION: Functional disorders of cellular and humoral immunity exist in CPN patients of chronic stage, YSKG could correct the immune functional disorder, control the recurrence of CPN effectively and alleviate the immunopathological damage.

[The effect of Velikobagachanskaia mineral water on the course of chronic pyelonephritis]. / Vliianie velikobagachanskoi mineral'noi vody na techenie khronicheskogo pielonefrita.

The employing of Velikobagachanskaia mineral water internally by drinking and externally by taking a bath with it adds to the effectiveness of treatment of chronic pyelonephritis, modulates parameters associated with immune homeostasis, reduces the number of carriers of antibodies to M. hominis, facilitates prolongation of clinical and laboratory remission.

[The use of laser radiation and sinusoidal modulated currents in the therapy of patients with chronic calculous pyelonephritis]. / Primenenie lazernogo izlucheniia i sinusoidal'nykh modulirovannykh tokov v terapii bol'nykh khronicheskim kal'kuleznym pielonefritom.

The authors present a technique of treating chronic calculous pyelonephritis with laser radiation and sinusoidal modulated currents which promotes a complete elimination of the calculus fragments in 100, 70 and 50% of the patients in the stone size 0.2-0.5 cm, 0.5-0.7 cm and > 7 cm, respectively. This combined therapy had also antiinflammatory, and immunity-stimulating effects.

[The local immunity of the urinary system in patients with recurrent urolithiasis]. / Sostoianie mestnogo immuniteta mochevoi sistemy u bol'nykh s retsidivnym urolitiazom.

51 patients with urolithiasis complicated by pyelonephritis in the active phase of inflammation were studied for the condition of local immunity by determining the urine content of secretory immunoglobulin A (SIgA) under conditions of combined treatment with making use of phlogenzyme, a drug of II-generation systemic enzymotherapy (SE). Recordable in this patients population was a marked increase in the urine level of SIgA. Incorporation in a combined treatment of phlogenzyme results in normalizing the status of the urinary system local immunity. Evidence has been obtained on the lack of parallelism in the dynamics between the serum IgA content and urine concentration of SIgA, which fact suggests independence of local immunity. Our theory is that an appreciable increase in the urine level of SIgA in patients with urolithiasis concurrent with pyelonephritis may have an important part to play in the genesis of nephrolithiasis.

[The combined therapy of patients with chronic nonspecific pyelonephritis using interference currents and and radon procedures]. / Kompleksnaia terapiia bol'nykh khronicheskim nespetsificheskim pielonefritom interferentsionnymi tokami i radonovymi protsedurami.

The exposure of the lumbar region to interference currents in combination with radon baths conducted in 37 patients with chronic pyelonephritis inhibited activity of the inflammation, hypercalciuria and hyperoxaluria, improved function of the kidneys. The same clinical effects were achieved in 32 patients who had received interference therapy in combination with intake of radon water.

[The use of interference currents and iodobromine baths in the therapy of patients with chronic nonobstructive pyelonephritis]. / Primenenie interferentsionnykh tokov i iodobromnykh vann v terapii bol'nykh khronicheskim neobstruktivnym pielonefritom.

30 patients were exposed to interference currents (IC) alone (group 1) versus 34 patients treated with IC plus iodobromine baths (group 2). After IC action on the region of the kidney projection patients of group 1 experienced positive changes in cellular and humoral immunity providing an antiinflammatory effect. In group 2, the improvement was seen in renal and urinary functions, 24-h urinary excretion of oxalates and calcium diminished. Interference current proved beneficial in chronic pyelonephritis patients with latent inflammation. The combined therapy was effective in patients at high risk of lithogenesis.

[Physical factors in the therapy of secondary chronic pyelonephritis]. / Fizicheskie faktory v terapii vtorichnykh khronicheskikh pielonefritov.

The authors have developed combined therapy of secondary chronic pyelonephritis with immune and urodynamic dysfunctions. The treatment includes physical factors: decimeter microwaves, gangleron-electrophoresis with sinusoidal modulated currents, sodium chloride baths, oral mineral water Moskovskaia. The adjuvant use of the above physical factors proved advantageous.