Fabrication of electrospun Poly L-lactide and Curcumin loaded Poly L-lactide nanofibers for drug delivery

The present work reports the preparation of Poly L-Lactide (PLLA) and Curcumin loaded Poly L-Lactide (CPLLA) nanofibers by electrospinning. A series of PLLA solution (12 wt %) and C-PLLA (12 wt % PLLA) solution containing Curcumin (0.5 wt % and 1 wt %)) were electrospun into nanofibers. SEM images showed the average diameter of PLLA and C-PLLA in the range of 50?C200 nm. The TEM images showed the dispersion of Curcumin on C-PLLA nanofibers. The XRD pattern indicated decreases of crystallinity with the increase in the amount of Curcumin. The characteristic peak of Curcumin was confirmed by FTIR. The TGA results showed the degradation of PLLA and C-PLLA close to 300 °C. The percentage porosity and the contact angle of PLLA were found to be 90.2 % and 115±3 ° with deionised water, respectively. The water uptake percentage was found to be 17.6 %. The percentage cumulative release of Curcumin at the end of 8th day for 0.5 and 1.0 wt % formulations was 81.4±1.3 and 86.7±1.7 % respectively. The in-vitro biological cytotoxicity studies were performed using C6 glioma cells and NIH 3T3 fibroblast by MTT assay and SEM analysis.     

Preclinical evaluation of anticancer efficacy and pharmacological properties of FBA-TPQ, a novel synthetic makaluvamine analog

We have recently designed and synthesized a novel iminoquinone anticancer agent, 7-(4-fluorobenzylamino)-1,3,4,8-tetrahydropyrrolo[4,3,2-de]quinolin-8(1H)-one (FBA-TPQ) and initiated its preclinical development. Herein we investigated its efficacy, safety, and pharmacokinetics in in vitro and in vivo models of human pancreatic cancer. Our results demonstrated that FBA-TPQ inhibited pancreatic cancer cell growth, induced apoptosis, and caused cell cycle arrest in vitro. It inhibited the growth of xenograft tumors with minimal host toxicity. To facilitate future preclinical and clinical development of the agent, we also developed and validated a Rapid Resolution Liquid Chromatography (RRLC) method for quantitative analysis of FBA-TPQ in plasma and tissue samples. The method was found to be precise, accurate, and specific. Using this method, we carried out in vitro and in vivo evaluations of the pharmacological properties of FBA-TPQ, including stability in plasma, plasma protein binding, metabolism by S9 enzymes, plasma pharmacokinetics, and tissue distribution. Our results indicate that FBA-TPQ is a potential therapeutic agent for pancreatic cancer, providing a basis for future preclinical and clinical development.     

Differential Metal Binding Interactions of the Imidazolinones Revealed by NMR and UV Spectroscopy

NMR and UV spectroscopy and molecular modeling methods were applied to probe the interaction of the two imidazolinones, imazethapyr (5-ethyl-2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)nicotinic acid) and its structural isomer CL 303,135 (5-ethyl-3-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)picolinic acid), with metal ions. Both the imidazolinones inhibit the enzyme acetohydroxyacid synthase (AHAS) in vitro. However, while imazethapyr is a herbicide that is used widely in agriculture, CL303,135 does not exhibit herbicidal activity. Imazethapyr and CL303,135 exhibited considerable differences in their interactions with metals. In the metal complex of imazethapyr, the carboxyl moiety binds strongly and the pyridine nitrogen binds weakly with metals. In the case of CL303,135, both the pyridine nitrogen and the carboxyl group that are positioned ortho to each other participated strongly in the binding and were found to act together as a strong bidentate ligand to a metal ion. Both of the imidazolinones form predominantly 2:1 complexes with multivalent metal ions. However, imazethapyr binds two orders-of-magnitude more weakly (1·0×10⁹ M ^-2) with metal ions compared to CL303,135 (1·7×10¹¹ M ^-2). The interactions of the model compounds, nicotinic acid and picolinic acid, with metals were examined similarly. It was concluded that the strong affinity of CL303,135 for metals compared to imazethapyr may affect its absorption from soil into plants, or its translocation in plants, thereby explaining the differences in herbicidal activity of imazethapyr and CL303,135. © 1997 SCI.     

