Regioselective synthesis of some new dispiro[indane-2,3'-pyrrolidine-2',3"-indoline]-1,2",3- triones (4a-j) has been generated by 1,3-dipolar cycloaddition reaction of 2-arylidene-indan-1,3- diones (1a-j) as dipolarophiles with non-stabilized azomethine ylides, generated in situ via decarboxylative condensation of isatin (2) and sarcosine (3). Anti-inflammatory activity of the prepared compounds (4a-j) was determined in vivo by the acute carrageenan-induced paw edema in rats. Many of the prepared compounds exhibit considerable anti-inflammatory properties "at a dose of 10 mg/kg body weight", especially (4b) and (4c) which reveal promising activities relative to indomethacin which was used as a reference standard in this study.

Regioselective synthesis of some new dispiro[indane-2,3'-pyrrolidine-2',3"-indoline]-1,2",3- triones (4a-j) has been generated by 1,3-dipolar cycloaddition reaction of 2-arylidene-indan-1,3- diones (1a-j) as dipolarophiles with non-stabilized azomethine ylides, generated in situ via decarboxylative condensation of isatin (2) and sarcosine (3). Anti-inflammatory activity of the prepared compounds (4a-j) was determined in vivo by the acute carrageenan-induced paw edema in rats. Many of the prepared compounds exhibit considerable anti-inflammatory properties "at a dose of 10 mg/kg body weight", especially (4b) and (4c) which reveal promising activities relative to indomethacin which was used as a reference standard in this study.

Whey protein concentrates (WPCs) enhance innate mucosal immunity during early life and have a protective role in some immune disorders. To further elucidate the potential benefits of this protein, the present study investigated the effect of dietary supplementation with WPCs on blood parameters, plasma cytokine profiles, and immune cell proliferation and chemotaxis. A total of 45 male mice were equally distributed into three experimental groups and treated daily for 21 days as follows: group I was a control group that was orally supplemented with distilled water, group II was orally supplemented with undenatured WP (100 mg/kg body weight), and group III was orally supplemented with bovine serum albumin (100 mg/kg body weight). We found that the plasma cytokine levels of interleukin (IL)-1α, IL-1β, IL-10 and tumor necrosis factor-α and the levels of reactive oxygen species, cholesterol, triglycerides and the lipid profile were significantly decreased in the WP-treated group compared to the control group. In contrast, the levels of IL-2, IL-4, IL-7, IL-8 and glutathione were significantly elevated, and consequently, the ability of peripheral blood mononuclear cells to proliferate in response to stimulation with different antigens was significantly increased in the WP-treated group. Moreover, the in vitro chemotaxis of B, T and bone-marrow-derived dendritic cells toward CC chemokine ligand- 21 and CXC chemokine ligand-12 was significantly increased, by twofold, in WP-treated mice compared to the control group. Taken together, our data reveal the benefits of WP supplementation in enhancing immune cell proliferation and migration to the secondary lymphoid organs. © 2012 Elsevier Inc. All rights reserved.

Long and persistent uncontrolled diabetes tends to degenerate the immune system and increase the incidence of infections in diabetic patients. A serious complication of diabetes is impaired healing, which diminishes physical activity and, in some cases, leads to chronic wounds and limb amputation. Whey proteins (WPs) enhance immunity during early development and have a protective role in some immune disorders. The effect of camel WPs on wound healing in a streptozotocin-induced type 1 diabetic mice model was investigated. Sixty male mice were equally distributed into 3 experimental groups: group 1, non-diabetic control mice; group 2, diabetic mice; and group 3, diabetic mice that were orally supplemented with undenatured WP (100 mg/kg body weight/day for 1 month through oral gavage). We observed that the diabetic mice exhibited delayed wound closure characterized by a significant reduction in collagen deposition, prolonged elevation in inflammatory cytokines, aberrant activation of STAT3 and reduction in the activation of Akt and NF-κB when compared with the control mice. Moreover, in the diabetic mice, the wound-resident macrophages were dysfunctional and demonstrated increased apoptosis, a significant reduction in their phagocytotic ability, aberrant activation of STAT3 and a marked reduction in the activation of Akt. Interestingly, the supplementation of diabetic mice with WP significantly enhanced the collagen deposition, limited the inflammatory stimuli, restored the activation of STAT3, Akt and NF- κB and greatly improved the closure of diabetic wounds compared with the control mice. Most important, the supplementation of diabetic mice with WP rescued functional, long-lived wound-resident macrophages. Our data reveal the benefits of WP supplementation in improving the healing and closure of diabetic wounds.

