Role of endogenous opioids and histamine in morphine induced emesis

The role of opioid and histaminergic system in morphine induced emesis was investigated in dogs. Morphine (25 micrograms, icv) consistently evoked emesis with an average latency of 195 +/- 29 sec which was fully accounted for by an action on the chemoreceptor trigger zone (CTZ) as its ablation rendered animals refractory to vomiting. Intraventricular pretreatment with opioid antagonist naloxone, histamine H1 antagonist mepyramine and H2 antagonists metiamide and cimetidine afforded protection to icv morphine emesis. The CSF histamine concentration was significantly raised 5 min after icv morphine administration. The results suggest that both endogenous opioid and histamine are involved in morphine emesis. Naloxone in high doses (1600 micrograms, icv) elicited emesis which was not blocked by CTZ ablation confirming our earlier report.     

Plasmid-mediated drug resistance of shigellae in Kuwait

Of 153 clinical isolates of shigellae examined, 64.7% belonged toShigella flexneri, 18.9% toSh. sonnei, 11.8% toSh. boydii and 4.6% toSh. dysenteriae. Part of these isolates were resistant to sulfamethoxazole and streptomycin (88.2% each), ampicillin (66.70, tetracycline (63.40 and co-trimoxazole (43.10, with levels of resistance (MIC₅₀ and MIC₉₀) being invariably high. Resistance to three or more drugs (multidrug resistance) was seen in 77.8% of the isolates. All the 25 strains examined for transfer of resistance contained R-plasmids, both autotransferable and non-autotransferable (mobilized by transfer factor X). The frequency of transfer of different r-determinants varied from 2.7 · 10^–8 to 1.4 · 10.     

Vesicular trafficking–related proteins as the potential therapeutic target for breast cancer

Protoplasma - Vesicular trafficking between endoplasmic reticulum and Golgi plays a major role in the growth and proliferation of breast cancer cells. Various proteins regulate this ER-Golgi...     

Food Choices and Consequences for the Nutritional Status: Insights into Nutrition Transition in an Hospital Community

Introduction

Although economic development is generally accompanied by improvements in the overall nutritional status of the country’s population the ‘nutritional transition’ often involves a shift to high energy diets and less exercise with negative consequences. This pilot study was done to examine if education of parents operates at the household level to influence dietary choices and the nutritional status of children in a small community of hospital workers.

Material and Methods

3 groups of persons with varying skill and education levels participated. Weighed food logs were used in all households to calculate ‘adult equivalent’ per-capita-consumption. Nutrients were calculated using nutrients calculator software. BMI was used to classify children as underweight, normal weight and overweight.

Results

128 individuals participated from 30 families included 47 children. 10 children (21%) were underweight, 29 (62%) were normal and 8 (17%) were overweight. Energy consumption was highest in families with overweight children 2692 +/-502 compared to 2259 +/-359 in families with normal weight and 2031+/-354 in the family of underweight children. These differences were statistically significant. 42% underweight children belonged to Class 1 at the lowest skill level and there were no overweight children in this group. Most of the overweight children belonged to Class 2. In Class 3 there were no underweight children and the majority was normal weight children.

Conclusion

Underweight children came from the poorer households. Per capita intake of the family as a whole correlated well with BMI in the children. There was increased obesity in middle income families belonging to Class 2—probably in families who move up the scale from deprivation. Nutritional status in children correlated mostly with maternal education status.     

Role of traditional knowledge in marine bioprospecting

The “marine world” is endowed with diverse life forms. The life under the oceans is bestowed with a unique gene pool and characteristics owing to extreme conditions such as high salt concentration and temperature variations. The marine biodiversity is an extremely rich resource for the development of a wide array of applications in food, pharmaceuticals, cosmetics. Various forms of traditional knowledge, including traditional medicinal knowledge, have been silently developing over the centuries, with the coastal tribes in nations across the globe. Unfortunately, marine traditional knowledge has been underestimated both commercially and legally. It has still not gained its due importance at the international platform for sustainable use and development. An attempt has been made in the present study to collate information on marine traditional knowledge based medicine. Recent trends of marine bioprospecting by various nations including India have been discussed, followed by the study of legal provisions dealing with marine bioprospecting that aim at conservation and sustainable use of marine biodiversity and associated traditional knowledge. Convention of Biological Diversity, United Nations Convention on the Law of the Seas and World Intellectual Property Organization are the major international legal instruments that discuss the concepts of Prior Informed Consent, access and benefit sharing with regard to biopiracy and provide guidelines and limits for conducting marine scientific research.     

The peptaibol database: a sequence and structure resource.

