Curcumin-artemisinin combination therapy for malaria

Artemisinin and curcumin show an additive interaction in killing Plasmodium falciparum in culture. In vivo, 3 oral doses of curcumin following a single injection of alpha,beta-arteether to Plasmodium berghei-infected mice are able to prevent recrudescence due to alpha,beta-arteether monotherapy and ensure almost 100% survival of the animals.     

Effect of lipopolysaccharide on alteration of phospholipids and their fatty acid composition in spleen and thymus by in vitro metabolic labeling

Lipopolysaccharide (LPS) is an endotoxin, a potent stimulator of immune response and induction of LPS leads to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). ARDS is a life‐threatening disease worldwide with a high mortality rate. The immunological effect of LPS with spleen and thymus is well documented; however the impact on membrane phospholipid during endotoxemia has not yet been studied. Hence we aimed to investigate the influence of LPS on spleen and thymus phospholipid and fatty acid composition by [³²P]orthophosphate labeling in rats. The in vitro labeling was carried out with phosphate‐free medium (saline). Time course, LPS concentration‐dependent, pre‐ and post‐labeling with LPS and fatty acid analysis of phospholipid were performed. Labeling studies showed that 50 µg LPS specifically altered the major phospholipids, phosphatidylcholine and phosphatidylglycerol in spleen and phosphatidylcholine in thymus. Fatty acid analysis showed a marked alteration of unsaturated fatty acids/saturated fatty acids in spleen and thymus leading to immune impairment via the fatty acid remodeling pathway. Our present in vitro lipid metabolic labeling study could open up new vistas for exploring LPS‐induced immune impairment in spleen and thymus, as well as the underlying mechanism. Copyright © 2011 John Wiley & Sons, Ltd.     

Effect of restraint stress duration on humoral immune response in albino rats: modulation by chlordiazepoxide

We evaluated the effect of restraint stress (1 hr/day) for 6, 10, 14 and 21 days on antibody response against sheep RBC (SRBC) and modulation by chlordiazepoxide (CDP) pretreatment (10 mg/kg/day) in albino rats. Anti-SRBC titer was significantly decreased with increase in number of days of restraint stress exposure. CDP pretreatment significantly reversed the effects of 6, 10 and 14 (but not of 21) days of restraint stress. CDP treatment for 21 days per se suppressed immune response, but no additive effect was observed. CDP was not effective in chronic stress (i.e., 21 days of stress). Hence, the rationale behind benzodiazepines therapy in chronic stress needs to be evaluated.     

Anomalous behavior of pentacoordinate copper complexes of dimethylphenanthroline and derivatives of terpyridine ligands: Studies on DNA binding, cleavage and apoptotic activity

Copper(II) complexes with substituted terpyridine ligands, namely [Cu(itpy)(dmp)](NO₃)₂ (1) and [Cu(ptpy)(dmp)](NO₃)₂ (2) have been synthesized and characterized. The interaction of the complexes with CT-DNA has been explored using spectroscopic techniques and viscosity. Complexes 1 and 2 bind in the grooves of DNA, interestingly 1 in the minor and 2 in the major groove. Both the complexes have been found to promote DNA cleavage; complex 1 through hydrolytic and 2 oxidative. Complexes 1 and 2 have been found to be cytotoxic and bring about apoptosis of human lung cancer cell line A549.     

Pregnancy-exaggerated galactosemia and congenital cataracts

One child In a family and two children in another family had galactosemia and congenital cataract. Two of them had total soft cataracts while in one, cataract was less soft. In addition, they had mild lactosuria. The mothers of the affected children had significant lactosuria and mild galactosuria without cataracts. Fathers did not have galactosuria or lactosuria. Clinically unaffected siblings in one family had mild galactosuria and lactosuria. Pregnancy-exaggerated galactosemia was suspected in these two mothers who gave birth to children with congenital cataract. As an extension of this work, 5001 pregnant women were screened for galactose in urine just before the delivery of babies. Mild galactosuria was present in 54 (1.08%). Three children had congenital cataract and one had changes in posterior pole and cornea. Restriction of lactose by reducing intake of milk and milk products during pregnancy by mothers with galactosuria is recommended to avoid the birth of children with congenital cataract.     

