Tissue Distribution and Efficacy of Gold Nanorods Coupled with Laser Induced Photoplasmonic Therapy in Ehrlich Carcinoma Solid Tumor Model

Gold nanorods (GNR) within tumor microregions are characterized by their ability to absorb near IR light and emit heat in what is called photoplasmonic effect. Yet, the efficacy of nanoparticles is limited due to intratumoral tissue distribution reasons. In addition, distribution of GNRs to normal tissue might result in non specific toxicity. In the current study, we are assessing the intratumoral and tissue distribution of PEGylated GNRs on the top of its antitumor characteristics when given intravenously or intratumoral to solid tumor bearing mice and coupled with laser photoplasmonic sessions. PEGylated GNRs with a longitudinal size of less than 100 nm were prepared with aspect ratio of 4.6 showing strong surface plasmon absorption at wavelength 800 nm. Pharmacokinetics of GNR after single I.V. administration (0.1 mg/kg) showed very short systemic circulating time (less than 3 h). On the other hand, tissue distribution of I.V. GNR (0.1 mg/kg) to normal animals showed preferential deposition in spleen tissue. Repeated administration of I.V. GNR resulted in preferential accumulation in both liver and spleen tissues. In addition, I.V. administration of GNR to Ehrlich carcinoma tumor bearing mice resulted in similar tissue distribution; tumor accumulation and anti-tumor effect compared to intratumoral administration. In conclusion, the concentration of GNR achieved within tumors microregions after I.V. administration was comparable to I.T. administration and sufficient to elicit tumoral growth arrest when coupled with laser-aided photoplasmonic treatment.     

First record and preliminary evaluation of Mucor hiemalis as biocontrol agent on inflorescence brown rot incidence of date palm

In Egypt, inflorescence brown rot disease of date plam trees caused by Thielaviopsis paradoxa De Syenes causing high losses of pollen grains and fruits yield productivity. Infection occurs early on spathes even when it still hidden in the leaf bases. White mycelium of pathogenic fungi grows on inflorescence then turned to brown when fungus spores abundant. Isolation trails from diseased spathes showed brown rot, yielded three genus of fungal i.e. Aspergillus niger (25%), Mucor hiemalis (25%) and T. paradoxa (50%). Pathogenicity test by using fungal isolates and male inflorescence of data indicate that, all isolates of T. paradoxa were able to induce brown rot of inflorescence. Isolates of T. paradoxa were differed in pathogenic activity for producing inflorescence brown rot symptom. Also, A. niger isolate could cause slightly decay on inflorescence. Meanwhile, all isolates of M. hiemalis recorded as non pathogenic. In vitro, dual culture technique by using M. hiemalis showed antagonistic properties against T. paradoxa. Scanning electron microscopy (SEM) study revealed that, pollen grains of date palm are susceptible to infection by T. paradoxa, accompanied by complete lyses and ruptured. SEM examination of inflorescence treated by each of M. hiemalis or/and T. paradoxa showed that M. hiemalis was able to colonisation on inflorescence and reduced colonisation of T. paradoxa on inflorescence and pollen grains. Preliminary evaluation of M. hiemalis as a biocontrol agent showed that, spray of inflorescence with M. hiemalis suspension two days before or after infestation by T. paradoxa were reduced brown rot of inflorescence than the control. Spraying of spathes by M. hiemalis before infestation by pathogen was highly effective in reduction brown rot incidence compared with spraying after infestation. These results help to explain the role of M. hiemalis in the suppression and biological control of T. paradoxa.     

Aginoside saponin,a potent antifungal compound,and secondary metabolite analyses from Allium nigrum L.

The HPLC and spectral analyses of cysteine sulfoxides (CSOs), total polyphenols (TP), and total saponins revealed quantitative variations within the different organs of Allium nigrum L. A large accumulation of CSOs was detected in the bulb (0.367 mg/g fw), of TP in the leaf (116.05 mg CE/100 g fw), and of saponins in the root (19.38 mg/g dw). Phytochemical and chromatographical investigations of A. nigrum root extract led to the isolation of a spirostane-type glycoside or aginoside. The structure was elucidated by spectroscopic analysis (2D NMR, FABMS, HR-ESI-MS). The structure of the aginoside was identified as 25(R,S)-5α-spirostan-2α,3β,6β-trio1-3-O-β-d-glucopyranosyl-(1→2)-O-[β-d-xylopyranosyl-(1→3)]-O-β-d-glucopyranosyl-(1→4)-β-d-galactopyranoside. The highest content of aginoside, 2.9 mg/g dw, was detected in the root. The in vitro and in vivo antifungal activity of aginoside was evaluated for the first time against phytopathogens. This compound showed significant (P < 0.05) antifungal activity depending on the concentration.     

Unintended Harm and Benefit of the Implantable Defibrillator in an Unfortunate 19-Year-Old Male: Featuring a Sequence of Rare Life-threatening Complications of Cardiac Procedures

All procedures have inherent risk. Our patient endured a sequence of rare life-threatening complications from commonly preformed procedures. The sequence of these complications was; large pericardial effusion post implantable cardioverter-defibrillator (ICD) implantation with echocardiographic signs of tamponade, left main narrowing post radiofrequency ablation, and late stent thrombosis post coronary intervention with a bare metal stent. All these occurred to one unfortunate young man. Furthermore, our patient demonstrated an unintended benefit of ICD which saved his life.     

