Humanized mouse as an appropriate model for accelerated global HIV research and vaccine development: current trend.

Humanized mouse models currently have seen improved development and have received wide applications. Its usefulness is observed in cell and tissue transplant involving basic and applied human disease research. In this article, the development of a new generation of humanized mice was discussed as well as their relevant application in HIV disease. Furthermore, current techniques employed to overcome the initial limitations of mouse model were reviewed. Highly immunodeficient mice which support cell and tissue differentiation and do not reject xenografts are indispensable for generating additional appropriate models useful in disease study, this phenomenom deserves emphases, scientific highlight and a definitive research focus. Since the early 2000s, a series of immunodeficient mice appropriate for generating humanized mice has been successively developed by introducing the IL-2Rγnull gene (e.g. NOD/SCID/γcnull and Rag2nullγcnull mice) through various genomic approaches. These mice were generated by genetically introducing human cytokine genes into NOD/SCID/γcnull and Rag2nullγcnull mouse backgrounds. The application of these techniques serves as a quick and appropriate mechanistic model for basic and therapeutic investigations of known and emerging infections.

In vitro antioxidant capacity and free radical scavenging evaluation of active metabolite constituents of Newbouldia laevis ethanolic leaf extract.

BACKGROUND: The aim of the present study was to evaluate the in vitro antioxidant and free radical scavenging capacity of bioactive metabolites present in Newbouldia laevis leaf extract. RESULTS: Chromatographic and spectrophotometric methods were used in the study and modified where necessary in the study. Bioactivity of the extract was determined at 10 µg/ml, 50 µg/ml, 100 µg/ml, 200 µg/ml and 400 µg/ml concentrations expressed in % inhibition. The yield of the ethanolic leaf extract of N.laevis was 30.3 g (9.93%). Evaluation of bioactive metabolic constituents gave high levels of ascorbic acid (515.53 ± 12 IU/100 g [25.7 mg/100 g]), vitamin E (26.46 ± 1.08 IU/100 g), saponins (6.2 ± 0.10), alkaloids (2.20 ± 0.03), cardiac glycosides(1.48 ± 0.22), amino acids and steroids (8.01 ± 0.04) measured in mg/100 g dry weight; moderate levels of vitamin A (188.28 ± 6.19 IU/100 g), tannins (0.09 ± 0.30), terpenoids (3.42 ± 0.67); low level of flavonoids (1.01 ± 0.34 mg/100 g) and absence of cyanogenic glycosides, carboxylic acids and aldehydes/ketones. The extracts percentage inhibition of DPPH, hydroxyl radical (OH.), superoxide anion (O2 .-), iron chelating, nitric oxide radical (NO), peroxynitrite (ONOO-), singlet oxygen (1O2), hypochlorous acid (HOCl), lipid peroxidation (LPO) and FRAP showed a concentration-dependent antioxidant activity with no significant difference with the controls. Though, IC50 of the extract showed significant difference only in singlet oxygen (1O2) and iron chelating activity when compared with the controls. CONCLUSIONS: The extract is a potential source of antioxidants/free radical scavengers having important metabolites which maybe linked to its ethno-medicinal use.

In vitro antioxidant capacity and free radical scavenging evaluation of active metabolite constituents of Newbouldia laevis ethanolic leaf extract

