Past and present scenario of imaging infection and inflammation: a nuclear medicine perspective

AbstractNuclear medicine techniques provide potential non-invasive tools for imaging infections and inflammations in the body in a precise way. These techniques are further exploited by the use of radiopharmaceuticals in conjunction with imaging tests such as scintigraphy and positron emission tomography. Improved agents for targeting infection exploit the specific accumulation of radiolabeled compounds to understand the pathophysiologic changes involved in the inflammatory process and correlate them with other chronic illnesses. In the recent past, a wide variety of radiopharmaceuticals have been developed, broadly classified as specific radiopharmaceuticals and nonspecific radiopharmaceuticals. New developments in positron emission (leveraging 18F and 18fluorodeoxyglucose) and heterocyclic/peptide chemistry and radiochemistry are resulting in unique agents with high specific activity. Various approaches to visualizing infection and inflammation are presented in this review, in an integral manner, that give a clear view of the existing radiopharmaceuticals in clinical practice and those under development.     

Assessment of Polycyclic Aromatic Hydrocarbons (PAH) and Heavy Metals in the Vicinity of an Oil Refinery in India

Petroleum products are one of the major sources of energy for industry and daily life. Growth of the petroleum industry and shipping of petroleum products has resulted in the pollution. Populations living in the vicinity of oil refinery waste sites may be at greater risk of potential exposure to polycyclic aromatic hydrocarbons (PAH) through inhalation, ingestion, and direct contact with contaminated media. PAH have often been found to coexist with environmental pollutants including heavy metals due to similar pollution sources. The levels and distribution patterns of Σ16 PAH (sum of the 16 PAH) and heavy metals (lead, copper, nickel, cobalt, and chromium) were determined in soil and sediment in the vicinity (5 km radius) of an oil refinery in India. Concentrations of Σ16 PAH in the soils and sediments were found to be 60.36 and 241.23 ppm, respectively. Higher amount of PAH in sediments as compared to soil is due to low water solubility of PAH, settled in the bottom of aquatic bodies. The levels of lead, copper, nickel, cobalt, and chromium (total) in soil were 12.52, 13.52, 18.78, 4.84, and 8.29 ppm, while the concentrations of these metals in sediments were 16.38, 47.88, 50.15, 7.07, and 13.25 ppm, respectively. Molecular diagnostics indices of PAH (Ratio of Phenanthrene/Anthracene, Fluranthene/Pyrene) calculated for soil and sediment samples indicate that the oil refinery environment is contaminated with PAH from petrogenic as well as pyrolytic origin and heavy vehicular traffic on the Agra- Delhi National highway. Sixteen PAH priority pollutants were detected in the United States in entire samples collected near oil refinery areas and concentrations of Σ16 PAH in soil was found to be 1.20 times higher than the threshold value for PAH in soil by ICRCL (Inter-Departmental Committee on the Redevelopment of Contaminated Land). This concentration could lead to disastrous consequences for the biotic and abiotic components of the ecosystem and may affect the soil quality, thus impairing plant growth and its bioaccumulation in food chain.     

The Saccharomyces cerevisiae YLL012/YEH1, YLR020/YEH2, and TGL1 genes encode a novel family of membrane-anchored lipases that are required for steryl ester hydrolysis

Sterol homeostasis in eukaryotic cells relies on the reciprocal interconversion of free sterols and steryl esters. The formation of steryl esters is well characterized, but the mechanisms that control steryl ester mobilization upon cellular demand are less well understood. We have identified a family of three lipases of Saccharomyces cerevisiae that are required for efficient steryl ester mobilization. These lipases, encoded by YLL012/YEH1, YLR020/YEH2, and TGL1, are paralogues of the mammalian acid lipase family, which is composed of the lysosomal acid lipase, the gastric lipase, and four novel as yet uncharacterized human open reading frames. Lipase triple-mutant yeast cells are completely blocked in steryl ester hydrolysis but do not affect the mobilization of triacylglycerols, indicating that the three lipases are required for steryl ester mobilization in vivo. Lipase single mutants mobilize steryl esters to various degrees, indicating partial functional redundancy of the three gene products. Lipase double-mutant cells in which the third lipase is expressed from the inducible GAL1 promoter have greatly reduced steady-state levels of steryl esters, indicating that overexpression of any of the three lipases is sufficient for steryl ester mobilization in vivo. The three yeast enzymes constitute a novel class of membrane-anchored lipases that differ in topology and subcellular localization.     

