Second messenger and protein phosphorylation mechanisms underlying opiate addiction: Studies in the rat locus coeruleus

We have studied the role of second messenger and protein phosphorylation pathways in mediating changes in neuronal function associated with opiate addiction in the rat locus coeruleus. We have found that chronic opiates increase levels of the G-protein subunits Gi and Go, adenylate cyclase, cyclic AMP-dependent protein kinase, and a number of phosphoproteins (including tyrosine hydroxylase) in this brain region. Electrophysiological data have provided direct support for the view that this up-regulation of the cyclic AMP system contributes to opiate tolerance, dependence, and withdrawal exhibited by these neurons. As the adaptations in G-proteins and the cyclic AMP system appear to occur at least in part at the level of gene expression, current efforts are aimed at identifying the mechanisms, at the molecular level, by which opiates regulate the expression of these intracellular messenger proteins in the locus coeruleus. These studies will lead to an improved understanding of the biochemical basis of opiate addiction.Special issue dedicated to Dr. Paul Greengard     

STADEERS: a software package for the statistical design of experiments pertaining to the estimation of parameters in rate expressions that describe enzyme-catalyzed processes

This paper describes a computational algorithm (STADEERS-STAtisticalDesign of Exeriments in Enzyme ReactorS) for the statisticaldesign of biochemical engineering experiments. The type of experimentthat qualifies for this package involves a batch reaction catalyzedby a soluble enzyme where the activity of the enzyme decayswith time. Assuming that both the catalytic action and the deactivationof the enzyme obey known rate expressions, the present codeis helpful in the process of obtaining estimates of the kineticparameters by providing as output the times at which samplesshould be withdrawn from the reacting mixture. Starting D-optimaldesign is used as a basis for the statistical approach. ThisBASIC code is a powerful tool when fitting a rate expressionto data because it increases the effectiveness of experimentationby helping the biochemical kineticist obtain data points withthe largest possible informa tional content.     

Nano-biotechnology in tumour and cancerous disease: A perspective review

In recent years, drug manufacturers and researchers have begun to consider the nanobiotechnology approach to improve the drug delivery system for tumour and cancer diseases. In this article, we review current strategies to improve tumour and cancer drug delivery, which mainly focuses on sustaining biocompatibility, biodistribution, and active targeting. The conventional therapy using cornerstone drugs such as fludarabine, cisplatin etoposide, and paclitaxel has its own challenges especially not being able to discriminate between tumour versus normal cells which eventually led to toxicity and side effects in the patients. In contrast to the conventional approach, nanoparticle-based drug delivery provides target-specific delivery and controlled release of the drug, which provides a better therapeutic window for treatment options by focusing on the eradication of diseased cells via active targeting and sparing normal cells via passive targeting. Additionally, treatment of tumours associated with the brain is hampered by the impermeability of the blood–brain barriers to the drugs, which eventually led to poor survival in the patients. Nanoparticle-based therapy offers superior delivery of drugs to the target by breaching the blood–brain barriers. Herein, we provide an overview of the properties of nanoparticles that are crucial for nanotechnology applications. We address the potential future applications of nanobiotechnology targeting specific or desired areas. In particular, the use of nanomaterials, biostructures, and drug delivery methods for the targeted treatment of tumours and cancer are explored.     

Palladium and phosphomolybdovanadate catalyzed olefin oxidation to carbonyls

A new homogeneous catalyst system has been developed for the oxidation of olefins to carbonyls — ethylene to acetaldehyde and higher olefins to ketones. The catalyst system was first developed for the oxidation of ethylene to acetaldehyde in Wacker-type acetaldehyde plants. The aqueous catalyst solution has three key components. A palladium(II) catalyst oxidizes the olefin to the carbonyl, which is analogous to the Wacker system but with only a fraction of its palladium. Keggin phosphomolybdovanadates of the general formula PMo_(12–x) V _x O ₄₀ ^(3+x)– provide a dioxygen-reversible vanadium(V)/vanadium(IV) redox agent for palladium(O) reoxidation, which is analogous to the copper(II)/copper(I) chlorides in the Wacker system. Chloride at centimolar concentrations, lacking in earlier reported palladium and polyoxometalate catalyst systems, is essential to maintain stable palladium(II) catalyst activity. Kinetic characterization and reaction engineering provided ethylene and oxygen reaction rates comparable to those obtained with the Wacker catalyst. A new, efficient method of preparing aqueous phosphomolybdovanadate solutions was developed for laboratory and large-scale production. This paper describes the catalyst system and its reactions with emphasis on the polyoxometalate chemistry.     

