Ligand Tuning of Localized Surface Plasmon Resonances in Antimony-Doped Tin Oxide Nanocrystals.

Aliovalent-doped metal oxide nanocrystals exhibiting localized surface plasmons (LSPRs) are applied in systems that require reflection/scattering/absorption in infrared and optical transparency in visible. Indium tin oxide (ITO) is currently leading the field, but indium resources are known to be very restricted. Antimony-doped tin oxide (ATO) is a cheap candidate to substitute the ITO, but it exhibits less advantageous electronic properties and limited control of the LSPRs. To date, LSPR tuning in ATO NCs has been achieved electrochemically and by aliovalent doping, with a significant decrease in doping efficiency with an increasing doping level. Here, we synthesize plasmonic ATO nanocrystals (NCs) via a solvothermal route and demonstrate ligand exchange to tune the LSPR energies. Attachment of ligands acting as Lewis acids and bases results in LSPR peak shifts with a doping efficiency overcoming those by aliovalent doping. Thus, this strategy is of potential interest for plasmon implementations, which are of potential interest for infrared upconversion, smart glazing, heat absorbers, or thermal barriers.

DEVELOPMENT OF AN IN VITRO RNAI TO INVESTIGATE GENE FUNCTION IN BRUGIA MALAYI.

The RNA interference (RNAi) has the ability to turn off individual gene expression. So, it affords a remarkably specific tool for studying the effects of genes. It is regarded as a direct approach for determining such gene/genes functions and offers a valuable tool for modern drug discovery. The study aimed to develop in vitro RNAil in Brugia malayi with particular interest to study the function of Brugia malayi avr-14 (Bm-avr-14) and Brugia malayi f-tubulin (Bm-fi-tubulin) genes. Bm-avr-14 is a gene encoding glutamate gated chloride channel (GluCl) which binds ivermectin and Bm-ß-tubulin is a gene encoding ß-tubulin which binds albendazole. Adult female worms were soaked in heterogeneous short interfering RNA (hsiRNA) with interest to study the role of two genes Bm-avr-14 and Bm-ß-tubulin. Then, we assessed the knock down effects of target genes using worminator system and real time PCR. We found that worms treated with hsiRNA of Bm-avr-14 had a significant reduction in microfilariae (mf) production in comparison with untreated worms or worms treated with hsiRNA of green fluorescent protein (GFP). No significant reduction in mf production with Bm-ß-tubulin gene was obtained. There were no changes in the movement of adults treated with either Bm-avr-14 or Bm- ß-tubulin hsiRNAs. Inconsistent RNAi mediated suppression was achieved with Bm-avr-14 and Bm-ß- tubulin using real time PCR. The data may be helpful in assessment of drug target potential of genes.

Transient effects of levamisole on Brugia malayi microfilariae.

Levamisole is an anthelmintic drug that acts by activating nicotinic acetylcholine receptors at the nematode neuromuscular junction and causing paralysis. We measured the in vitro effects of levamisole on the motility of Brugia malayi microfilariae; after 2 h incubation the apparent IC50 was 2.68 mM. Lower drug concentrations, such as 1 mM, caused an immediate total paralysis that lasted for up to 1 h, but was completely reversed by 2 h of incubation. The 'recovered' parasites were still completely susceptible to application of a second nicotinic agonist, pyrantel.

Relationship between serum cytokines profiles and hepatic fibrosis in schistosomiasis mansoni: an experimental study.