BACKGROUND: The aim of the present study was to evaluate the in vitro antioxidant and free radical scavenging capacity of bioactive metabolites present in Newbouldia laevis leaf extract. RESULTS: Chromatographic and spectrophotometric methods were used in the study and modified where necessary in the study. Bioactivity of the extract was determined at 10 µg/ml, 50 µg/ml, 100 µg/ml, 200 µg/ml and 400 µg/ml concentrations expressed in % inhibition. The yield of the ethanolic leaf extract of N.laevis was 30.3 g (9.93%). Evaluation of bioactive metabolic constituents gave high levels of ascorbic acid (515.53 ± 12 IU/100 g [25.7 mg/100 g]), vitamin E (26.46 ± 1.08 IU/100 g), saponins (6.2 ± 0.10), alkaloids (2.20 ± 0.03), cardiac glycosides(1.48 ± 0.22), amino acids and steroids (8.01 ± 0.04) measured in mg/100 g dry weight; moderate levels of vitamin A (188.28 ± 6.19 IU/100 g), tannins (0.09 ± 0.30), terpenoids (3.42 ± 0.67); low level of flavonoids (1.01 ± 0.34 mg/100 g) and absence of cyanogenic glycosides, carboxylic acids and aldehydes/ketones. The extracts percentage inhibition of DPPH, hydroxyl radical (OH.), superoxide anion (O2 .-), iron chelating, nitric oxide radical (NO), peroxynitrite (ONOO-), singlet oxygen (1O2), hypochlorous acid (HOCl), lipid peroxidation (LPO) and FRAP showed a concentration-dependent antioxidant activity with no significant difference with the controls. Though, IC50 of the extract showed significant difference only in singlet oxygen (1O2) and iron chelating activity when compared with the controls. CONCLUSIONS: The extract is a potential source of antioxidants/free radical scavengers having important metabolites which maybe linked to its ethno-medicinal use.

Increased oxygen consumption observed in phorbol 12-myristate 13-acetate stimulated human cultured promonocytic U937 cell lines treated with calcitriol and retinoic acid.

OBJECTIVE: To investigate the effect of phorbol 12-myristate 13-acetate (PMA) and formyl-methionyl-leucyl-phenylalanine (FMLP) on oxygen consumption of differentiated and non-differentiated immune cell lines by retinoic acid and calcitriol treatment which might be useful in subsequent elicitation of immunological action during immunosuppressive states. METHODS: PMA and FMLP were used to artificially stimulate reactive oxygen production in cultured promonocytic U937 cell line. Paralleled samples of the cultured cells were separately prepared with calcitriol (1, 25- dihydroxyvitamin D3) and retinoic acid followed by a 72-hour incubation period. The rate of respiratory burst was measured using the Clark oxygen electrode. RESULTS: The average increase in cell concentrations per mL observed was significantly higher in retinoic acid-treated cells (9×10(6) cells/mL) when compared with calcitriol-treated samples (4×10(6) cells/mL). There was a marked increase in oxygen consumption of the calcitriol-treated cell lines against the retinoic acid-treated ones. Exposure of differentiated U937 cells to PMA and FMLP increased significantly (P<0.05) in their oxygen consumption when compared with the control. PMA calcitriol-treated cells resulted in 55% oxygen consumption more than the control while FMLP oxygen consumption increased 78% by comparison with the control. CONCLUSIONS: The result demonstrated that calcitriol may serve as a physiological promoter of normal differentiation of precursor cells which may exert an immunological action. This effect could elicit a marker potential and increase immune cell activity of the host especially in immunosuppressed diseased states.

Increased oxidative stress condition found in different stages of HIV disease in patients undergoing antiretroviral therapy in Umuahia (Nigeria).

CONTEXT: Effective diagnostic tools for management of HIV disease progression in Sub-Saharan Africa is inadequate considering the endemic nature of the infection in the region. OBJECTIVE: To elucidate the clinical implication of oxidative stress (measured as Malondialdehyde, MDA) as additional biomarker of HIV disease progression and its implication in HIV clinical management. MATERIALS AND METHODS: A total of 250 individuals were recruited for the study. FACScan cytometry and spectrophotometric methods were employed in assessing T-lymphocytes (CD3, CD4, CD8) and MDA respectively. RESULTS: MDA concentration increased significantly (P < 0.05) in highly active antiretroviral therapy (HAART) subjects by 12.72% in category 1, 9.75% in III and in category II (4.63%) on comparison with non-HAART subjects. In subjects taking HAART, 22.2%, 56.3%, and 22.2% were found to be in category I, II and III, respectively, with a corresponding non-HAART values of 15.6%, 45.6% and 38.9%. However, Spearman's rank correlation (P < 0.001) statistics of MDA and HIV categories showed a negative correlation in all the categories (I, II and III). DISCUSSION AND CONCLUSION: These findings suggest that MDA may be an additional clinical factor in assessing progression of HIV disease; however, necessary fortification of regimen with antioxidant may help reduce the high MDA concentration in the disease progression of the infection.