Formulation and Optimization of Orodispersible Tablets of Diazepam

Diazepam is one of the most prescribed benzodiazepines. The purpose of the present research was to optimize the formulation of orodispersible tablets of diazepam. Orodispersible tablets of diazepam were prepared using different types of superdisintegrants (Ac-Di-Sol, sodium starch glycolate, and crospovidone (CP)) and different types of subliming agents (camphor and ammonium bicarbonate (AB)) at different concentrations and two methods of tablets preparations (wet granulation and direct compression methods). The formulations were evaluated for flow properties, wetting time, hardness, friability, content uniformity, in vivo disintegration time (DT), release profiles, and buccal absorption tests. All formulations showed satisfactory mechanical strength except formula F5 which contains camphor and formula F9 which is prepared by direct compression method. The results revealed that the tablets containing CP as a superdisintegrant have good dissolution profile with shortest DT. The optimized formula F7 is prepared using 10% CP as a superdisintegrant and 20% AB as a subliming agent by wet granulation method which shows the shortest DT and good dissolution profile with acceptable stability. This study helps in revealing the effect of formulation processing variables on tablet properties. It can be concluded that the orodispersible tablets of diazepam with better biopharmaceutical properties than conventional tablets could be obtained using formula F7.     

Sodium orthovanadate induced tyrosine phosphorylation of platelet nitric oxide synthase negatively regulates enzyme activity

The post-translational regulation of platelet nitric oxide synthase (NOS) activity is poorly understood. In the present study we examined how tyrosine phosphorylation of NOS, induced by the tyrosine phosphatase inhibitor sodium orthovanadate (VO4), influenced enzyme activity. Platelet NOS was basally tyrosine phosphorylated, but incubation with VO4 (100-1000 microM) led to a concentration-dependent increase in tyrosine phosphorylation of the enzyme with maximal effects observed at 500 microM. Importantly, we observed no change in serine(1179) or threonine(497) phosphorylation. The increased tyrosine phosphorylation was associated with reduced NOS activity and NO bioavailability, as evidenced by measurement of [(3)H]-L-citrulline and cGMP respectively. The signalling events underlying the effects of VO4 were studied using specific inhibitors to kinases that are known to influence NOS activity. Preincubation of platelets with the Src kinase inhibitor PP2 (20 microM) blocked VO4-induced tyrosine phosphorylation of NOS and abolished the effects of VO4 on cGMP formation. The PKC inhibitor Ro-31-8220 (10 microM) had no effect on VO4-induced tyrosine phosphorylation, but did have a modest but significant effect on cGMP formation. In contrast, the PI-3-kinase inhibitor wortmannin (100 nM) had no effect on either tyrosine phosphorylation or cGMP formation. Our data indicate that tyrosine phosphorylation may act to repress NOS activity. Furthermore, VO4 induces a Src-dependent, and to a lesser degree PKC-dependent, inhibition of platelet NOS.     

A Mathematical Model for the Regulation of Tumor Dormancy Based on Enzyme Kinetics

In this paper we present a two-compartment model for tumor dormancy based on an idea of Zetter [1998, Ann. Rev. Med. 49, 407–422] to wit: The vascularization of a secondary (daughter) tumor can be suppressed by an inhibitor originating from a larger primary (mother) tumor. We apply this idea at the avascular level to develop a model for the remote suppression of secondary avascular tumors via the secretion of primary avascular tumor inhibitors. The model gives good agreement with the observations of [De Giorgi et al., 2003, Derm. Surgery 29, 664–667]. These authors reported on the emergence of a polypoid melanoma at a site remote from a primary polypoid melanoma after excision of the latter. The authors observed no recurrence of the melanoma at the primary site, but did observe secondary tumors at secondary sites 5–7 cm from the primary site within a period of 1 month after the excision of the primary site. We attempt to provide a reasonable biochemical/cell biological model for this phenomenon. We show that when the tumors are sufficiently remote, the primary tumor will not influence the secondary tumor while, if they are too close together, the primary tumor can effectively prevent the growth of the secondary tumor, even after it is removed. It should be possible to use the model as the basis for a testable hypothesis.     

Production Kinetics and Tensioactive Characteristics of Biosurfactant from a Pseudomonas aeruginosa Mutant Grown on Waste Frying Oils

Various waste frying oils (WFOs) were evaluated as substrates for rhamnolipid production by Pseudomonas aeruginosa mutant EBN-8 in the presence or absence of rhamnolipid precursor, under single-/batch-fed conditions. Soybean WFO was the best substrate, producing 9.3 g rhamnolipid l⁻¹ with the specific product yield of 2.7 g g⁻¹ h, under batch-fed cultivation with the addition of rhamnolipid precursor. The surface tension of the cell-free culture broth (CFCB) was 29.1 mN m⁻¹ and the interfacial tension against n-hexadecane was <1 mN m⁻¹. The hydrocarbon/ CFCB systems showed the relative emulsion stability to be in the range of 89.7–92.3.     

