THE STUDY OF THE IMMUNE CORRECTIVE PROPERTIES OF GREEK WALNUT (JUGLANS REGIA L.) SEPTA ON THE EXPERIMENTAL MODEL OF LEUKOPENIA.

From the positive effects of the drugs prepared from various parts of walnut described for a wide variety of diseases, their antitumor effect is remarkable. This feature can be used for treatment of leukopenia caused by radiotherapy and/or chemotherapy. Therefore, to study the immunocorrective properties of Greek walnut, the walnut septa were selected, aqueous extract of which has been studied on experimental model of leukopenia in white mice caused by a single injection of cyclophosphamide. The material of the study were the blood and bone marrow smears from intact and tested adult mice stained by Giemsa's dye. The quantity of leukocytes in peripheral blood were determined by the counting chamber under the light microscope with standard protocol. Cloud-point extraction, HPLC analysis and UV-visible spectrophotometry were used to study the composition of the walnut septa extract. It has been established that the Greek walnut septa extract has the correction ability of suppressed myelopoiesis in white mice caused by injection of cyclophosphamide. The blood formula normalization process by the mentioned extract is provided by the fast increasing in number of immature (band neutrophil) and mature neutrophils in the peripheral blood. It was shown that walnut septa extract stimulates the division, differentiation and maturation of blast forms of myeloid as well as lymphoid line in the bone marrow of mice with leukopenia. Cloud-point extraction and liquid-chromatographic analysis revealed the presence of hydrophilic and hydrophobic components in the walnuts septum extract.

Effect of recombinant Ganoderma lucidum immunoregulatory protein on cyclophosphamide-induced leukopenia in mice.

The aim of the study is to investigate the effect of recombinant Ganoderma lucidum immunoregulatory protein (rLZ-8) on mouse models of cyclophosphamide-induced leukopenia, which we have established with both single-phase and multi-phase administration methods. Treatment with rLZ-8 had a strong effect on both models of cyclophosphamide-induced leukopenia. In particular, it increased the number of neutrophils, lymphocytes and monocytes. rLZ-8 treatment also increased the percentage of CD4(+) T cells and the levels of secreted IL-3 and IL-4, which contributed to the cyclophosphamide-induced immune dysfunction and immune system imbalance. In conclusion, rLZ-8 treatment benefitted mice with cyclophosphamide-induced leukopenia by improving overall immune function and by specifically increasing the number of white blood cells.

Ka-mi-kae-kyuk-tang oriental herbal cocktail attenuates cyclophosphamide-induced leukopenia side effects in mouse.

Ka-mi-kae-kyuk-tang (KMKKT) is an Oriental herbal medicinal cocktail and has been shown to have potent antiangiogenic, anticancer, and antimetastatic activities in preclinical animal models without observable side effects. We previously found that in prostate cancer xenograft experiments, treating tumor-bearing mice with KMKKT alleviated the body weight loss toward the end of the study, suggesting a general health-promoting activity. We investigated whether KMKKT alleviated cancer chemotherapy drug-induced leukopenia and other hematotoxicity in vivo using a mouse model. KMKKT was given once daily orally for 10 days to the mice before they were given cyclophosphamide (CPA) daily injection for 4 days. KMKKT blunted CPA-induced decrease in red blood cells, hemoglobin content, and the total white blood cell/leukocyte counts. Examination of the multiple organ sites involved in hematopoiesis, and lymphocyte differentiation and maturation showed the attenuated changes induced by CPA in each and every type of cells examined. Particularly, some of the cell types are fully restored in the bone marrow and even overstimulated in the Sca-1(+), CD117(+), or Sca1(+)/CD117(+) and CD34(+)/CD117(+) stem cells, supporting a role of KMKKT to stimulate hematopoietic stem cell (HSC) signaling to compensate for CPA-induced destruction of leukocytes and other cell types. Taken together, KMKKT might be a safe and effective herbal complementary and alternative medicine (CAM) modality to alleviate cancer drug-induced hematological side effects in addition to its anticancer activities. Preclinical investigations with other chemo- and radiation modalities are warranted to support planning translation consideration for human patients.

[Clinical study on acupuncture for leukopenia induced by chemotherapy].

