Differential growth of the freshwater mussel, Lamellidens marginalis in relation to certain drugs

The survival and growth rate of the Indian freshwater mussel, Lamellidens marginalis, (Lamarck) was ascertained in cultivation by using certain drugs in CIFA, fish farm, BBSR (India) during June 1998 to February 1999.Two sets of experiments were carried out to evaluate the effects of drugs like Betamethasone, Calcium, Azathioprine, Stanazolol, and Folic acid. Chloramphenicol was added with each treatment as prophylaxis to prevent the bacterial growth. In the first set, the inactiveness and mortality of the mussels in different drugs were studied through two different dosages and in subsequent tests the fixation of dosage was employed. The study in the second set was regarding the survival, increment of shell length, its thickness, and wet weight in response to different drugs therapy. The drugs were administered parenterally in "fixed dosage" at a regular interval of 21-23 days. The survival rate was good with Betamethasone and Azathioprine that is 75%, whereas it was 16.66% in Folic acid treatment. But the mussels originating from the control site had the significant survival rate though the growth rate was average. Calcium treatment had shown a marked increment of shell thickness and luster. The culture was lasted for 160 days. The wet weight gain of mussels in all the treatments were significant, p<0.0001 whereas increment of shell thickness was significant only in treatment B (Calcium) and treatment D (Azathioprine), p<0.0001 but with regard to the increment of length of mussel, treatment E (Stanazolol) was not significant, p>0.05. The regression analysis was adopted to find out the coefficient of determination (R(2)=0.90, being the best) from the relationship between length and weight of mussels and to establish the LWR equation with condition factor k=W/L(b).     

Response of antioxidant enzymes in coontail (Ceratophyllum demersum L.) plants under cadmium stress

Cadmium (Cd) contamination of aquatic systems is of major concern since it is a nonessential element and hampers plant growth upon accumulation. The aim of this study was to investigate the Cd accumulation behavior of coontail plant, Ceratophyllum demersum L., toxicity induced and response of the antioxidant system. Plants were exposed to various concentrations of Cd (0-10 microM) for a period of 1-7 days. Accumulation of Cd was found to be a concentration duration dependent phenomenon. The maximum accumulation of Cd, 1293 microg g(-1) dw, was observed after 7 days at 10 microM. Plants showed significant stimulation of the activities of various antioxidant enzymes viz., superoxide dismutase (EC 1.15.1.1), ascorbate peroxidase (EC 1.11.1.11), guaiacol peroxidase (EC 1.11.1.7), catalase (EC 1.11.1.6), and glutathione reductase (EC 1.6.4.2) and tolerated toxicity of Cd up to moderate concentration of 5 microM. At 10 microM exposure, enzyme activities declined and plants experienced toxicity, which was evident by the significant decrease in the photosynthetic pigments and by increase in the levels of H(2)O(2), lipid peroxidation and ion leakage. In conclusion, modulation of antioxidant system in a coordinated manner in response to Cd accumulation appears to help plants tolerate toxicity of Cd up to 5 microM.     

Alginate-chitosan film for ocular drug delivery: effect of surface cross-linking on film properties and characterization

The characteristics of alginate-chitosan films intended for ocular drug delivery of gatifloxacin sesquihydrate were compared with the ionically surface cross-linked films of similar compositions. The effect of polymer ratios and cross-linking was studied relatively to various parameters of formulations including physicochemical, mechanical strength, swelling and bioadhesion. The drug release profiles and drug release mechanisms were compared. The folding endurance, tensile strength, bioadhesive strength considerably increased whereas swelling index, elongation at break decreased with surface cross-linking of the films. Surface cross-linked formulation F3 (2% w/v sodium alginate and 1% w/v chitosan) showed most prolonged drug release of 24 h indicating the potential of surface cross linking of the film to sustain drug release. As per the kinetic models both type of films showed a constant drug release, however the drug release mechanism transformed from erosion to diffusion after cross linking. These results demonstrate that the surface treated alginate-chitosan film could be a potential vehicle to enhance ocular GS bioavailability and patient compliance.     

