Kalirin inhibition of inducible nitric-oxide synthase

Nitric oxide (NO) acts as a neurotransmitter. However, excess NO produced from neuronal NO synthase (nNOS) or inducible NOS (iNOS) during inflammation of the central nervous system can be neurotoxic, disrupting neurotransmitter and hormone production and killing neurons. A screen of a hippocampal cDNA library showed that a unique region of the iNOS protein interacts with Kalirin, previously identified as an interactor with a secretory granule peptide biosynthetic enzyme. Kalirin associates with iNOS in vitro and in vivo and inhibits iNOS activity by preventing the formation of iNOS homodimers. Expression of exogenous Kalirin in pituitary cells dramatically reduces iNOS inhibition of ACTH secretion. Thus Kalirin may play a neuroprotective role during inflammation of the central nervous system by inhibiting iNOS activity.     

Proinflammatory macrophage-activating properties of the novel phospholipid diacylglycerol pyrophosphate

We have found that the novel phospholipid diacylglycerol pyrophosphate (DGPP), identified in bacteria, yeast, and plants, but not in mammalian cells, is able to potently activate macrophages for enhanced secretion of arachidonate metabolites, a key event in the immunoinflammatory response of leukocytes. Macrophage responses to DGPP are specific and are not mediated by its conversion into other putative lipid mediators such as phosphatidic acid, lysophosphatidic acid, or diacylglycerol. The responses to DGPP are compatible with a receptor-recognition event because they are blocked by suramin. Intracellular signaling initiated by DGPP includes phosphorylation and activation of the Group IV cytosolic phospholipase A2 and of the extracellular-signal regulated p42 mitogen-activated protein kinase (MAPK) and p44 MAPK, and membrane translocation of the protein kinase C isoenzymes alpha, epsilon, delta. These results establish DGPP as a novel macrophage-activating factor and suggest a potential role for this compound in triggering homeostatic cellular responses.     

Compliance in pulmonary tuberculosis patients using directly observed treatment short course

Five hundred newly diagnosed cases of pulmonary tuberculosis patients were studied at Iwo Local Government tuberculosis (TB) control clinic Alaye, Iwo, Osun state of Nigeria. The study was to determine (a) the rate of compliance to antituberculous drugs in newly diagnosed pulmonary tuberculosis (PTB) patients over a 2-year period in Iwo, Nigeria treated with directly observed treatment short-course (DOTS). DOTS is a short course treatment lasting 6-8 months and (b) the effect of DOTS and the use of home visitors on compliance with a view to formulating a model that can be used all over Nigeria to stem the resurgence of PTB. All newly diagnosed cases of PTB at Iwo, Osun state of Nigeria were treated with DOTS over a two-year period. TB home visitor provided with a motorcycle was used throughout the treatment period with free drug provision by Damien Foundations of Belgium based in Ibadan, Nigeria. The rate of compliance was noted in all cases. Total (100 percent) compliance and cure rate were recorded with the use of DOTS and TB home visitor in this study. The home visitor carried out 50 visitations during the study period. The use of DOTS with free drug provision and the use of home visitor as used in this study confirmed its effectiveness in enhancing compliance and hence cure of PTB. The study is a model that can be adopted for the whole of Nigeria and other countries globally if tuberculosis must be controlled.     

Imaging of the dopaminergic neurotransmission system using single-photon emission tomography and positron emission tomography in patients with parkinsonism

Parkinsonism is a feature of a number of neurodegenerative diseases, including Parkinson's disease, multiple system atrophy and progressive supranuclear palsy. The results of post-mortem studies point to dysfunction of the dopaminergic neurotransmitter system in patients with parkinsonism. Nowadays, by using single-photon emission tomography (SPET) and positron emission tomography (PET) it is possible to visualise both the nigrostriatal dopaminergic neurons and the striatal dopamine D2 receptors in vivo. Consequently, SPET and PET imaging of elements of the dopaminergic system can play an important role in the diagnosis of several parkinsonian syndromes. This review concentrates on findings of SPET and PET studies of the dopaminergic neurotransmitter system in various parkinsonian syndromes.     