Role of Salmonella surface components in immunomodulation of inflammatory mediators

Salmonella enterica serovar Typhimurium and its surface components were assessed for their inflammatory potential by footpad oedema test using plethysmometer. Inflammation was found to be the highest when outer membrane proteins (OMPs) were used as inflammagen followed by lipid associated protein-lipopolysaccharide complex (LAP-LPS) and lipopolysaccharides (LPS). Inflammation produced by OMPs was found to be comparable to that by carrageenan (a known positive inflammagen). However, injection of L-histidine (an antioxidant) prior to administration of carrageenan or Salmonella enterica serovar Typhimurium inhibited the inflammation, which indicated the involvement of oxidants during inflammatory response. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and nitric oxide (NO) production by peritoneal macrophages from infected mice exhibited a significant increase as compared to those of the immunized mice. In contrast, glutathione production was found to be the maximum in the macrophages taken from OMPs-immunized mice followed by LAP-LPS and LPS alone. The biochemical studies correlated well with histopathological studies of intestinal tissue of animals from various groups. Based upon these parameters, inflammation seems to be modulated by OMPs and LAP-LPS, which may be because of the protein moieties present in the components. Hence, immunization with protein moieties having L-histidine or L-histidine-like structures may suggest an alternative to the potential therapeutic values of anti-inflammatory drugs. Thus the results of this study form the basis for evaluating these antigens (either alone or in combination with polysaccharides) for preventive intervention rather than therapeutic. (Mol Cell Biochem 270: 167–175, 2005)     

Carbonic anhydrase in relation to higher plants

The review incorporates recent information on carbonic anhydrase (CA, EC: 4.2.1.1) pertaining to types, homology, regulation, purification, in vitro stability, and biological functions with special reference to higher plants. CA, a ubiquitous enzyme in prokaryotes and higher organisms represented by four distinct families, is involved in diverse biological processes, including pH regulation, CO₂ transfer, ion exchange, respiration, and photosynthetic CO₂ fixation. CA from higher plants traces its origin with prokaryotes and exhibits compartmentalization among their organs, tissues, and cellular organelles commensurate with specific functions. In leaves, CA represents 1–20 % of total soluble protein and abundance next only to ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBPCO) in chloroplast, facilitating CO₂ supply to phosphoenol pyruvate carboxylase in C₄ and CAM plants and RuBPCO in C₃ plants. It confers special significance to CA as an efficient biochemical marker for carbon sequestration and environmental amelioration in the current global warming scenario linked with elevated CO₂ concentrations.     

Rab11 is required during Drosophila eye development

In an effort to identify the role of Rab11, a small GTP binding protein, during Drosophila differentiation, phenotypic manifestations associated with different alleles of Rab11 were studied. The phenotypes ranged from eye-defects, bristle abnormalities and sterility to lethality during various developmental stages. In this paper, our focus is targeted on eye defects caused by Rab11 mutations. A novel P-element insertion in the Rab11 locus, Rab11mo, displayed characteristic retinal anomalies, which could be reverted by P-element excision and expression of Rab11+ transgenes. During larval development, Rab11 is widely synthesized in photoreceptor cells and localizes to the rhabdomeres and lamina neuropil in adult eyes. Photoreceptors and associated bristles failed to be formed in homozygous clones generated in Rab11EP(3)3017 eyes. Decreased levels of Rab11 protein and increased cell death in Rab11mo third-instar larval eye-antennal discs suggest that the retinal defects originate during larval development. Our data indicate a requirement for Rab11 in ommatidial differentiation during Drosophila eye development.