Antigenic variation of pilin regulates adhesion of Neisseria meningitidis to human epithelial cells

Pili have been shown to play an essential role in the adhesion of Neisseria meningitidis to epithelial cells. However, among piliated strains, both inter- and intrastrain variability exist with respect to their degree of adhesion to epithelial cells in vitro (Virji et al., 1992). This suggests that factors other than the presence of pili per se are involved in this process. The N. meningitidis pilin subunit undergoes extensive antigenic variation. Piliated low- and high-adhesive derivatives of the same N. meningitidis strain were selected and the nucleotide sequence of the pilin gene expressed in each was determined. The highly adhesive derivatives had the same pilin sequence. The alleles encoding the pilin subunit of the low-adhesive derivatives were completely different from the one found in the high-adhesive isolates. Using polyclonal antibodies raised against one hyperadhesive variant, it was confirmed that the low-adhesive piliated derivatives expressed pilin variants antigenically different from the highly adhesive strains. The role of antigenic variation in the adhesive process of N. meningitidis was confirmed by performing allelic exchanges of the pilE locus between low-and high-adhesive isolates. Antigenic variation has been considered a means by which virulent bacteria evade the host immune system. This work provides genetic proof that a bacterial pathogen, N. meningitidis, can use antigenic variation to modulate their degree of virulence.     

Piper longum Constituents Induce PANC-1 Human Pancreatic Cancer Cell Death under Nutrition Starvation

Pancreatic cancer is a highly aggressive form of cancer with a poor prognosis, partly due to ‘austerity’, a phenomenon of tolerance to nutrient deprivation and survival in its hypovascular tumor microenvironment. Anti-austerity agents which preferentially diminish the survival of cancer cells under nutrition starvation is regarded as new generation anti-cancer agents. This study investigated the potential of Piper longum constituents as anti-austerity agents. The ethanolic extract of Piper longum was found to have preferential cytotoxicity towards PANC-1 human pancreatic cancer cells in a nutrient-deprived medium (NDM). Further investigation led to the identification of pipernonaline ( 3 ) as the lead compound with the strongest anti-austerity activity, inducing cell death and inhibiting migration in a normal nutrient medium, as well as strongly inhibiting the Akt/mTOR/autophagy pathway. Therefore, pipernonaline ( 3 ) holds promise as a novel antiausterity agent for the treatment of pancreatic cancer.     

Green mass aggregations of Gyrodinium cf. aureolum Hulburt in the Ria of Pontevedra (north-west Spain)

In this paper we report a bloom of Gyrodinium cf. aureolum occurringin an estuary of the north-west coast of Spain. It was sampledin late August 1989, in shallow waters 2 m deep in the Ria ofPontevedra. Its temperature was 19.5°C and salinity 35     

Note: Influence of different heating media on thermal resistance of Neosartorya fischeri isolated from papaya fruit

E. RAJASHEKHARA, E.R. SURESH AND S. ETHIRAJ. 1996. A heat-resistant mold identified as a strain of Neosartorya fischeri was isolated from microbiologically spoiled papaya fruits. The optimum heat activation temperature and time for the ascospores of the test mold was found to be 80°C for 15–30 min. The decimal reduction times ( D -values) at 85°, 87° and 89°C in phosphate buffer (pH 7·0) as heating medium were 35·25, 11·1 and 3·90 min respectively and hence the calculated z -value was 4·0°C. In grape and mango juices as heating media, the D _80°C and the D _85°C values were increased as the °Brix level raised from 10 to 45. In commercial fruit juices of mango, orange, pineapple and mango-pineapple blend as heating media D _85°C values were greater than those observed for phosphate buffer.