Discovery of orally bioavailable 1,3,4-trisubstituted 2-oxopiperazine-based melanocortin-4 receptor agonists as potential antiobesity agents

A study that was designed to identify plausible replacements for highly basic guanidine moiety contained in potent MC4R agonists, as exemplified by 1, led to the discovery of initial nonguanidine lead 5. Propyl analog 23 was subsequently found to be equipotent to 5, whereas analogs bearing smaller and branched alkyl groups at the 3 position of the oxopiperazine template demonstrated reduced binding affinity and agonist potency for MC4R. Acylation of the NH2 group of the 4F-D-Phe residue of 3-propyl analog 23 significantly increased the binding affinity and the functional activity for MC4R. Analogs with neutral and weakly basic capping groups of the D-Phe residue exhibited excellent MC4R selectivity against MC1R whereas those with an amino acid had moderate MC4R/MC1R selectivity. We have also demonstrated that compound 35 showed promising oral bioavailability and a moderate oral half life and induced significant weight loss in a 28-day rat obesity model.     

Role of voltage-dependent potassium channels and myo-endothelial gap junctions in 4-aminopyridine-induced inhibition of acetylcholine relaxation in rat carotid artery

The present study examined the role of voltage-gated potassium (K(v)) channels and myo-endothelial gap junctions in 4-aminopyridine-induced inhibition of acetylcholine-evoked endothelium-dependent relaxation and NO release in the rat carotid artery. The acetylcholine-induced relaxation was drastically inhibited by 94% and 82%, respectively in the presence of either 100 microM N(G)-nitro-l-arginine methyl ester (L-NAME) or 10 microM 1H-[1,2,4]oxadiazolo[4,3,a]quinoxalin-1-one (ODQ), while it was abolished following endothelium removal. 4-aminopyridine (1 mM), a preferential blocker of the K(v) channels significantly decreased the vasodilator potency, as well as efficacy of acetylcholine (pD(2) 5.7+/-0.09, R(max) 86.1+/-3.5% versus control 6.7+/-0.10 R(max) 106+/-3.5%, n=6), but had no effect on the relaxations elicited by either sodium nitroprusside (SNP) or 8-bromo-cyclic guanosine monophosphate (8-Br-cGMP). 4-AP (1 mM) also inhibited acetylcholine (3 microM)-stimulated nitrite release in the carotid artery segments (99.4+/-4.93 pmol/mg tissue weight wt; n=6 versus control 123.8+/-7.43 pmol/mg tissue weight wt, n=6). 18alpha-glycyrrhetinic acid (18alpha-GA, 5 microM), a gap junction blocker, completely prevented the inhibition of acetylcholine-induced relaxation, as well as nitrite release by 4-AP. In the pulmonary artery, however antagonism of acetylcholine-evoked relaxation by 4-AP was not reversed by 18alpha-GA. These results suggest that 4-AP-induced inhibition of endothelium-dependent relaxation and NO release involves electrical coupling between vascular smooth muscle and endothelial cells via myo-endothelial gap junctions in the rat carotid artery, but not in the pulmonary artery. Further, direct activation of 4-AP-sensitive vascular K(v) channels by endothelium-derived NO is not evident in the carotid blood vessel, while this appears to be an important mechanism of acetylcholine-induced relaxation in the pulmonary artery.     

Characterization and optimization of a rhamnolipid from Pseudomonas aeruginosa C1501 with novel biosurfactant activities