In the present study we evaluated the anti-tumor potential of samsum ant venom (SAV) from Pachycondyla sennaarensis on the human breast carcinoma cell line MCF-7. We found that SAV induced growth arrest of MCF-7 cells without affecting the viability of MCF-10 (non-tumorigenic normal breast epithelial cells) and normal PBMCs. We then analyzed its impact on IGF-1-mediated MCF-7 cell proliferation and its effect on the underlying IGF-1 signaling pathways. Using flow cytometry analysis, we showed that the percentage of apoptotic cells was fourfold higher in SAV-treated cells as compared to untreated cells. More importantly, treatment with SAV induced a marked reduction in actin polymerization and a subsequent marked reduction in IGF-1-mediated cell proliferation. In addition to growth-inhibitory and proapoptotic effects, significant reductions were also observed in the phosphorylation of AKT and ERK, but not p38MAPK, in SAV-treated cells as compared to untreated cells. Our data reveal unique anti-tumor effects of samsum ant venom.

OBJECTIVE: We investigated the impact of maternal food restriction during gestation and lactation on the number and function of peripheral T cells in adult male offspring. STUDY DESIGN: Pregnant rats either received ad libitum (control) feed or were 50% food restricted (FR) from day zero of gestation to delivery and during the lactation period. After weaning, pups from control and FR mother rats were fed normally until they reached 8 weeks of age. At 8 weeks of age, blood parameters, plasma cytokine levels, and T cell number and function were determined in 10 male offspring from each group. RESULTS: FR offspring exhibited decreased numbers of total and CD4+ and CD8+ T lymphocytes and a significant reduction in plasma IL-2 and IL-7 compared with control offspring. In addition, T lymphocytes from FR offspring exhibited a 2-fold decrease in IL-2- and IL-7-mediated AKT and STAT5 phosphorylation, altered actin polymerization, and diminished superantigen-mediated proliferation and cytokine production as compared with control offspring. CONCLUSIONS: aken together, these findings suggest that early undernutrition, particularly during the prenatal and lactation periods, attenuates T cell survival and the immune response.

To investigate T-cell functional molecules and inflammatory cytokines and to assess T-cell apoptosis in malnourished infants, 64 infants from undernourished women and 28 healthy control infants were recruited to the study. Malnourished infants showed a significant decrease in the levels of circulating IL-2 and IL-7 and increases in the levels of IL-1, IL-6, IL-10 and TNF-, as measured by flow cytometry. There was a significant reduction in the number of CD3+ T cells and an increase in apoptotic T cells, which was associated with an up-regulation of CD95 and PD-1 expression on CD3+ T cells in malnourished compared to control infants. Significant reductions were also observed in the phosphorylation of AKT and STAT5 and in the expression of CCR7 and CXCR4 receptors in malnourished children, and these reductions were associated with a significant reduction in T-cell migratory capacity to their ligands CCL21 and CXCL12, respectively, as measured using an in vitro chemotaxis assay. Taken together, these data suggest that lymphocytes from malnourished infants are short-lived and dysfunctional.

Steady natural convection cooling of a localized heat source at the bottom wall of an enclosure filled with Cu-water nanofluid for a variety of thermal boundary conditions at the sidewalls has been studied in the present paper. Finite difference method was employed to solve the dimensionless governing equations of the problem. The effects of governing parameters, namely, solid volume fraction, the different values of the heat source length and the different locations of the heat source on the streamlines and isotherms contours as well as maximum temperature, Nusselt number and average Nusselt number along the heat source were considered. The present results are validated by favorable comparisons with previously published results. The results of the problem are presented in graphical and tabular forms and discussed.

In this paper, a numerical solution of flow and heat transfer in micropolar fluid outside a stretching permeable cylinder with thermal stratification and suction/injection effects. The governing system of partial differential equations is converted to ordinary differential equations by using similarity transformations, which are then solved using numerical technique. The cases of strong concentration of microelement and weak concentration of microelement were considered. Our purpose from this study is to investigate the effects of the governing parameters, namely the suction/injection parameter, thermal stratification parameter, Prandtl number, vortex viscosity parameter and Reynolds number on the velocity profiles, pressure distributions, angular velocity profiles and temperature profiles as well as the skin friction coefficient, dimensionless wall couple stress and the Nusselt number. The numerical results are validated by favorable comparisons with previously published results. The results are shown graphically. The values of the skin friction coefficient, dimensionless wall couple stress and the Nusselt number are presented in tables. Copyright  2011 John Wiley & Sons, Ltd.

This paper presents a numerical investigation of laminar mixed convection cooling of heat source embedded on the bottom wall of an enclosure filled with nanofluids. The transport equations for a Newtonian fluid are solved numerically with a finite volume approach using the SIMPLE algorithm. The influences of governing parameters, namely, Rayleigh number location and geometry of the heat source, the type of nanofluid and solid volume fraction of nanoparticles on the cooling performance is studied. The present results are validated by favourable comparisons with previously published results. The results of the problem are presented in graphical and tabular forms and discussed.