Complexation of norfloxacin with DNA in the presence of caffeine

1H NMR spectroscopy (500 MHz) has been used to quantify the complexation of the antibacterial antibiotic Norfloxacin (NOR) with DNA in the presence of Caffeine (CAF). Separate studies have been made for the self-association of NOR, its hetero-association with CAF and complexation with a model self-complementary DNA tetramer, 5′-d(TpGpCpA), in order to determine the equilibrium parameters (induced chemical shifts, association constants, enthalpy and entropy) of the two-component mixtures to aid the analysis of the three-component systems. Investigations of the self-association of NOR and its hetero-association with CAF show that the aggregation of NOR molecules and association with CAF in solution are driven by the stacking of aromatic chromophores. The complexation of NOR with d(TGCA) has been analysed in terms of intercalation with the double-stranded form and non-intercalative binding with the single-stranded form of DNA. Investigations of the competitive binding of NOR and CAF with DNA show that at physiological concentrations of NOR (μM) and CAF (mM) the dominant mechanism influencing the affinity of NOR with DNA is the displacement of bound NOR molecules from DNA due to CAF–DNA complexation (i.e. the protector action of Caffeine)

Catch crop strategy and nitrate leaching following grazed grass-clover

Cultivation of grassland presents a high risk of nitrate leaching. This study aimed to determine if leaching could be reduced by growing spring barley (Hordeum vulgare L.) as a green crop for silage with undersown Italian ryegrass (Lolium multiflorum Lam.) compared with barley grown to maturity with or without an undersown conventional catch crop of perennial ryegrass (Lolium perenne L.). All treatments received 0,60 or 120 kg of ammonium-N ha-1 in cattle slurry. In spring 2003, two grass-clover fields (3 and 5 years old, respectively, with different management histories) were ploughed. The effects of the treatments on yield and nitrate leaching were determined in the first year, while the residual effects of the treatments were determined in the second year in a crop of spring barley⁄perennial ryegrass. Nitrate leaching was estimated in selected treatments using soil water samples from ceramic cups. The experiment showed that compared with treatments without catch crop, green barley⁄Italian ryegrass reduced leaching by 163–320 kg Nha-1, corresponding to 95–99%, and the perennial ryegrass reduced leaching to between 34 and 86 kg Nha-1, corresponding to a reduction of 80 and 66%. Also, in the second growing season, leaching following catchcrops was reduced compared with the bare soil treatment. It was concluded that the green barley⁄Italian ryegrass offers advantages not only for the environment but also for farmers, for whom it provides a fodder high in roughage and avoids the difficulties with clover fatigue increasingly experienced by Danish farmers

De novo Cryoglobulinaemic Mononeuritis Multiplex during Treatment of Chronic Hepatitis C Infection: A Viral Effect or Induced by Pegylated Interferon Alpha?

Cryoglobulinaemic mononeuritis multiplex (MNM) is an extrahepatic manifestation of chronic hepatitis C virus (HCV) infection for which interferon-based antiviral therapy is currently the treatment of choice. Rarely MNM can be associated with HCV treatment though generally in the setting of pre-existing cryoglobulinaemia and detectable HCV viraemia. We report an unusual case of de novo MNM occurring late during the course of pegylated interferon and ribavirin therapy for chronic HCV infection, following a prolonged period of viral suppression. The patient had no evidence of cryoglobulinaemia prior to HCV treatment and undetectable HCV RNA levels at the time of presentation with MNM. The case raises the possibility that MNM could develop as an adverse immunomodulatory effect of pegylated interferon therapy

Hereditary complement factor I deficiency

Summary We describe four cases (from three families) of hereditary factor I deficiency, bringing the total number of cases now reported to 23. In one family there are two affected siblings: one has suffered recurrent pyogenic infections; the other is asymptomatic. In the second family, the patient had recurrent pyogenic infections and a self-limiting vasculitic illness; in the third family, the patient suffered recurrent pyogenic and neisserial infections. All four patients had markedly reduced concentrations of C3 in the serum (family 1 propositus: 28%; family 1 asymptomatic sibling: 15%; family 2: 31%; and family 3: 31 % normal human serum) which was in the form of C3b. Low lgG2 levels may occur in primary C3 deficiency, and reduction in lgG2 concentration to 1.14 g/l (normal: 1.30-5.90 g/l) was found in the patient from family 2. Using radioligand binding assays, we demonstrated increased binding of C3b to erythrocytes in a patient with factor I deficiency. This C3b could not be cleaved by autologous serum but could be cleaved by normal serum or purified factor I. We review and compare the published cases of C3, factor H and factor I deficienc

