EVALUATION OF THE EFFECTS OF THE HYDRO-ETHANOLIC ROOT EXTRACT OF ZANTHOXYLUM ZANTHOXYLOIDES ON HEMATOLOGICAL PARAMETERS AND OXIDATIVE STRESS IN CYCLOPHOSPAMIDE TREATED RATS.

BACKGROUND: The use of cyclophosphamide in cancer therapy is usually associated with challenging immunosuppression which exposes patients to increased risk of anemia and necessitating preventive measures during therapy. This study was carried out to investigate the efficacy of the hydro-ethanolic extract of the root of Z. zanthoxyloides in preventing and/or improving cyclophosphamide induced myelosuppression and oxidative stress in rats. MATERIALS AND METHODS: Animals were divided into 6 groups of 6 rats each and were pretreated oral doses of 75, 150 and 225 mg/kg of the extract for 7 days and then co-administered with 2.5 mg/kg cyclophosphamide for 28 days. RESULTS: The LD50 of the extract was found to be 1682.3 mg/kg. Phytochemical analysis of the plant extract showed the presence of tannins, saponins, alkaloids and flavonoids, glycosides, terpenoids and phenols. In the anti-oxidant enzyme assay, CAT was significantly (p < 0.05) increased for animals treated with 150 mg/kg+CP compared to 75 mg/kg+CP and 225 mg/kg+CP. GPx was significantly (p < 0.01) increased in rats treated with 75 mg/kg+CP compared to 150 mg/kg+CP and control. SOD was significantly (p < 0.01) increased in rats treated with 75 mg/kg+CP compared to the control. WBC was significantly (p < 0.05) reduced for 225 mg/kg, 225 mg/kg+CP (p < 0.001), 150 mg/kg+CP (p < 0.001), 75 mg/kg+CP (p < 0.001) and CP administered rats (p < 0.001) respectively compared to the control. LDL and CHOL were significantly reduced (p < 0.05) for rats treated with 75 mg/kg+CP, 225 mg/kg+CP and 225 mg/kg. CONCLUSION: Findings from this study demonstrates that the hydro-ethanolic root extract of Z. zanthoxyloides could be beneficial in hyperlipidemia and in cases of malignancies with abnormal cholesterol metabolism an effect which may be mediated via combating oxidative stress. List of Abbreviations: EDTA: Ethylenediamine-tetra acetate; MDA: Malondialdehyde; PCV: Packed cell volume; RBC: Red blood cell; HGB: Hemoglobin; WBC: White blood cell; ALT: Alanine transaminase; AST: Aspartate transaminase; CHOL: Cholesterol; LDL: Low density lipoprotein; HDL: High density lipoprotein; GSH: Reduced glutathione; SOD: Superoxide dismutase; CAT: Catalase; CP: Cyclophosphamide.

Vitamin D deficiency in children with a chronic illness-seasonal and age-related variations in serum 25-hydroxy Vitamin D concentrations.

INTRODUCTION: Children and adolescents with a chronic illness have potential risk factors for vitamin D deficiency. An optimal vitamin D status might have multiple health effects. This study evaluated vitamin D status and its association with age, gender, and season in a large cohort of chronically ill Finnish patients at a tertiary pediatric outpatient clinic. A cross-sectional register-based study was carried out, involving altogether 1351 children (51% boys, age range 0.2-18 years), who visited the outpatient clinic during 2007-2010 and had their vitamin D status (S-25-OHD) determined. A post-doc analysis was conducted to identify predisposing and preventing factors for vitamin D deficiency. RESULTS: Almost half (47%) of the S-25-OHD values were consistent with subnormal vitamin D status (S-25-OHD <50 nmol/L) while only 12% were >80 nmol/L. Age and season were the most important determinants for S-25-OHD concentration. Mean S-25-OHD concentration differed between age groups (Kruskal-Wallis; p<0.001), adolescents being at highest risk for vitamin D insufficiency. Young age and vitamin D supplementation were preventive factors for deficiency, while non-Finnish ethnic background was a predisposing factor. S-25-OHD showed significant seasonal variation in children older than 6 years. In the whole cohort, S-25-OHD was on average 13 nmol/L higher in summer than in winter, and the prevalence of vitamin D deficiency ( =  S-25-OHD <37.5 nmol/l) varied from 11% in summer to 29% in winter. CONCLUSIONS: The finding that almost half of the studied Finnish children with a chronic illness had suboptimal vitamin D status is alarming. Inferior vitamin D status was noted in adolescents compared with younger children, suggesting that imbalance between intake and requirement evolves with age. Although less common during summer, subnormal vitamin D status was still observed in 28% of those evaluated in summer. Clinicians should identify individuals at risk and actively recommend vitamin D supplementation.