Forty of eighty mice (10 each group) were infected with S. mansoni cercariae and sacrificed at 3 weeks (G-A), 6 weeks (G-B), 12 weeks (G-C) and 16 weeks (G-D) post infection (P.I). The other forty mice were used as control groups of ten mice each. There were highly significant difference between egg counts after 12 weeks & 16 weeks of infection compared to 6 weeks P.I. The maximum egg count and mature eggs were in 6th week P.I while dead eggs reached the peak at 16th weeks P.I. Liver egg counts showed maximum followed by intestinal and then, stool egg counts. A highly significant differences in hydroxyproline, TGF-Bland IL-4 of infected than in controls and their peak at 16 weeks P.I. A significant difference in the IFN-gamma in the infected than in controls with peak occurred at 6 weeks P.I. and declined after that reaching a low level at 16 weeks P.I. A highly significant positive correlation was between TGF-Bland IL4 and significant negative correlation between IFN-gamma and both IL4 & TGF-B1. A highly significant and significant negative correlation between TGF-B1 and egg count at 12 & 16 weeks P.I respectively. Negative correlation was between IL-4 and egg count at 16 weeks P.I. But, significant positive correlation was between IFN-gamma with the egg count at 16 weeks P.I. A significant negative correlation was between TGF-B1 and oogram at 6 & 16 weeks P.I, but highly significant positivity was between IFN-gamma and oogram at 16 weeks P.I. A significant negative correlation was between IL-4 and oogram at 16 weeks P.I. A significant positive correlation was between levels of hydroxyproline and TGF-B1 at 12 & 16 weeks P.I. Highly significant negative correlation between hydroxyproline and IFN-gamma was at 12 weeks P.I with significant and highly significant positive correlation between hydroxyproline and IL4 at 12 & 16 weeks P.I.

Detection of altered secondary lymphoid-tissue chemkine responsiveness in Balb/c mice infected with Schistosoma mansoni.

To determine the extent to which Balb/c mice splenic T cells were affected by S. mansoni infection, this study aims to investigate the ability of the T cells to produce interferon (IFN)-&, and their chemotactic ability at 7 weeks post-infection. The splenic T cells were capable of producing levels of IFN-& comparable with splenic T cells from naive mice. However, the T cells exhibited altered chemotactic activity, as evidenced by an inability to respond to secondary lymphoid-tissue chemokine (SLC/CCL21). Although no difference in chemokine expression was found between the spleens of infected versus control mice, chemokine production was greater in the livers of infected versus control mice. Collectively, these data indicate that Balb/c mice with 7-wk S. mansoni infection possess splenic T cells with altered chemotactic activity and that the alterations may be a consequence of granulomatous response in the liver.

In vitro effect of Mirazid on Schistosoma mansoni worms.

Measuring Mirazid ability for contracting the worm muscle and its effect on the worm surface ultra-structure can be used to monitor the in vitro effect of any drug. This study aims at investigating the actual effect of Mirazid (a new schistosomicide; purified oleo-resin extract of Myrrh, derived from Commiphora molmol plant) on S. mansoni worms by detecting its in vitro effect. Three groups of white albino mice (5 mice in each group) were infected by 100 cercariae for each mouse. The 3rd group served as a control group. Seven weeks post-infection the mice were sacrificed, perfused and worms were collected. Muscle tension of the worms collected from the first group of mice, was assayed in response to Mirazid in rising concentrations of 100, 200, 300 and 400 nM. The in vitro effect of Mirazid on the muscle tension of single S. mansoni worm was determined using a special device to determine percentage of change in worm length (% shortening). The drug elicited somatic muscle contraction and reached the highest response with 400 nM Mirazid. The maximal increase in the muscle tension (48% shortening) was induced by the highest concentration (400 nM) of the drug. The worms collected from the second group of mice were scanned by electron microscopy. The worms were exposed each to 10 ul of Mirazid in concentration of 10(-6) and collected after 10, 20 and 30 minutes of exposure. Ten minutes exposure caused disruption of the tegument and collapse of tubercles. After 20 minutes, the tegument appeared edematous with more disruption and more shrinkage of tubercles. After 30 minutes, the tegument appeared markedly edematous with extensive disruption of the inter-papillary areas and sensory bulbs. The spines covering the tubercles appeared to be lost.

Assessing the morbidity of schistosomiasis by measuring eosinophil cationic protein in serum.