Calculating Casimir Energies in Renormalizable Quantum Field Theory

Quantum vacuum energy has been known to have observable consequences since 1948 when Casimir calculated the force of attraction between parallel uncharged plates, a phenomenon confirmed experimentally with ever increasing precision. Casimir himself suggested that a similar attractive self-stress existed for a conducting spherical shell, but Boyer obtained a repulsive stress. Other geometries and higher dimensions have been considered over the years. Local effects, and divergences associated with surfaces and edges have been studied by several authors. Quite recently, Graham et al. have re-examined such calculations, using conventional techniques of perturbative quantum field theory to remove divergences, and have suggested that previous self-stress results may be suspect. Here we show that the examples considered in their work are misleading; in particular, it is well-known that in two dimensions a circular boundary has a divergence in the Casimir energy for massless fields, while for general dimension $D$ not equal to an even integer the corresponding Casimir energy arising from massless fields interior and exterior to a hyperspherical shell is finite. It has also long been recognized that the Casimir energy for massive fields is divergent for $D\ne1$. These conclusions are reinforced by a calculation of the relevant leading Feynman diagram in $D$ and three dimensions. There is therefore no doubt of the validity of the conventional finite Casimir calculations.Comment: 25 pages, REVTeX4, 1 ps figure. Revision includes new subsection 4B and Appendix, and other minor correction

Local and Global Casimir Energies: Divergences, Renormalization, and the Coupling to Gravity

From the beginning of the subject, calculations of quantum vacuum energies or Casimir energies have been plagued with two types of divergences: The total energy, which may be thought of as some sort of regularization of the zero-point energy, $\sum\frac12\hbar\omega$, seems manifestly divergent. And local energy densities, obtained from the vacuum expectation value of the energy-momentum tensor, $\langle T_{00}\rangle$, typically diverge near boundaries. The energy of interaction between distinct rigid bodies of whatever type is finite, corresponding to observable forces and torques between the bodies, which can be unambiguously calculated. The self-energy of a body is less well-defined, and suffers divergences which may or may not be removable. Some examples where a unique total self-stress may be evaluated include the perfectly conducting spherical shell first considered by Boyer, a perfectly conducting cylindrical shell, and dilute dielectric balls and cylinders. In these cases the finite part is unique, yet there are divergent contributions which may be subsumed in some sort of renormalization of physical parameters. The divergences that occur in the local energy-momentum tensor near surfaces are distinct from the divergences in the total energy, which are often associated with energy located exactly on the surfaces. However, the local energy-momentum tensor couples to gravity, so what is the significance of infinite quantities here? For the classic situation of parallel plates there are indications that the divergences in the local energy density are consistent with divergences in Einstein's equations; correspondingly, it has been shown that divergences in the total Casimir energy serve to precisely renormalize the masses of the plates, in accordance with the equivalence principle.Comment: 53 pages, 1 figure, invited review paper to Lecture Notes in Physics volume in Casimir physics edited by Diego Dalvit, Peter Milonni, David Roberts, and Felipe da Ros

Solving the Graceful Exit Problem in Superstring Cosmology

We briefly review the status of the ``graceful exit'' problem in superstring cosmology and present a possible resolution. It is shown that there exists a solution to this problem in two-dimensional dilaton gravity provided quantum corrections are incorporated. This is similar to the recently proposed solution of Rey. However, unlike in his case, in our one-loop corrected model the graceful exit problem is solved for any finite number of massless scalar matter fields present in the theory.Comment: 8 pages, RevTex. Based on talk given at Conference on Big Bang and Alternative Cosmologies: A Critical Appraisal, Bangalore, India, January, 199

Characterization of staphylococcal cassette chromosome mec elements from methicillin-resistant Staphylococcus pseudintermedius infections in Australian animals

We examined the oxacillin resistance phenotype and genomic structure of staphylococcal cassette chromosome mec (SCCmec) elements from 77 veterinary methicillin-resistant Staphylococcus pseudintermedius (MRSP) isolates. Isolates were characterized by oxacillin broth microdilution, whole-genome sequencing, and bioformatics analysis. Five previously described SCCmec elements, and a sixth novel element, were identified: SCCmec III (also known as II-III), ΨSCCmec57395, and SCCmecNA45 (a SCCmec VII variant), all previously described in MRSP, and SCCmec IVg and SCCmec VT, previously described in both methicillin-resistant Staphylococcus aureus (MRSA) and MRSP. The sixth element was novel and found among nine geographically clustered isolates. This novel pseudostaphylococcal cassette chromosome (ΨSCCmecKW21) contained a class A mec gene complex but lacked ccr genes. It also harbored heavy metal (cadmium) resistance determinants. The median oxacillin MIC values among ΨSCCmecKW21, SCCmec III, and SCCmec VT isolates were significantly higher than those determined for the SCCmecNA45 VII variant isolates and ΨSCCmec57395 and SCCmec IVg isolates. ΨSCCmecKW21 was found exclusively in sequence type 497 (ST497), an MRSP clone that is locally successful in Victoria, Australia. Future studies are necessary to determine if this clone has disseminated further afield and if ΨSCCmecKW21 has moved into other MRSP lineages or staphylococcal species. IMPORTANCE Staphylococcus pseudintermedius is a significant veterinary pathogen and occasional cause of infections in humans. β-Lactams are an important group of antimicrobials used to treat staphylococcal infections in humans and animals. However, when staphylococci become methicillin resistant via the acquisition of a mobile genetic element called staphylococcal cassette chromosome mec (SCCmec), they become resistant to all β-lactams. This study detected a novel SCCmec element among a cluster of methicillin-resistant S. pseudintermedius isolates from animals in Australia. It also detected SCCmec elements in S. pseudintermedius that had high similarity to those identified in methicillin-resistant Staphylococcus aureus, demonstrating how human and animal pathogens can share the same resistance determinants