The changing presentation of pyloric stenosis

A triplet pregnancy in a 23-year-old woman was terminated at 15 weeks of gestation because of her severe hypertension, lung edema, and secondary hyperthyroidism. The pregnancy consisted of a hydatidiform mole with a 46,XY karyotype and two fetuses each with 46,XX and a 46,XY karyotype. To determine the zygosity and genetic origin of the mole and fetuses, PCR- and computer-assisted genotyping were performed at 27 CA-repeat marker loci that were distributed evenly over the genome. As a result, genotypes of the three pregnancy products were distinct from each other, indicating that the triplets were trizygotic. The mole lacked any maternal alleles but inherited both of the paternal alleles and/or one paternal allele in duplicate. This, along with the XY sex chromosome constitution, indicated that the mole resulted from dispermic androgenesis. The mother developed a persistent trophoblastic tumor thereafter.     

Segmental antigen challenge increases fibronectin in bronchoalveolar lavage fluid

Fibronectin may contribute to asthma pathogenesis by recruitment and activation of inflammatory cells, and by promotion of subepithelial fibrosis. Fibronectin is produced by several types of airway cells, including epithelial cells, fibroblasts, and alveolar macrophages. To test the hypothesis that antigen-induced airway inflammation is associated with increased local generation of fibronectin, segmental bronchoprovocation (SBP) with antigen and saline was performed in 17 atopic patients. Bronchoalveolar lavage (BAL) was performed at 5 min and 48 h after segmental challenge with saline or antigen. Fibronectin concentrations in BAL fluid, measured by enzyme-linked immunosorbent assay (ELISA), increased more than 5-fold 48 h after antigen challenge (65 [47 to 110] versus 407 [240 to 697] ng/ml, median and 25 to 75% interquartiles, p < 0.05). Fibronectin concentrations 48 h after antigen challenge correlated with histamine concentrations 5 min after antigen challenge and numbers of eosinophils, neutrophils, macrophages, and total cells in BAL fluid 48 h after antigen challenge. BAL was more enriched in fibronectin 48 h after challenge than would be predicted solely from increased permeability of plasma proteins. Western blot analysis showed that fibronectin in BAL fluid was largely intact and contained the extra domain-A (ED-A) splice variant of cellular fibronectin, indicative of local production. We conclude that antigen challenge in atopic subjects causes increased production of fibronectin by airway cells and speculate that this response may contribute to airway remodeling in allergic inflammation.     

Peripheral synapses at identified mechanosensory neurons in spiders: three-dimensional reconstruction and GABA immunocytochemistry

The mechanosensory organs of arachnids receive diverse peripheral inputs. Little is known about the origin, distribution, and function of these chemical synapses, which we examined in lyriform slit sense organ VS-3 of the spider Cupiennius salei. The cuticular slits of this organ are each associated with two large bipolar mechanosensory neurons with different adaptation rates. With intracellular recording, we have now been able to correlate directly the staining intensity of a neuron for acetylcholinesterase with its adaptation rate, thus allowing us simply to stain a neuron to identify its functional type. All rapidly adapting neurons stain more heavily than slowly adapting neurons. Immunostaining of whole-mount preparations reveals GABA-like immunoreactive fibers forming numerous varicosities at the surface of all sensory neurons in VS-3; peripheral GABA-like immunoreactive somata are lacking. Sectioning the leg nerve procures rapid degeneration of most fiber profiles, confirming that the fibers are efferent. Punctate synapsin-like immunoreactivity colocalizes to these varicosities, although some synapsin-like immunoreactive puncta are GABA-immunonegative. Fibers with similar immunoreactivities are also associated with trichobothria, tactile hairs, internal joint receptors, i.e. other types of spider mechanosensory organs. In organ VS-3, immunoreactivity is most dense across the initial axon segment. The exact distribution of peripheral synapses was reconstructed from a 10-microm-long electron micrograph series of the dendritic, somatic, and initial axon regions of acetylcholinesterase-stained VS-3 neurons. These reveal a pattern similar to that of the synapsin-like immunoreactivity. Two different types of synapse were distinguished on the basis of their presynaptic vesicle populations. Many peripheral synapses thus appear to derive from efferent GABA-like immunoreactive fibers and probably provide centrifugal inhibitory control of primary mechanosensory activities.     

