Effect of acyclovir on the radiation-induced micronuclei and cell death

Treatment of HeLa cells with 0.1 microM Acyclovir [9-(2-hydroxyethoxymethyl)guanine] (ACV) before exposure to 0, 0.25, 0.5, 1, 2 and 3 Gy of gamma-radiation resulted in a dose-dependent decline in the growth kinetics and cell proliferation indices at 20, 30 and 40 h post-irradiation when compared with the PBS+irradiation group. These results were reflected in the cell survival, which declined in a dose-dependent manner and the surviving fraction of cells was significantly lower in ACV+irradiation group than that of PBS+irradiation group. The effect of ACV+1 Gy irradiation was almost similar to PBS+3 Gy irradiation suggesting an enhancement of the radiation effect by ACV pretreatment. The frequency of micronuclei increased in a dose-dependent manner at all the post-irradiation time periods in both PBS+irradiation and ACV+irradiation group and it was significantly elevated in the latter when compared with the former group. The dose-response for both groups was linear. The surviving fraction of HeLa cells declined with the increasing MN frequency and a close linear quadratic correlation between cell survival and micronuclei-induction was observed.     

Comparative Pharmacokinetic Study of Mangiferin After Oral Administration of Pure Mangiferin and US Patented Polyherbal Formulation to Rats

The US patented polyherbal formulation for the prevention and management of type II diabetes and its vascular complications was used for the present study. The xanthone glycoside mangiferin is one of the major effector constituents in the Salacia species with potential anti-diabetic activity. The pharmacokinetic differences of mangiferin following oral administration of pure mangiferin and polyherbal formulation containing Salacia species were studied with approximately the same dose 30 mg/kg mangiferin and its distribution among the major tissue in Wistar rats. Plasma samples were collected at different time points (15, 30, 60, 120, 180, 240, 360, 480, 600, 1,440, 2,160, and 2880 min) and subsequently analyzed using a validated simple and rapid LC-MS method. Plasma concentration versus time profiles were explored by non-compartmental analysis. Mangiferin plasma exposure was significantly increased when administered from formulation compared to the standard mangiferin. Mangiferin resided significantly longer in the body (last mean residence time (MRT_last)) when given in the form of the formulation (3.65 h). C_max values of formulation (44.16 μg/mL) administration were elevated when compared to equivalent dose of the pure mangiferin (15.23 μg/mL). Tissue distribution study of mangiferin from polyherbal formulation was also studied. In conclusion, the exposure of mangiferin is enhanced after formulation and administration and could result in superior efficacy of polyherbal formulation when compared to an equivalent dose of mangiferin. The results indicate that the reason which delays the elimination of mangiferin and enhances its bioavailability might the interactions of the some other constituents present in the polyherbal formulation. Distribution study results indicate that mangiferin was extensively bound to the various tissues like the small intestine, heart, kidney, spleen, and liver except brain tissue.

Electronic supplementary material

The online version of this article (doi:10.1208/s12249-014-0206-8) contains supplementary material, which is available to authorized users.KEY WORDS: bioavailability, mangiferin, pharmacokinetics, polyherbal formulation, tissue distribution     

Implementing a mathematical model to compare oxygen uptake kinetics between cyclists and noncyclists during steady state

The purpose was to compare a mathematical model of oxygen uptake and bioenergetic systems to an experimental protocol. Twelve (N = 12) noncyclists (NC), age (21.8 ± 1.4 years), and 8 (N = 8) cyclists (C), age (30.5 ± 5.7 years), were subjects. All subjects signed an informed consent. Oxygen consumption (VO2, ml·kg?1·min?1) was measured with steady-state VO2 requirements and responses determined using the mathematical model from the following equation: VO2 (WR) = VO2 (rest) + VO2 (unloading pedaling) + α.WR; ΔVO2(t, WR) = ΔVO2 (WR) = [1-e[-(t-td)/tO2]. Exercise means (SD) included the following: VO2NC(WR) = 48.4 (16.6) ml?1·min?1 for NCs and VO2C(WR) = 56.4 (24.95) ml?1·min?1 for Cs ; ΔVO2C(t, WR) = 6:38 ml?1·min?1 for NCs and ΔVO2C(t, WR) = 7.44 ml?1·min?1 for Cs. The correlation between the mathematical model and actual measure was statistically significant (p < 0.01) with a coefficient of r = 0.947. The experimental protocol was significantly associated with the mathematical model. This allows for a quantitative analysis and safe prediction of steady-state oxygen uptake conditions on populations before exposure to exercising conditions. Through more precise analysis of conditions, greater specificity of training may lead to more predictable adaptation outcomes.     

