Nanoparticles as a Novel Tool to Inhibit Inflammatory Cytokines in Human Lymphocytes and Macrophages of Coronary Artery Disease.

TNFα and NF-kB contribute in activation of pro-inflammatory signaling pathways and complications of coronary artery diseases (CAD). Current study highlights novel properties of Au (15 ± 2 nm), ZnO (77 ± 45 nm) and MgO (11 ± 4 nm) nanoparticles (NPs) as possible anti-inflammatory agents with greater efficacy and lower toxicity. Decrease in TNFα and NF-kB levels in Single Vessel Disease (SVD), Double Vessel Disease (DVD) and Triple-Vessel coronary artery disease (TVD) macrophage and lymphocyte cultures at varying concentrations of NPs has been studied to find an effective therapeutic concentration (ETC). Au and MgO NPs exhibits 5 µg/ml ETC compared to 1 µg/ml ZnO in all three CAD categories with negligible toxicity. ZnO remains most statistically significant (p < 0.001) in SVD and TVD cultures whereas MgO shows efficacy in DVD and TVD cultures with more than 50% reduction in TNFα and NF-kB levels at their respective ETCs. Au NPs exhibit prominent effect in DVD cultures. The mRNA expression results support the down-regulation of TNFα and NF-kB after NPs exposure in respective cultures. Findings of this prospective observational cohort study suggest use of NPs as an alternate anti-inflammatory agent in coronary artery and other diseases.

Superparamagnetic bimetallic iron-palladium nanoalloy: synthesis and characterization.

Iron-palladium nanoalloy in the particle size range of 15-30 nm is synthesized by the relatively low temperature thermal decomposition of coprecipitated [Fe(Bipy)(3)]Cl(2) and [Pd(Bipy)(3)]Cl(2) in an inert ambient of dry argon gas. The silvery black Fe-Pd alloy nanoparticles are air-stable and have been characterized by EDX-RF, XRD, AFM, TEM, magnetometry, (57)Fe Mössbauer and impedance spectroscopy. This Fe-Pd nanoalloy is in single phase and contains iron sites having up to 11 nearest-neighboring atoms. It is superparamagnetic in nature with high magnetic susceptibility, low coercivity and hyperfine field.

Autografting as a risk factor for persisting iron overload in long-term survivors of acute myeloid leukaemia.

We studied the iron status of 32 evaluable adult acute myeloid leukaemia (AML) survivors who were entered into the UK Medical Research Council acute myeloid leukaemia (AML) 10 and 12 trials at our institution between 1988 and 1998. Patients were required to have been independent of all blood products for at least 3 years. As a group, the median first serum ferritin level was 1323 mug/l (NR 19-300 mug/l) at a median of 1321 days from the last transfusion confirming the presence of significant iron overload persisting for some years after completion of all therapy and blood products. There was a general trend for the serum ferritin level to fall with time, but the fall was less pronounced in men and carriers of the C282Y mutation. Recipients of autologous stem cell transplantation (SCT) had a higher median first serum ferritin level (3245 mug/l) than patients who received chemotherapy alone (1148 mug/l) or allogeneic SCT (1334 mug/l) because of increased use of transfused blood. Nine of the 10 recipients of autologous SCT underwent venesection. No evidence of end organ damage was seen in any patient. Serial monitoring of serum ferritin and assessment of the C282Y status may be useful in all long-term AML survivors, especially autograft recipients.

High frequency of positive surveillance for cytomegalovirus (CMV) by PCR in allograft recipients at low risk of CMV.

Cytomegalovirus (CMV) causes significant morbidity and mortality following allogeneic haemopoietic stem cell transplantation. A pre-emptive strategy for ganciclovir therapy is widely used, where treatment is commenced on finding positive evidence of CMV replication. Surveillance by PCR has increased the sensitivity for CMV detection, but it is not known whether this may detect cases with evidence of CMV DNAemia who have a low probability of CMV disease. We reviewed our experience of CMV infection and disease since introducing CMV surveillance by PCR. All 30 allografts received bedside leucodepleted CMV-negative blood products. Seven of 10 CMV-positive recipients of a CMV-positive graft developed CMV DNAemia, with three developing clinical disease requiring ganciclovir treatment. In contrast, of 11 low risk patients (CMV-negative recipients of CMV-negative grafts), six developed evidence of CMV DNAemia although only one had clinical evidence of CMV disease requiring ganciclovir. Transfusion records confirmed that four of these had received exclusively CMV-negative blood products. The aetiology of the CMV DNAemia in these cases is unclear. It is suggested that before commencing ganciclovir therapy, confirmatory CMV antigenaemia testing is carried out on samples which test positive for CMV DNA, unless there is high clinical suspicion of CMV disease.

Endogenous peptides that inhibit brain cyclic AMP phosphodiesterase.

Peptide extracts of rat brain powerfully inhibited the cyclic AMP phosphodiesterase activity of rat brain homogenate. Similar extracts of ox brain showed comparable although less potent activity. Preliminary investigation of the physicochemical properties of brain extracts indicated that the rat brain extract contained an active peptide of low molecular weight (about 1400), whereas ox brain contained two such peptides (about 1400 and 900). These studies indicate that endogenous oligopeptides that inhibit cyclic AMP phosphodiesterase are present in brain. Experiments on several pure peptides known to be present in brain. Experiments on several pure peptides known to be present in the CNS showed that the majority were inactive against brain phosphodiesterase, but ACTH(1-24), somatostatin, substance P and Lys8-vasopressin, in descending order of potency, were active. To help distinguish the peptides found in rat and ox brain extracts from known peptides, preliminary analyses of amino acid composition were performed. These suggested that the peptides found in brain extracts were distinct from known peptides having the ability to inhibit cyclic AMP phosphodiesterase.

Mechanism of quasi-morphine withdrawal behaviour induced by methylxanthines.

Of 7 phosphodiesterase inhibitors tested for ability to induce a quasi-morphine withdrawal syndrome (QMWS) in opiate-naive rats, five were effective in a dose-related way. These, in descending order of potency, were IBMX, ICI-63197, RO-201724, theophylline and caffeine. Their potencies in inducing a QMWS correlated significantly (P less than 0.05) with those in inhibiting low Km cyclic AMP phosphodiesterase of rat brain homogenate. There was no correlation with potencies in inhibiting cyclic GMP phosphodiesterase.

Endogenous inhibitor of prostaglandin synthetase.

Mammalian serum and plasma contain an endogenous inhibitor of prostaglandin synthetase (EIPS). Human plasma fractions rich in EIPS show anti-inflammatory activity in vivo. In rats, glucocorticoids raise EIPS activity of plasma and serum. These findings suggest the existence of a natural mechanism of controlling prostaglandin synthesis, possibly related to corticosteroid action.