Role of Metal Ions and Hydrogen Bond Acceptors in the Tautomeric Equilibrium of Nitro-9[(Alkylamino)Amino]-Acridine Drugs

3-nitro-9-[2-(dialkylamino)ethyl)]aminoacridines (alkyl = methyl or ethyl) have been used as ligands towards platinum(If). The end product is a complex in which the acridine acts as a tridentate ligand contributing the two exocyclic nitrogen atoms and one of the two peri carbons. The metallation takes place predominantly at the peri position of the unsubstituted ring. The coordinated acridine is in the imino tautomeric form although, in the free state, it occurs exclusively in the amino form (both in the solid state and in solution). The imino tautomer is considered to be the biologically active form. In the platinated species the N(10)H of the acridine can be involved in strong hydrogen bonding with a chloride ion leading to formation of an association complex, the formation constant has been found to be 1.4±103 M−1. The N(10)H┄CI interaction can influence the tautomeric equilibrium of the acridine dye also in the uncoordinated species, however, the shift in favor of the imino tautomer is not complete

Role of fosfomycin tromethamine in modulating non-specific defence mechanisms in chronic uremic patients towards ESBL-producing Escherichia coli.

Antimicrobial agents and polymorphonuclear cells (PMNs) have the potential to interact in such a way that improve the therapy for infectious diseases. In immunocompromised patients highly susceptible to microbial infections with high morbidity and mortality, several metabolic and functional alterations in PMNs, mostly related to microbicidal activity, are observed. Therefore, the antibiotic of choice should have a good antimicrobial effect without impairing host defences. The aim of this study is to evaluate in vitro effects of sub-inhibiting fosfomycin tromethamine (FT) concentrations on the primary functions of PMNs from healthy subjects and immunocompromised patients (haemodialysed and renal transplant recipients), against an ESBL-producing Escherichia coli, the most common aetiological agent in urinary tract infections (UTIs). FT is considered a first line drug in the eradication of UTIs due to its appropriate antimicrobial spectrum, oral bioavailability and minimal risk of microbial resistance. Our results provide evidence that FT is able to induce enhancement of the depressed phagocytic response of PMNs from patients on chronic haemodialysis and from renal transplant recipients, restoring their primary functions in vitro against ESBL-producing E. coll All these data permit the conclusion that uremic-infected patients might additionally benefit from the immunomodulating properties of FT

Improvement of clinical response in allergic rhinitis patients treated with an oral immunostimulating bacterial lysate: in vivo immunological effects.

Allergic rhinitis is known to be one of the most common chronic diseases in the industrialized world. According to the concept that allergic rhinitis patients generally suffer from an immune deficit, in order to stimulate specifically or aspecifically their immune system, immunomodulating agents from various sources, such as synthetic compounds, tissue extracts or a mixture of bacterial extracts, have been used. The aim of the present trial is to evaluate the efficacy of the treatment with an immunostimulating vaccine consisting of a polyvalent mechanical bacterial lysate (PMBL) in the prophylaxis of allergic rhinitis and subsequently to analyze its in vivo effects on immune responses. 41 allergic rhinitis patients were enrolled: 26 patients were randomly assigned to the group for PMBL sublingual treatment and 15 others to the group for placebo treatment. For all 26 patients blood samples were drawn just before (T0) and after 3 months of PMBL treatment (T3) to evaluate plasma IgE levels (total and allergen-specific) and the cytokine production involved in the allergic response (IL-4, IFN-γ). The results of our study indicate that PMBL is effective in vivo in the reduction or in the elimination of the symptoms in rhinitis subjects during the treatment period in comparison to a non-immunostimulating treatment. A significant and clinically relevant improvement was found in 61.5%, a stationary clinical response was registered in 38.4% and no negative side effects associated with the medication or worsening were recorded. At the end of a 3-month follow up period the clinical picture remained the same as that observed at T3. PMBL treatment did not affect the serum IgE levels (either total or allergen-specific) and did not induce significant changes in IFN-γ concentration. In contrast, PMBL therapy may be accompanied, in some patients, by a potential immunomodulating activity by decreasing IL-4 cytokine expression