Alfacalcidol treatment restores derailed immune-regulation in patients with undifferentiated connective tissue disease.

Vitamin D deficiency may contribute to pathological changes in the number and function of CD4+ T helper cell subsets (CD4+Th1, CD4+Th17, CD4+CD25(bright)Foxp3-natural regulatory T cells-nTreg) in patients with undifferentiated connective tissue disease (UCTD). The aim of the present study was to evaluate, whether alfacalcidol could restore immune-regulatory changes in patients with UCTD. We assessed the optimal dose of alfacalcidol that could normalize the elevated levels of IFN-γ expressed by the CD4+Th1 cells and the IL-17 expressed by Th17 cells. Furthermore alfacalcidol decreased the Th1 and Th17 related cytokine levels, repaired the nTreg/Th7 balance, and restored the functional activity of nTreg cells. Twenty one UCTD patients with Vitamin D deficiency (<30 ng/ml) were administered with three different daily doses of alfacalcidol. Seven patients were supplemented with 0.5 µg/day, 7 patients with 1.0 µg/day, and 7 patients with 1.5 µg/day alfacalcidol treatment during 5 weeks. Our results indicated that 1.0 µg/day alfacalcidol during 5 weeks was the optimal therapeutic regime to increase the vitamin D levels, repair the nTreg/Th17 balance and raise the capacity of nTreg cells to suppress the proliferation of autologous CD4+CD25- cells. 1.5 µg daily dose alfacalcidol was not more effective than the 1.0 µg/day treatment. In this study we described that vitamin D deficiency can contribute to the complex immune-regulatory abnormalities in patients with UCTD and vitamin D substitution therapy can improve the fine balance of pro- and anti-inflammatory processes in the disease.

[High-mountain climate therapy for skin diseases and allergies-- mode of action, therapeutic results, and immunologic effects]. / Hochgebirgsklimatherapie bei Dermatosen und Allergien--Wirkmechanismen, Ergebnisse und Einflüsse auf immunologische Parameter.

Dermatological-allergologic climatotherapy is interpreted as a therapy within a specific climate with proven therapeutic benefits, immediate and longterm. Intensive classical dermatological in-patient therapy is combined with specific climatic effects. Primarily, the climate of the high mountains (1560 m) and of the North Sea islands is of proven efficacy for dermatoses and allergic diseases such as atopic dermatitis (neurodermatitis), eczema, psoriasis, T-cell lymphoma, bronchial asthma. Specialized therapeutic utilities exist. Directly influencing climatic factors such as insolation, thermic-hygric and aerosol conditions without or with diminished allergic potency and nonspecific stimulating climate factors change immune functions and effect stabilization. The therapeutic immediate and longterm efficacy of the high mountain climate is proven by excellent follow-up results. Its superiority to the dermatological therapy applied at home is evident. Measurement and analysis of climate efficacy has however proven difficult because of its complexity. The findings of several recent clinical and biochemical studies are presented.

Zinc and immune function.

Zinc and immune function relationship has been extensively studied. Both in experimentally induced mineral deficit and in genetically determined deficit observable in acrodermatitis enteropathica and in enteropathy of Danish A-46 cattle, a B and T dependent antibody response decrease, a T dependent cytolytic response decrease and a natural killer cytotoxic activity decrease are present noteviously. Serious reduction of the immune function is present, in proportion to the value of low zinc plasmatic level, in elderly patients, in malnourished and seriously zinc deficient children, in patients subjected to total parenteral supply, in HIV infections and especially in evident AIDS: in this condition the plasmatic zinc level can be considered, together with the CD4+ lymphocytes amount and the B2-microglobulin value, a disease progression marker. Zinc immunostimulating action mechanisms are complex, although thymic hormone (of which zinc is essential cofactor) stimulation seems to be most important. Zinc supplementation, also parenterally, can be useful in immunodeficiency (in the elderly, in the post-surgical patients, in genetically determined or alimentary induced deficit, in AIDS.