An active biosurfactant-producer from an agronomic environment majorly from the rhizosphere of a wheat plant in western Nigeria was utilized for the production of rhamnolipid. The isolated bacteria were selected using different methods such as oil displacement test, emulsification activity, and surface tension respectively. Based on partial sequenced 16S rDNA analysis of isolate, C1501 was identified as Pseudomonas aeruginosa with an accession number KF976394 having 100% similarity to P. aeruginosa LMG 1242T. The results showed that Pseudomonas aeruginosa has the ability to grow and reduce surface tension under a wide range of pH and carbon source. It was observed that strain C1501 reduced the surface tension of glycerol than glucose at the various concentration tested. The surface tension of 61.2 dynes/cm was also reduced to 30 dynes/cm at 12 h after the inoculation. The biosurfactant obtained from strain C1501 was purified and characterized using TLC, Liquid Chromatography/Mass Spectrometry (LC–MS) and nuclear magnetic resonance spectroscopy (NMR). The gravimetric analysis showed that strain C1501 efficiently biodegrade the tested crude oil with the following degradation percentage of 33%, 71.3% and 96% on 5th, 10th and 20th day respectively. The biosurfactant did not exhibit an inhibitory effect on the seed of economic crops tested, but demonstrated some broad antimicrobial activities against gram positive, gram negative and rot-inducing fungus when compared to the synthetic surfactant from Tween 20. New isomers and congeners rhamnolipids were detected from the Liquid Chromatography/Mass Spectrometry (LCMS). The predicted structure of the rhamnolipid was found to be L-rhamnosyl-L-rhamnosyl-3-b-hydroxydodecenoate. The study suggests application of the strain C1501 biosurfactant as an appropriate candidate for many applications such as biomedical, food industries, agriculture, and bioremediation     

Dendrimer-mediated approaches for the treatment of brain tumor

Worldwide, the cancer appeared as one of the most leading cause of morbidity and mortality. Among the various cancer types, brain tumors are most life threatening with low survival rate. Every year approximately 238,000 new cases of brain and other central nervous system tumors are diagnosed. The dendrimeric approaches have a huge potential for diagnosis and treatment of brain tumor with targeting abilities of molecular cargoes to the tumor sites and the efficiency of crossing the blood brain barrier and penetration to brain after systemic administration. The various generations of dendrimers have been designed as novel targeted drug delivery tools for new therapies including sustained drug release, gene therapy, and antiangiogenic activities. At present era, various types of dendrimers like PAMAM, PPI, and PLL dendrimers validated them as milestones for the treatment and diagnosis of brain tumor as well as other cancers. This review highlights the recent research, opportunities, advantages, and challenges involved in development of novel dendrimeric complex for the therapy of brain tumor.     

QSAR model development for studying carbonic anhydrase inhibitors as anticonvulsant agents

The objective of this work was to develop quantitative structure activity relationship (QSAR) models from sulfonamide derivatives against anticonvulsant activity. For developing the model, multiple linear regression and artificial neural network (ANN) have been employed as effective and efficient methods and these models have been validated with statistical analysis such as fraction of variance, cross-validation test, quality factor, Fischer’s test, and internal validation test (Y-randomization test), where applicable. A regression-based QSAR model (linear model) has been developed with cross-validation test q ²?=?0.8324 and fraction of variance r ²?=?0.8327, all the statistical tests have validated this model. An ANN (nonlinear model)-based model has also been developed with fraction of variance r ²?=?0.8710 and cross validation test q ²?=?0.7032. So, with the help of the developed models we can predict the logKi values of novel designed molecules and alter their structural properties accordingly before synthesizing them.     

Design and synthesis of some new 1-phenyl-3/4-[4-(aryl/heteroaryl/alkyl-piperazine1-yl)-phenyl-ureas as potent anticonvulsant and antidepressant agents

A series of 1-phenyl-3/4-[4-(aryl/heteroaryl/alkyl-piperazine1-yl)-phenyl-urea derivatives (29–42) were designed, synthesized and evaluated for their anticonvulsant activity by using maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) seizure tests. The acute neurotoxicity was checked by rotarod assay. Most of the test compounds were found effective in both seizure tests. Compound 30 (1-{4-[4-(4-chloro-phenyl)-piperazin-1-yl]-phenyl}-3-phenyl-urea) exhibited marked anticonvulsant activity in MES as well as scPTZ tests. The phase II anticonvulsant quantification study of compound 30 indicates the ED₅₀ value of 28.5 mg/kg against MES induced seizures. In addition, this compound also showed considerable protection against pilocarpine induced status epilepticus in rats. Seizures induced by 3-mercaptopropionic acid model and thiosemicarbazide were significantly attenuated by compound 30, which suggested its broad spectrum of anticonvulsant activity. Interestingly, compound 30 displayed better antidepressant activity than standard drug fluoxetine. Moreover, compound 30 appeared as a non-toxic chemical entity in sub-acute toxicity studies.