OBJECTIVE: To explore the adjunctive therapeutic effects of acupuncture for leukopenia induced by chemotherapy. METHODS Eighty six cases with leukopenia after chemotherapy treatment were randomly divided into a granulocyte colony-stimulating factor (G-CSF) plus acupuncture (A) group and a G-CSF group, 43 cases in each group. After chemotherapy treatments, the patients of both groups were treated with G-CSF for 4 times, with acupuncture at Zhigou (TE 6), Quchi (LI 11), Hegu (LI 4), etc. added in the G-CSF plus A group, for an observaion cycle of 45 days. Their therapeutic effects on the 10th and 31st day and peripheral white blood cell (WBC) counts and neutrophilic granulocyte classification on the 10th, 17th, 24th, 45th day after treatment were compared. RESULTS: After they were treated on the 10th day, the effective rates were both 100.0% (both 43/43), and on the 31st day, the effective rate of 98.9% (42/43) in the G-CSF plus A group was higher than 91.1% (35/43) in the G-CSF group (P < 0.05). The WBC counts in the G-CSF plus acupuncture group were both higher than those in the G-CSF group on the 10th, 17th and 24th day after treatment (all P < 0.05). The ratios of mature neutrophilic granulocyte in the G-CSF plus A group were all higher than those in the G-CSF group at the same time (all P < 0.01). CONCLUSION: Acupuncture can increase the therapeutic effect of G-CSF, delay the decrease of WBC after discontinuing G-CSF, promote the neutrophilic granulocyte differentiating forward to mature and it is better for improving leukopenia induced by chemotherapy.

Prompt and successful toxin-targeting treatment of three patients with necrotizing pneumonia due to Staphylococcus aureus strains carrying the Panton-Valentine leukocidin genes.

Three patients with extensive necrotizing pneumonia due to Panton-Valentine leukocidin-positive Staphylococcus aureus strains and with aggravating factors (leukopenia count of less than 3x10(9)/liter in all three cases and hemoptysis in two cases) were successfully treated with toxin-suppressing agents introduced rapidly after hospital admission.

A polyherbal ayurvedic drug--Indukantha Ghritha as an adjuvant to cancer chemotherapy via immunomodulation.

Indukantha Ghritha (IG) is a polyherbal preparation consisting of 17 plant components widely prescribed by ayurvedic physicians for various ailments. Though it is a known ayurvedic drug, no attempt has been made to scientifically validate its mechanism of action. Preliminary studies in our laboratory showed IG to possess considerable immunomodulatory effects with a Th1 type of immune response. In this regard, we attempted to elucidate its role as an adjuvant to cancer chemotherapy. BALB/c mice were administered IG, for a period of 14 days and parameters such as Hb, total and differential WBC count, bone marrow cellularity, lymphocyte proliferation and function, macrophage phagocytosis and tumor remission were studied. Administration of IG could inhibit tumor development in mice challenged with Dalton's lymphoma ascites. IG-induced leukopoiesis and enhanced median survival time as well as life span in tumor bearing animals. Macrophage phagocytic capacity was also elevated. Flow cytometric analysis of lymphocyte subsets and MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-tetrazolium salt] assay for lymphocyte proliferation, yielded promising results which reinforces its use as an adjuvant to cancer chemotherapy. The polyherbal drug could reverse cyclophosphamide-induced myelosuppression in control tumor bearing animals significantly to values near or above normal levels. These results demonstrate the potential of IG, especially in several immunosuppressed conditions and patients suffering from leukopenia as a consequence of cancer chemotherapy.

Immuno-enhancement effects of Huang Qi Liu Yi Tang in a murine model of cyclophosphamide-induced leucopenia.

Tonic Chinese prescriptions are widely used in daily foods to improve health in Taiwan. Huang Qi Liu Yi Tang (HQLYT) is one such tonic Chinese prescription. In this study, the immuno-enhancement effects of HQLYT tonic were explored using an in vitro splenocyte proliferation assay and by evaluating improvements in cyclophosphamide-induced leucopenia in a BaLb/c mice model. HQLYT is composed of Radix Astragali, licorice, and jujube, and extracted in boiling water. The contents of glycyrrhizin and formononetin were used as bioactive markers to control the quality of the HQLYT water extract, at 7.26+/-0.04mg/g and 112.07+/-0.08 micro g/g, respectively. In the in vitro assay, HQLYT (12.5 micro g/ml) showed better immuno-enhancing effects than Radix Astragali, licorice, or jujube alone, and enhanced the survival rate of splenocytes by 88%. Moreover, HQLYT significantly enhanced the cytotoxic effects of natural killer cells of splenocytes against YAC-1 cells. The BaLb/c mice were fed HQLYT once a day for 14 days. After oral treatment with HQLYT 400mg/kg body weight (BW), the IL-2 release in BaLb/c mice and the natural killer cell activity of the splenocytes were both enhanced, and the WBC level of cyclophosphamide-induced leucopenic mice was improved by treatment with 400mg HQLYT/kgBW. HQLYT significantly delayed the decline in the WBC level and affected a faster recovery of the WBC level back to a normal status. In summary, HQLYT enhanced immunologic functions in both in vitro and in vivo studies. These results offer scientific evidence to prove the efficacy of this tonic Chinese prescription.