A comparative study of electronic cigarette vapor extracts on airway-related cell lines in vitro

The use of electronic cigarettes (ECs) is rapidly increasing worldwide; however, scientific evidence regarding EC cytotoxicity is limited. The aim of this study was to evaluate the acute cytotoxicity of EC vapor extract (ECE) on airway-related cells in vitro. Cigarette smoke extract (CSE), vapor extract of fifteen brands/flavors of ECs and the extract from the E-vehicle (propylene glycol and glycerin) was collected. Extracts, in concentrations of 100–12.5%, were added to human bronchial epithelial (BEAS-2B, IB3-1 and C38), fibroblast (Wi-38) and macrophage (J774 and THP-1) cell lines. Viability was assessed after 24?h using a standard XTT assay. Viability of <70% of control (no extract) was considered cytotoxic according to UNI EN ISO 10993-5 standards. CSE displayed a concentration-dependent influence on cell viability across all four cell lines with 100% producing the most toxic effect, therefore validating the model and indicating higher cytotoxicity than in ECEs. ECEs did reduce viability although this was not correlated with nicotine content or the E-vehicle. However, several flavors proved cytotoxic, with variation between different brands and cell lines. These data indicate that not all ECs are the same and that use of a particular flavor or brand may have differing effects. The cell line used is also an important factor. More research is crucial to ascertain the health effects of different ECs before they can be accepted as a safe alternative to tobacco cigarettes.     

Integrin α3β1 can promote adhesion and spreading of metastatic breast carcinoma cells on the lymph node stroma

We have reported that metastatic human melanoma cells utilize the α_vβ₃ integrin to adhere to lymph node vitronectin (VN). In the present study, the adhesion of human and rat breast carcinoma cells to lymph node tissue was analyzed. We have previously shown a correlation between the metastatic potential of breast carcinoma cells and an RGD-mediated adhesion to cryostat sections of peripheral lymph nodes; this adhesion could be blocked by an antibody to the integrin β₁ subunit. Here, we show that the metastatic breast carcinoma cell were significantly more adherent to fibronectin (FN) expressed by lymph node-derived stromal cells than non-metastatic cells. Metastatic cells also spread more rapidly than non-metastatic cells on FN-coated substrates. Using a combination of immunofluorescence microscopy, immunoprecipitation and blocking assays with integrin-specific antibodies, we found (i) that expression of the α₃β₁ integrin on metastatic mammary carcinoma cells was specifically increased in comparison to non-metastatic cells and (ii) that the α₃β₁ receptor was involved in the increased adhesion of metastatic cells to lymph node FN and in cell spreading on FN-coated substrates. Our data also suggest that the α₅β₁ integrin, which is also expressed on the metastatic cells, did not contribute to this increase in adhesion. Our data implicate the α₃β₁ integrin in adhesion to lymph node stromal cell FN and suggest that metastatic cells of different tissue origins (e.g., melanoma and breast carcinoma) may utilize distinct integrin-ligand combinations to colonize the same target organ. © 1996 Wiley-Liss, Inc.     

Effect of Restraint Stress Duration on Humoral Immune Response in Albino Rats: Modulation by Chlordiazepoxide

We evaluated the effect of restraint stress (1hr/day) for 6, 10, 14 and 21 days on antibody response against sheep RBC (SRBC) and modulation by chlordiazepoxide (CDP) pretreatment (10 mg/kg/day) in albino rats. Anti-SRBC titer was significantly decreased with increase in number of days of restraint stress exposure. CDP pretreatment significantly reversed the effects of 6, 10 and 14 (but not of 21) days of restraint stress. CDP treatment for 21 days per se suppressed immune response, but no additive effect was observed. CDP was not effective in chronic stress (i.e., 21 days of stress). Hence, the rationale behind benzodiazepines therapy in chronic stress needs to be evaluated.