Percutaneous large-core biopsy of papillary breast lesions

Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae possess the ability to cleave human IgA1 antibodies, and all successfully colonize and occasionally invade the human upper respiratory tract. N. meningitidis invades the bloodstream after a period of nasopharyngeal colonization. We directly compared levels of IgA1 protease activity in strains (n=52) derived from the cerebrospinal fluid or blood of patients with meningococcal disease with strains of N. meningitidis obtained from asymptomatic carriers (n=25). IgA1 protease activity was determined by a sensitive semiquantitative ELISA assay. Levels of IgA1 protease activity were significantly higher (P<0.0001) in strains associated with invasive meningococcal disease (98% with detectable activity, mean = 580 mU) than with those obtained from asymptomatic carriers (76% with detectable activity, mean = 280 mU). Despite marked variation in enzyme activity, almost all strains (96%) possessed the gene for IgA1 protease. Given the panmictic population structure of the bacterial isolates investigated, these data, obtained from two groups infected with N. meningitidis, but with markedly different clinical outcomes, provide the first quantitative evidence that IgA1 protease activity is a virulence determinant that contributes to the pathogenic phenotype, and suggest IgA1 protease as a potential target for prophylaxis.     

Characterization of functionalized multiwalled carbon nanotubes and application as an effective filter for heavy metal removal from aqueous solutions☆

Filtration efficiency of Ni(II) from aqueous solution using pristine and modified MWCNTs filters was investigated as a function of Ni(II) ion concentration, pH, and filter mass. MWCNTs were synthesized by CVD method and modified using two complementary treatments, purification (using a mixture of hydrochloric acid and hydrogen peroxide) and functionalization (using nitric acid). The effect and mechanism of each treatment on the structural integrity of pristine MWCNTs has been studied. Morphology of the pristine and modified filters was investigated by Raman Spectrometry (RS), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDS), Fourier Transform Infrared (FTIR) spectrometry and Thermogravimetric analysis. It was found from Raman spec-tra that the ratio of the intensity of D-band to that of G-band decreased by purification process, and increased by functionalization process. The adsorption mechanism of Ni(II) onto the surface functional groups of modified MWCNTs was confirmed by FTIR spectrum. The filtration results showed that the removal efficiency of Ni(II) is strongly dependent on pH and could reach 85%at pH=8. Also, modified MWCNT filters can be reused through many cycles of regeneration with high performance. Functionalized MWCNTs filters may be a promising adsor-bent candidate for heavy metal removal from wastewater.     

Spectrophotometric and atomic absorption spectrometric determination of ramipril and perindopril through ternary complex formation with eosin and Cu(II)

Two sensitive, spectrophotometric and atomic absorption spectrometric procedures are developed for the determination of ramipril and perindopril. Both methods are based on the formation of a ternary complex, extractable with chloroform, between copper(II), eosin and the two cited drugs. Spectrophotometrically under the optimum condition, the ternary complexes showed an absorption maximum at 535 nm, with apparent molar absorptivities of 6.55 and 4.00 x 10(3) mol(-1) x cm(-1) and Sandell's sensitivities of 5.80 x 10(-2) and 1.04 x 10(-1) microg x cm(-2) for perindopril and ramipril, respectively. The solution of ternary complex obeyed Beer's law in concentration ranges 10-60 and 20-100 microg x ml(-1) for perindopril and ramipril, respectively. The proposed method was applied to the determination of the two cited drugs in pharmaceutical tablets. The atomic absorption spectrometric method, directly through the quantitative determination of copper content of the organic extract of the complex, was also investigated for the purpose of enhancing the sensitivity of the determination. The spectrophotometric and atomic absorption spectrometric procedures hold their accuracy and precision well when applied to the determination of ramipril and perindopril dosage forms.