Fruit fly parasitoids in coffee in Mpumalanga Province,South Africa

Bracon celer, Psyttalia perproxima, Psyttalia humilis (all Hymenoptera: Braconidae) and Tetrastichus giffardianus (Hymenoptera: Eulophidae) were reared from fruit flies (Diptera: Tephritidae) infesting Coffea canephora in Mpumalanga, South Africa. Psyttalia perproxima and T. giffardianus were recorded for the first time from southern Africa. Ceratitis capitata was likely the main tephritid host.     

Procathepsin D expression correlates with invasive and metastatic phenotype of MDA-MB-231 derived cell lines

Procathepsin D (pCD) is a glycoprotein secreted abundantly by cancerous cells with a documented role in tumor development. The levels of pCD in primary tumors are highly correlated with an increased incidence of metastasis. Our earlier studies have shown that pCD exerts its effect on cancer cells through its activation peptide (AP) and involves both autocrine and paracrine modes of action. In this study, we analyzed the expression and role of pCD in MDA-MB-231 and its derived cell lines 1833 and 4175 possessing discrete metastatic abilities. Our results demonstrated a direct relationship between expression and secretion of pCD to the differential invasive potential of these cells. Also, the cell lines responded to AP treatment by enhancing their invasive potential, proliferation and induction of secretion of various cytokines, suggesting that pCD plays a role in metastasis through its AP region.     

Development of photochemical method for meniscal repair: a preliminary study

Visible light combined with naphthalimides has previously been shown to catalyze formation of physical bonds in avascular meniscal tissue. The first objective was to modify the existing in vitro testing method (i.e., adhesion testing using lap-jointed slices) to gain more sensitivity in detecting relative bonding strengths among candidate bonding agents. A repeated measures experimental design (RMED) was used to account for variability in properties among bovine menisci and was achieved by testing all treatments/controls on slices from each meniscus. Additionally, to make the method more clinically relevant in modeling a bucket-handle tear, the bovine meniscal slices were cut with collagen fibers parallel to the test slice's length. Peak stress was greater for the complete treatment group (light plus naphthalimide) than for the control or incomplete treatment groups (light only or napthalimide only). The second objective was to perform concentration and photoactivation time dose-response studies. In the concentration dose-response study, peak stress was greater for all treatments when compared with the control but not different among treatment groups; however, there was a trend of increased bonding strength with increased concentration. In the photoactivation time dose-response study, peak stress was greater for all treatments when compared with the control and greater for the 3-min treatment vs. the 6- and 9-min treatments. Peak stress was not different between the longer treatments. The RMED provided increased reproducibility and statistical sensitivity for detecting differences among treatments and will be used to test candidate bonding agents prior to in vivo testing.     

Novel pathways that contribute to the anti-proliferative and chemopreventive activities of calcitriol in prostate cancer

Calcitriol, the hormonally active form of Vitamin D, inhibits the growth and development of many cancers through multiple mechanisms. Our recent research supports the contributory role of several new and diverse pathways that add to the mechanisms already established as playing a role in the actions of calcitriol to inhibit the development and progression of prostate cancer (PCa). Calcitriol increases the expression of insulin-like growth factor binding protein-3 (IGFBP-3), which plays a critical role in the inhibition of PCa cell growth by increasing the expression of the cell cycle inhibitor p21. Calcitriol inhibits the prostaglandin (PG) pathway by three actions: (i) the inhibition of the expression of cyclooxygenase-2 (COX-2), the enzyme that synthesizes PGs, (ii) the induction of the expression of 15-prostaglandin dehydrogenase (15-PGDH), the enzyme that inactivates PGs and (iii) decreasing the expression of EP and FP PG receptors that are essential for PG signaling. Since PGs have been shown to promote carcinogenesis and progression of multiple cancers, the inhibition of the PG pathway may add to the ability of calcitriol to prevent and inhibit PCa development and growth. The combination of calcitriol and non-steroidal anti-inflammatory drugs (NSAIDs) result in a synergistic inhibition of PCa cell growth and offers a potential therapeutic strategy. Mitogen activated protein kinase phosphatase 5 (MKP5) is a member of a family of phosphatases that are negative regulators of MAP kinases. Calcitriol induces MKP5 expression in prostate cells leading to the selective dephosphorylation and inactivation of the stress-activated kinase p38. Since p38 activation is pro-carcinogenic and is a mediator of inflammation, this calcitriol action, especially coupled with the inhibition of the PG pathway, contributes to the chemopreventive activity of calcitriol in PCa. Mullerian Inhibiting Substance (MIS) has been evaluated for its inhibitory effects in cancers of the reproductive tissues and is in development as an anti-cancer drug. Calcitriol induces MIS expression in prostate cells revealing yet another mechanism contributing to the anti-cancer activity of calcitriol in PCa. Thus, we conclude that calcitriol regulates myriad pathways that contribute to the potential chemopreventive and therapeutic utility of calcitriol in PCa.