The peptaibols are a large family of membrane-active peptides with considerable sequence homology, but with different biological properties and three-dimensional structures. They constitute a rich resource of naturally occurring 'mutants' which are potentially valuable for structure/function studies of ion channels. A searchable on-line database of sequences and structures of the peptaibols has been created at http://www.cryst.bbk.ac.uk/peptaibol, as a resource for the biological and structural community. In this paper, the contents and organization of the website are discussed as well as procedures for submission of new entries to the database. At present, more than 300 peptaibol sequences are stored in the database. Each sequence entry contains its full literature reference and information about its biological source. Tools are provided for searching for specific peptaibol sequences or groupings of sequences, and for locating peptaibols containing specified sequence motifs. In addition the website acts as a database for structural information. The coordinates of all currently available peptaibol x-ray and NMR structures are included and complemented, where appropriate. with molecular graphics illustrations. These include figures of model channel structures and comparisons between different peptaibol structures. The peptaibol database thus provides a tool for ready access to information and a means of investigating the sequences and structures of this class of polypeptides.     

Inhibition of neuronal apoptosis by the cyclin-dependent kinase inhibitor GW8510: identification of 3' substituted indolones as a scaffold for the development of neuroprotective drugs

Increasing evidence suggests that neuronal apoptosis is triggered by the inappropriate activation of cyclin-dependent kinases leading to an abortive re-entry of neurons into the cell cycle. Pharmacological inhibitors of cell-cycle progression may therefore have value in the treatment of neurodegenerative diseases in humans. GW8510 is a 3' substituted indolone that was developed recently as an inhibitor of cyclin-dependent kinase 2 (CDK2). We found that GW8510 inhibits the death of cerebellar granule neurons caused by switching them from high potassium (HK) medium to low potassium (LK) medium. Although GW8510 inhibits CDK2 and other CDKs when tested in in vitro biochemical assays, when used on cultured neurons it only inhibits CDK5, a cytoplasmic CDK that is not associated with cell-cycle progression. Treatment of cultured HEK293T cells with GW8510 does not inhibit cell-cycle progression, consistent with its inability to inhibit mitotic CDKs in intact cells. Neuroprotection by GW8510 is independent of Akt and MEK-ERK signaling. Furthermore, GW8510 does not block the LK-induced activation of Gsk3beta and, while inhibiting c-jun phosphorylation, does not inhibit the increase in c-jun expression observed in apoptotic neurons. We also examined the effectiveness of other 3' substituted indolone compounds to protect against neuronal apoptosis. We found that like GW8510, the VEGF Receptor 2 Kinase Inhibitors [3-(1H-pyrrol-2-ylmethylene)-1,3-dihydroindol-2-one], {(Z)-3-[2,4-Dimethyl-3-(ethoxycarbonyl)pyrrol-5-yl)methylidenyl]indol-2-one} and [(Z)-5-Bromo-3-(4,5,6,6-tetrahydro-1H-indol-2-ylmethylene)-1,3-dihydroindol-2-one], the Src family kinase inhibitor SU6656 and a commercially available inactive structural analog of an RNA-dependent protein kinase inhibitor 5-Chloro-3-(3,5-dichloro-4-hydroxybenzylidene)-1,3-dihydro-indol-2-one, are all neuroprotective when tested on LK-treated neurons. Along with our recent identification of the c-Raf inhibitor GW5074 (also a 3' substituted indolone) as a neuroprotective compound, our findings identify the 3' substituted indolone as a core structure for the designing of neuroprotective drugs that may be used to treat neurodegenerative diseases in humans.     

Reduced kidney lipoprotein lipase and renal tubule triglyceride accumulation in cisplatin-mediated acute kidney injury

Peroxisome proliferator-activated receptor-α (PPARα) activation attenuates cisplatin (CP)-mediated acute kidney injury by increasing fatty acid oxidation, but mechanisms leading to reduced renal triglyceride (TG) accumulation could also contribute. Here, we investigated the effects of PPARα and CP on expression and enzyme activity of kidney lipoprotein lipase (LPL) as well as on expression of angiopoietin protein-like 4 (Angptl4), glycosylphosphatidylinositol-anchored-HDL-binding protein (GPIHBP1), and lipase maturation factor 1 (Lmf1), which are recognized as important proteins that modulate LPL activity. CP caused a 40% reduction in epididymal white adipose tissue (WAT) mass, with a reduction of LPL expression and activity. CP also reduced kidney LPL expression and activity. Angptl4 mRNA levels were increased by ninefold in liver and kidney tissue and by twofold in adipose tissue of CP-treated mice. Western blots of two-dimensional gel electrophoresis identified increased expression of a neutral pI Angptl4 protein in kidney tissue of CP-treated mice. Immunolocalization studies showed reduced staining of LPL and increased staining of Angptl4 primarily in proximal tubules of CP-treated mice. CP also increased TG accumulation in kidney tissue, which was ameliorated by PPARα ligand. In summary, a PPARα ligand ameliorates CP-mediated nephrotoxicity by increasing LPL activity via increased expression of GPHBP1 and Lmf1 and by reducing expression of Angptl4 protein in the proximal tubule.