Anti-inflammatory activity of Syzygium cumini bark

The ethanolic extract of the bark of Syzygium cumini was investigated for its anti-inflammatory activity in animal models. The extract did not show any sign of toxicity up to a dose of 10.125 g/kg, p.o. in mice. Significant anti-inflammatory activity was observed in carrageenin (acute), kaolin-carrageenin (subacute), formaldehyde (subacute)-induced paw oedema and cotton pellet granuloma (chronic) tests in rats. The extract did not induce any gastric lesion in both acute and chronic ulcerogenic tests in rats. Thus, the present study demonstrated that S. cumini bark extract has a potent anti-inflammatory action against different phases of inflammation without any side effect on gastric mucosa.     

Clinical protection, sub-clinical infection and persistence following vaccination with extinction payloads of O1 Manisa Foot-and-Mouth Disease monovalent vaccine and challenge in goats and comparison with sheep

Small ruminants play an important role in the epidemiology of Foot-and-Mouth Disease (FMD). Small ruminants are vaccinated with one-half or one-third of cattle dose of oil-based or aqueous vaccines respectively. The extinction antigen payload in vaccine for protection in small ruminants is poorly studied. FMD seronegative Nellore sheep (n=30) and Osmanabadi goats (n=30) were vaccinated with different payloads of O(1) Manisa vaccine (0.45-5 μg). Vaccinated and sero-negative unvaccinated sheep (n=6) and goats (n=6) were challenged intradermally into the coronary band with O(1) Manisa virus. The sheep and goats were monitored for signs of FMD and samples were collected for measuring viraemia and virus associated with nasal swabs and probang samples. Clotted blood was collected for serology. Vaccines containing antigen payload up to 0.94 μg protected sheep and goats against challenge. Sheep and goats vaccinated with 0.45 μg antigen payload were poorly protected against challenge. An antigen payload of 0.94 μg was sufficient to offer complete protection and also absence of carrier status. Sheep and goats with no vaccination or with poor sero conversion to vaccination showed sub-clinical infection and became carriers. The results of the study suggest that vaccination offers protection from clinical disease even at a low payload of 0.94 μg and hence one-half of cattle dose of the oil-based vaccine formulations is sufficient to induce protective immune response in sheep and goats. Since no live virus could be isolated after 5 days post challenge from the nasal swab or probang samples even though viral RNA was detected, the risk of these animals transmitting disease was probably very low.     

Characterization of fate and transport of isoxaflutole, a soil-applied corn herbicide, in surface water using a watershed model

The objective of this study is to conduct a comprehensive assessment of the transport of isoxaflutole and RPA 202248 and their accumulation potential in semistatic water bodies, using a distributed watershed scale model and observed water quality data. A conceptual model was developed to characterize the fate and transport of isoxaflutole residues to and in surface water. The soil and water assessment tool (SWAT), a continuous daily time-step watershed model, was used to simulate the processes identified in the conceptual model. Monitoring data were available for a number of surface water bodies within the major product use area as a result of extensive and intensive residue monitoring. Detailed product use information at the zip-code level was obtained through dealer sales and a grower survey. The hydrologic and chemical transport results from the SWAT model were validated by comparison to available monitoring data from selected water bodies. Upon validation, the model was used to simulate the fate of isoxaflutole-derived residues in the water bodies using long-term historical weather data. The results from this investigation indicate no evidence of long-term accumulation of isoxaflutole and its metabolite RPA 202248 in semistatic water bodies.     