Spatio-Temporal Distribution of Freshwater Snail Species in Relation to Migration and Environmental Factors in an Irrigated Area from Morocco

Nine sites were sampled 19 times over 2 years in an irrigation system in Morocco in order to study species abundance in a snail community in relation to environmental parameters (including human activities) and migration (geographic distance) among sites. Each site was made of a sink and the first meters of the downstream canal. The snail community included four species (Bulinus truncatus, Lymnaea truncatula, Mercuria similis and Physa acuta). Strong spatial variation in species occurrence and abundance was detected which might be partly due to variation in water availability. However abundance in sinks and canals in which water availability differs were correlated. There was, as predicted, limited evidence in favor of isolation by distance which might be due to fast water current. Dispersal might therefore be an important factor structuring this community. On the other hand, the temporal variation was much more limited. This is consistent with the analysis of individual size distributions in B. truncatus, since no clear-cut cohorts were detected. The environmental parameters recorded (e.g. temperature, occurrence of macrophytes or cleaning of sinks) were extremely variable in time and space, except temperature. Analyzing their association with species through multidimensional methods indicated that P. acuta is ubiquitous and B. truncatus positively associated with macrophytes. These two species were associated in sinks. Less clear trends were detected for the two other species. Annual cleaning of sinks affected all species, but population recovery was fast in B. truncatus and P. acuta.     

Electrochemical DNA biosensor for the study of ciprofloxacin-DNA interaction

The interaction of ciprofloxacin with DNA was studied by using an electrochemical DNA biosensor. The binding mechanism of ciprofloxacin was elucidated by using constant current potentiometry and differential pulse voltammetry at DNA-modified glassy carbon electrode. The decrease in the guanine oxidation peak area or peak current at +0.9 V was used as an indicator for the interaction mechanism in 0.2M acetate buffer (pH 5). The binding constant (K) values obtained were 1.33+/-0.02 x 10(4) and 1.32+/-0.08 x 10(4) M(-1) with constant current potentiometry and differential pulse voltammetry, respectively. A linear dependence of the guanine peak area or peak currents was observed in the range of 40-80 microM ciprofloxacin, with a detection limit of 24 microM with r=0.995 and 9 microM with r=0.999 by using constant current potentiometry and differential pulse voltammetry, respectively. Moreover, the influence of sodium and calcium ions was also studied to elucidate the mechanism of ciprofloxacin-DNA interaction at different solution conditions, and this proved to be helpful in understanding the ciprofloxacin-DNA interaction.     

Consanguineous marriage in a newly developed country: the Qatari population

This study examines the frequency of consanguineous marriage and coefficient of inbreeding in the State of Qatar. The study was conducted in semi-urban areas of Doha between January and May 2004. A sample of 1515 married Qatari females aged 15 years and over participated. The degree of consanguinity between each female and her spouse, and degree of consanguinity between their parents were recorded. The rate of consanguinity in the present generation was high (54.0%) with a coefficient of inbreeding of 0.02706. The commonest type of consanguineous marriage was between first cousins (34.8%). Double first cousin marriages were common (3.1%) compared with other populations. The consanguinity rate in the State of Qatar has increased from 41.8% to 54.5% in one generation.     

Effects of Carbon Source and Vitreoscilla Hemoglobin (VHb) on the Production of β-Galactosidase in Enterobacter aerogenes

At fixed concentration (0.5%), lactose and galactose acted as inducers while glucose and other tested carbon sugars showed repression effects on β-galactosidase production in Enterobacter aerogenes strain. The expression of Vitreoscilla hemoglobin gene (vgb) in this bacterial strain managed to overcome the repression effects as well as improving the induction of β-galactosidase formation by carbon sources. In parallel, the bacterial O₂ consumption was increased correspondingly to the vgb induction of β-galactosidase synthesis. When Enterobacter aerogenes strains were grown at the incubation temperature 42°C, about 5-fold higher enzyme productivity was obtained than with a similar incubation at 37°C. The bacterial growth expressed as biomass yield had a different optimum temperature and was not influenced to the same extent by variations in the carbon sources. These data are discussed in terms of proposed enhancement in β-galactosidase productivity by vgb expression as well as its significance to improve the technology of whey processing.