[Experimental research of Shuanghuang Shengbai granule on hematopoietic cells of leucopenia model mice].

OBJECTIVE: To investigate the leukogenic function of Shuanghuang Shengbai (SHSB) granule and the related mechanisms. METHOD: Mouse leukopenic models were induced by radiation. Mice were divided into normal control group, model control group, positive control group-Li kejun tablet group and three different dose (high, middle, low-dose) groups of SHSB granule. The peripheral hemogram, thymus index (TI), spleen index (SI), bone marrow nucleated cell (BMNC) and colony forming unit-spleen (CFU-S) were evaluated. The proliferation of bone marrow cells was determined. The in vitro cultured colony forming unit granulocyte macrophage (CFU-GM) was estimated. The index of CD34+ cell in BMNC were determined by flow cytometry. The ultra-micro structure of bone marrow were observed by electromicroscope. RESULT: (1)SHSB rranule could increase the WBC of model mice; (2)SHSB granule could increase BMNC and promote the proliferation of bone marrow cell; (3)SHSB granule could increase CFU-S, CFU-GM and CD34+ cell index in BMNC of model mice significantly; (4)SHSB Granule could also protect the bone marrow hemotopoietic microenvironment from the harm of radiation; (5)SHSB granule could increase the SI of model mice, indicating the enhancement of immunological function. CONCLUSION: SHSB granule has apparent leukogenic function. The mechanism may be related to enhancing the proliferation of hematopoietic cells and protecting the bone marrow hemotopoietic microenvironment.

Evaluation of adaptogenic activity profile of herbal preparation.

The herbal formulation, AVM is a proprietary formula that consists of extracts of herbs that have been used in Indian traditional medicine to promote physical and mental health, improve defense mechanisms of the body and enhance longevity. AVM (500 and 1000 mg/kg) was tested for its adaptogenic activity by determining antistress, anabolic and immunomodulatory effects. In antistress activity, pretreatment with AVM significantly attenuated the changes in ascorbic acid (from blood and adrenal), cortisol (from plasma and adrenal) and adrenal gland weights induced due to restrain stress (physical immobilization). Its antistress effect at 1000 mg/kg was comparable to that of diazepam (5 mg/kg) treated group. Leucopenia, and anemia induced by cyclophosphamide (CYP) was shown to reduce significantly by AVM. Treatment of AVM + CYP had increased spleen and thymus weights significantly as compared to CYP alone treated group. The anabolic activity was evaluated by weight gain of the levator ani muscle, ventral prostrate gland and seminal vesicles in rats as compared to untreated control.

[Effect of radix Ginseng-faeces Trogopterori combination on pharmacodynamics and effective chemical composition of radix Ginseng].

The experiments have shown that there is incompatibility on anti-stress because the action of Radix Ginseng alone is stronger than that of Radix Ginseng and Faeces Trogopterori combined, but there is little incompatibility on non-specific immune function when both are used. The analysis of chemical composition of Radix Ginseng has indicated that the acquired rate of total saponin from the semifinished products and Rg1 of Radix Ginseng is markedly increased when the two drugs are decocted together. The results suggest that the traditional theory is limited in holding that Radix ginseng and Faeces Trogopterori are incompatible with each other.

Protective mechanism of the immune response to a ribosomal vaccine from Pseudomonas aeruginosa. I. In vivo protection studies in compromised animal models.

Studies of the protective activity of a ribosomal vaccine from Pseudomonas aeruginosa in various immunocompromised animal models were performed. The results obtained demonstrated that the vaccine was highly effective in complement (C5)-deficient mice, C3-deficient (cobra venom factor-treated) mice, and leukopenic mice in providing protection against lethal infection with P. aeruginosa. Passive immunization with specific antiserum to the ribosomal vaccine was also effective in leukopenic mice. In mice that were both C5-deficient and leukopenic, the vaccine did not protect mice against lethal infection, but did prolong their survival, whereas in C3-deficient, leukopenic mice significantly enhanced protection was observed. These results were interpreted to suggest the involvement of multiple factors in the protective immune response to the vaccine, including the bactericidal and opsonic activities of specific antibody plus complement and the phagocytic activity of polymorphonuclear leukocytes with opsonized bacteria. Compensation for deficiencies in some of these factors can be obtained by enhancement of other factors through active or passive immunization.