Revealing Genetic Relationship and Prospecting of Novel Donors Among Upland Rice Genotypes Using qDTY-Linked SSR Markers

A total of 17 simple sequence repeat (SSR) markers linked to QTLs (qDTYs) governing grain yield under reproductive stage (RS) drought stress were used to assess the genetic relationship and prospecting new donors for qDTYs among 32 popular upland rice genotypes. These SSR markers generated a total of 36 alleles with an average allele count of 2.1 per locus. Polymorphic information content value of the markers ranged from 0.376 to 0.662 with an average value of 0.484. The expected heterozyogosity ranged from 0.381 to 0.632. STRUCTURE analysis divided the 32 genotypes into three sub-populations. Subsequent phenotyping revealed that all the tolerant genotypes were grouped into one sub-population, whereas the moderately tolerant and susceptible genotypes were grouped into separate sub-populations. Phylogenetic tree constructed by the unweighted neighbour-joining method also divided the genotypes into three clusters. The grouping pattern of genotypes into the clusters was similar to that into the STRUCTURE analysis, on the basis of drought tolerance level. The average value of genetic dissimilarity coefficient among the genotypes was observed to be 0.486. Furthermore, by combining genotyping data with phenotyping data, 16 new donors for 6 qDTYs were identified.     

Surface drainage nitrate loading estimate from agriculture fields and its relationship with landscape metrics in Tajan watershed

Pasture, forest, and farmland are the dominant land covers in the Tajan River watershed and this landscape status has a direct connection with nitrate pollution. Understanding the correlations between landscape variables and nitrate pollutant is a priority in order to assess pollutants loading and predicting the impact on surface water quality. The soil and water assessment tool was used to simulate nitrate loads in different land cover types in different years. The landscape pattern was calculated by FRAGSTATS. The contributing share of each land use/land cover shows nitrate pollutant produced by grassland (5.7%) and forest (29%) are less than those produced by agricultural land (64.2%). Agricultural land was identified as the main source of nitrate pollution. Paddy fields and orchards had the most intensive soluble nitrate loss especially in spring and summer. Statistical analysis indicated that nitrate was positively associated with patch density, edge density, patch number, total edge, effective mesh size, largest patch index, and landscape shape index (p ≤ 0.01). We then analyzed how nitrate was related to landscape attributes in six different sites. Also the regression analysis results suggested that landscape metrics could account for more than 94% of the variance of nitrate in the whole catchment. The regression models confirmed the great importance of the agriculture metrics and forest metric in predicting nitrate in watershed. Defining the generation and extent of pollution in this particular watershed which discharges into the Caspian Sea can constitute an important step toward protecting this ecosystem.     

Validation of betapropiolactone (BPL) as an inactivant for infectious bovine rhinotracheitis (IBR) virus

Infectious bovine rhinotracheitis (IBR) virus causes vulvovaginitis, abortion and respiratory disease in cows and heifers. Betapropiolactone (BPL) is a disinfectant, effective against bacteria, fungi and viruses. It is also used to prepare inactivated vaccines because it destroys the nucleic acid core of viruses but does not damage the capsid. For the validation of BPL when used as an inactivant, it is more important to assure the quality of inactivating agent and the validity of the inactivation process. In the present study, the inactivation kinetics of IBR virus was determined with different concentration of BPL (1:250, 1:500, 1:1000, 1:1500, 1:2000 and 1:2500) at 4 and 37 °C. The result indicated that the BPL at 4 °C was able to inactivate the IBR virus within 4, 5 and 12 h with the concentration of 1:250, 1:500 and 1:1000, respectively. BPL at 37 °C was able to inactivate virus within 30 min with the concentration of 1:250. BPL with the concentration of 1:500 and 1:1000 were able to inactivate the virus within 120 min at 37 °C. Based on the kinetic study seven formulations were prepared and a sero conversion study of IBR inactivated vaccine was carried out. Serological response in animals to different formulations did not differ significantly (P > 0.05).