Eosinophil cationic protein (ECP) was recently used for assessment of Schistosoma haematobium morbidity. In this study, the level of (ECP) in sera of schistosomiasis patients was significantly higher than control group, and this significance was higher in S. haematobium than S. mansoni groups. No association between level of (ECP) in serum and egg count in S. mansoni and S. haematobium patients was found. Comparing the correlation of ECP level in serum with Schistosoma antigen in both serum and urine, in S. mansoni there was a positive association between (ECP) in serum and serum schistosomal antigen but not with schistosomal antigen level in urine among S. mansoni infected patients. On the other hand, in-patients with S. haematobium infection there is strong association between (ECP) level in serum and the level of antigen in urine, but not with schistosomal serum antigen level. These results suggest that serum (ECP) may be useful and more sensitive and accurate marker of morbidity in S. haematobium infection than indirect measures.

Parasitological and immunological changes in murine hepatic schistosomiasis before and after praziquantel treatment.

Hepatic fibrosis was assessed by estimating hydroxyproline content in liver tissues at the course of the disease and after PZQ treatment. Parasitological investigations included egg count in faeces and tissues (liver and intestine) and oogram pattern. The results showed that treatment of infected mice with PZQ, modulated the course of schistosomiasis as evaluated by highly significant decline in hepatic hydroxyproline content as well as egg count in stool and tissues. In addition, the oogram pattern showed that PZQ had a lethal effect on mature eggs in tissues. PZQ treatment of S. mansoni infected mice, is effective in reducing the severity of the disease and in attenuating hepatic fibrosis, particularly when the treatment starts early with a suitable dose.

Resistance to praziquantel, effect of drug pressure and stability test.

Various isolates of S. mansoni, originally showed marked diminished susceptibility to PZQ, were used in this work. These isolates were taken from patients not cured after two or three doses of the drug. They were passed in experimental mice and treated with sub-curative doses of PZQ to determine the effect of drug pressure on the offspring of these isolates. Upon treatment of the second generation of these isolates with curative doses of PZQ, they showed significant less response to the drug in terms of both the drug efficacy (percent of worm reduction), and the ED50 (the effective dose that kills 50% of worms). Also, stability test was performed on some S. mansoni isolates. This means repeated treatment of unsusceptible isolates that have been passed for several passages in the lab. and results compared to that of a control susceptible isolate (originally taken from a patient cured after a single dose of PZQ). The results showed that repeated passage of S. mansoni isolates in the lab. does not render them more susceptible to PZQ. Indeed, these resistant isolates showed less susceptibility to the drug than before, or at least they retain their original level of insusceptibility to PZQ.

Detection of E. histolytica, G. lamblia and Cryptosporidium copro-antigens in stool samples.

A double antibody sandwich ELISA technique, using a chromatography purified antisera against E. histolytica, G. lamblia and Cryptosporidium antigens, was applied to detect copro-antigens of the corrosponding parasites in 90 patients. All positive cases were diagnosed by parasitological examination and proved to have the infection solely. Beside the 90 positive cases, 40 age-matched controls were included in the study, of which 20 individuals were infected with other parasites but not Cryptosporidium, E. histolytica or G. lamblia (acted as an infected control group) and the other 20 individuals with no intestinal parasites (normal control group). The assay could detect 100% of those infected with both of G. lamblia and E. histolytica and 96.6% (29/30) of patients with Cryptosporidium infection. False positive reactions were detected in 3 cases using G. lamblia antisera (92.5%), 5 cases using E. histolytica antisera (87.5%) and 2 cases using Cryptosporidium antisera (95%). A direct increase in the mean antigen level was observed with the increasing intensity of infection in the 3 parasites, so higher mean O.D. readings was observed in heavily infected cases than moderately infected cases than lighter intensity of infection. Only those in elder age group (> 20 years) infected with E. histolytica were found to have statistically higher O.D. readings of the antigen than middle age group (10-20 years). On the other hand, no statistically significant difference was observed between different age groups and antigen level in cases with either G. lamblia or Cryptosporidium.