Synthesis and Evaluation of Antimicrobial Activity of Some Pyrimidine Glycosides

Reaction of ethyl 4-thioxo-3,4-dihydropyrimidine-5-carboxylate derivatives 1a,b and ethyl 4-oxo-3,4-dihydropyrimidine-5-carboxylate 1c with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide in KOH or TEA afforded ethyl 2-aryl-4-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosylthio or/ oxy)-6-methylpyrimidine-5-carboxylate 6a-c. The glucosides 6a and 6b were obtained by the reaction of 1a and 1b with peracetylated glucose3 under MW irradiation. Mercuration of 1a followed by reaction with acetobromoglucose gave the same product 6a. The reaction of 1a-c with peracetylated ribose 4 under MW irradiation gave ethyl 2-aryl-4-(2′,3′,5′-tri-O-acetyl-β-D-ribofuranosylthio)-6-methylpyrimidine-5-carboxylate 8a–c. The deprotection of 6a–c and 8a–c in the presence of methanol and TEA/H₂O afforded the deprotected products 7a–c and 9a–c. The structure were confirmed by using ¹H and ¹³CNMR spectra. Selected members of these compounds were screened for antimicrobial activity.     

Association between TNF promoter −308 G>A and LTA 252 A>G polymorphisms and systemic lupus erythematosus

Tumor necrosis factor (TNF) and lymphotoxin alpha (LTA) are pivotal cytokines in the pathogenesis of systemic lupus erythematosus (SLE). To investigate the possible association of the polymorphism of the TNF promoter gene ?308 and that of the LTA gene 252 with susceptibility to SLE and with phenotypic disease features in Egyptian patients. A case control study involving 100 SLE patients and 100 unrelated healthy controls. Polymerase chain reaction and restriction fragment length polymorphism methods were applied to detect genetic polymorphism. We found that TNF?308 genotype AA was significantly increase by 26 % in SLE patients compared to 10 % in the control group (p = 0.003; OR 3.16; CI 1.43–6.98) and the frequency of the A allele of the TNF promoter ?308 was significantly higher in the SLE patients (42 %) than in the control subjects (24 %) (p < 0.001; OR 2.29; 95 % CI 1.49–3.52). Genotype LTA 252 GG showed a significant increase by 22 % in SLE patients compared to 6 % in the control group (p = 0.001; OR 4.42; 95 % CI 1.71–11.44), and the frequency of the G allele of the LTA was significantly higher in the SLE patients (38 %) than in the control subjects (21 %) (p < 0.001; OR 2.31; 95 % CI 1.48–3.6). Genotype (AA+GA) of TNF was significantly associated with clinical manifestations as malar rash, arthritis, oral ulcers, serositis and systemic lupus erythematosus disease activity index. Genotype (GG+GA) of LTA was significantly associated with arthritis. These results suggest that TNF and LTA genetic polymorphisms contribute to SLE susceptibility in the Egyptian population and are associated with disease characteristics. TNF?308 and LTA+252 polymorphic markers may be used for early diagnosis of SLE and early prediction of clinical manifestations, like arthritis.     

Loss of P2Y2 Nucleotide Receptors Enhances Early Pathology in the TgCRND8 Mouse Model of Alzheimer's Disease

Neuroinflammation is a prominent feature in Alzheimer's disease (AD) and activation of the brain's innate immune system, particularly microglia, has been postulated to both retard and accelerate AD progression. Recent studies indicate that the G protein-coupled P2Y₂ nucleotide receptor (P2Y₂R) is an important regulator of innate immunity by assisting in the recruitment of monocytes to injured tissue, neutrophils to bacterial infections and eosinophils to allergen-infected lungs. In this study, we investigated the role of the P2Y₂R in progression of an AD-like phenotype in the TgCRND8 mouse model that expresses Swedish and Indiana mutations in amyloid precursor protein (APP). Our results indicate that P2Y ₂ R expression is upregulated in TgCRND8 mouse brain within 10 weeks of age and then decreases after 25 weeks of age, as compared to littermate controls expressing low levels of the P2Y ₂ R. TgCRND8 mice with homozygous P2Y ₂ R deletion survive less than 5 weeks, whereas mice with heterozygous P2Y ₂ R deletion survive for 12 weeks, a time point when TgCRND8 mice are fully viable. Heterozygous P2Y ₂ R deletion in TgCRND8 mice increased β-amyloid (Aβ) plaque load and soluble Aβ_1–42 levels in the cerebral cortex and hippocampus, decreased the expression of the microglial marker CD11b in these brain regions and caused neurological deficits within 10 weeks of age, as compared to age-matched TgCRND8 mice. These findings suggest that the P2Y₂R is important for the recruitment and activation of microglial cells in the TgCRND8 mouse brain and that the P2Y₂R may regulate neuroprotective mechanisms through microglia-mediated clearance of Aβ that when lost can accelerate the onset of an AD-like phenotype in the TgCRND8 mouse.     

Swimming exercise versus L-carnosine supplementation for Alzheimer’s dementia in rats: implication of circulating and hippocampal FNDC5/irisin

Journal of Physiology and Biochemistry - Recent studies have suggested that irisin may act as a potential neurokine. Exercise and L-carnosine supplementation showed neuroprotective effects in...