Metal complexation reactions of quinolone antibiotics in a quadrupole ion trap

We have undertaken a systematic study of the nature of quinolone metal complexes formed by electrospray ionization and laser desorption/ion-molecule reactions to evaluate the analytical utility of metal complexation as an alternative to conventional ionization via protonation. Metal ionization with laser-desorbed copper and nickel ions results in addition products of the form (L + Cu+) and (L + Ni+), respectively, where L is the quinolone, whereas addition-elimination products of the form (L + Co(+)-28) are observed when cobalt is used. The elimination of CO in order to form this unusual latter product seems to be favored by the formation of a cyclized structure that is stabilized by intramolecular hydrogen bonding. The CAD patterns of the Ni+ complexes prove to be the most structurally informative, more so than the fragmentation patterns of the protonated quinolones. Quinolone-metal complexes of the type [MII(L-H+)-(dipy)]+, where M is either Cu, Co, or Ni and dipy is 2,2'-dipyridine, are generated by electrospray ionization of a methanolic solution containing a quinolone antibiotic, a transition metal ion salt, and an auxiliary diimine ligand. Upon collisional activation, the ESI-generated complexes dissociate predominantly by loss of CO2, which is also the most common fragmentation pathway for the metal complexes formed through laser desorption/ion-molecule reactions. However, there are fewer structurally diagnostic fragment ions in the CAD spectra of the ESI complexes relative to those of the LD complexes.     

Inflammatory pseudotumour of the post-bulbar duodenum

This author suggests three responses to Professor Stone's call for enriching the scaffolding metaphor: (a) repositioning the metaphor in its theoretical frame; (b) considering the ways in which contexts and activities, as well as individuals, scaffold learning; and (c) examining the relationship between scaffolding and effective teaching. The author describes research that has been conducted toward these ends.     

Stress fractures of the femoral neck

Stress fractures of the femoral neck are uncommon injuries. In general these injuries are seen in two distinct populations: (1) young, healthy, active individuals such as recreational runners, endurance athletes, or military recruits; and (2) the elderly who have osteoporosis. Stress fractures can be classified as either fatigue or insufficiency fractures and result from untoward cyclic loading or impaired bone quality. The key to treatment is early diagnosis, which may require scintigraphy or magnetic resonance imaging. Nondisplaced compression type stress fractures can be treated nonoperatively with protected weight-bearing and frequent radiographic followup. Tension type stress fractures should be stabilized internally to prevent the adverse consequences of fracture displacement.     

Differential blood-brain barrier breakdown and leucocyte recruitment following excitotoxic lesions in juvenile and adult rats

Acute neuronal degeneration can be induced by intracerebral injections of the glutamate receptor agonists kainic acid (KA) and NMDA (N-methyl-D-aspartate). It is accompanied by an inflammatory response that has not yet been fully investigated. We have previously demonstrated that the juvenile rat brain is more susceptible to an inflammatory challenge when compared to adult rat brain. This study set out to investigate whether this also applied to the inflammatory response associated with acute neuronal degeneration. NMDA and kainic acid were injected into the rat striatum and lesion size, leucocyte recruitment, and blood-brain barrier (BBB) breakdown were assessed after 4, 8, 12, 24, 72, and 168 h. Both NMDA and KA induced lesions of similar volume at either age and apoptotic and necrotic nuclei could be detected. NMDA induced cellular loss by 4 h, whereas KA-injected rats did not show signs of neuronal loss until 8-12 h. The inflammatory response was characterized by an infiltration of neutrophils followed by macrophages. Juvenile rats showed a greater susceptibility to leucocyte recruitment compared to adult rats. BBB breakdown in response to NMDA injection occurred in the absence of cellular recruitment at 4 h in juveniles and was significantly greater in juvenile compared to adult rats at 8 h. BBB breakdown was minimal in KA-injected animals while at 7 days an influx of serum IgG coincided with a loss of astrocytic GFAP staining within the lesion.     

Characteristics of endogenous peptides eluted from the class I MHC molecule HLA-B7 determined by mass spectrometry and computer modeling

Microcapillary HPLC electrospray ionization tandem mass spectrometry was used to sequence 15 peptides eluted from HLA-B7. Sequence alignment implicated four peptide positions in specific interactions with the class I molecule, and their importance was confirmed using synthetic peptides. Because no crystal structure for HLA-B7 was available, computer-assisted modeling was used to understand novel aspects of peptide binding specificity and to accurately predict the effect of defined changes in peptide structure. The results demonstrate that mass-spectrometric sequencing coupled with computer-assisted modeling can be used in the absence of a crystal structure to make accurate predictions concerning requirements for peptide binding to class I molecules. These techniques may be valuable to predict or engineer T cell epitopes.     

Sternum chondroplasty in funnel-like deformity of the chest in children

A new system for manual-2 plasmocytapheresis from a medical polymer plant ready for use (Medpolymer, St. Petersburg) was evaluated in 15 donors. It makes manual-2 plasmapheresis more efficient, time-saving, and cost-effective. Its also decreases the contamination of blood components and the risk of air embolic complications. Thus, the new system may be recommended for use in transfusion medicine.     

Barriers and pathways to testing among HIV-infected women

N-acetylcysteine (NAC), the acetylated variant of the amino acid L-cysteine, is an excellent source of sulfhydryl (SH) groups, and is converted in the body into metabolites capable of stimulating glutathione (GSH) synthesis, promoting detoxification, and acting directly as free radical scavengers. Administration of NAC has historically been as a mucolytic agent in a variety of respiratory illnesses; however, it appears to also have beneficial effects in conditions characterized by decreased GSH or oxidative stress, such as HIV infection, cancer, heart disease, and cigarette smoking. An 18-dose oral course of NAC is currently the mainstay of treatment for acetaminophen-induced hepatotoxicity. N-acetylcysteine also appears to have some clinical usefulness as a chelating agent in the treatment of acute heavy metal poisoning, both as an agent capable of protecting the liver and kidney from damage and as an intervention to enhance elimination of the metals.     

Intravascular malignant lymphomatosis

Intravascular malignant lymphomatosis (IML) is a rare form of extranodal non-Hodgkin lymphoma characterized by proliferation of malignant lymphoid cells within the lumen of small blood vessels. We describe a case of IML presenting with non-specific pulmonary symptoms, weight loss, intermittent fever and a confusing collection of laboratory findings. Later on the patient developed cardiac symptoms, and finally diffuse cerebral symptoms and skin lesions. His condition deteriorated and he died within six months. The diagnosis of IML was made at autopsy. Complete remission and long-term disease-free survival may be obtained with standard chemotherapy directed at high-grade lymphomas. It is important to remember IML in the differential diagnosis of patients with confusing and changing ischaemic symptoms and signs from several organs.