Pharmacology of Acorus calamus L

Water soluble dried powder of alcoholic extract of roots and rhizomes of A. calamus L. was used. The in vivo experiments involved strychnine convulsant activity in frogs, spontaneous motor activity and amphetamine hyperactivity in mice, pentobarbitone sleeping-time in rats and local anaesthetic activity in guinea pigs and rabbits. Frog skeletal muscle and heart preparations and rat phrenic nerve diaphragm constituted the in vitro experiments. Plant extracts at 10, 20 mg/kg ip did not afford protection to strychnine (1,5,2.5 mg/kg) induced convulsions and same effect was found on acetylcholine induced contractions of rectus muscle except that it inhibited caffeine citrate contractions in frog. At 1, 10 and 100 micrograms/ml doses, it caused negative iono- and chronotropic effects in frogs. Dosages of 10, 25, 50 mg/kg ip of herbal extract antagonize spontaneous motor activity and also amphetamine induced hyperactivity in mice. It was less potent than chloropromazine, though exerts sedative and tranquilizing action. Local anaesthetic activity was found to be absent at 0.5 and 1% dose levels.     

Phenotypic expression of Kluyveromyces lactis killer toxin against Saccharomyces spp.

The secretion of killer toxins by some strains of yeasts is a phenomenon of significant industrial importance. The activity of a recently discovered Kluyveromyces lactis killer strain against a sensitive Saccharomyces cerevisiae strain was determined on peptone-yeast extract-nutrient agar plates containing as the carbon source glucose, fructose, galactose, maltose, or glycerol at pH 4.5 or 6.5. Enhanced activity (50 to 90% increase) was found at pH 6.5, particularly on the plates containing galactose, maltose, or glycerol, although production of the toxin in liquid medium was not significantly different with either glucose or galactose as the carbon source. Results indicated that the action of the K. lactis toxin was not mediated by catabolite repression in the sensitive strain. Sensitivities of different haploid and polyploid Saccharomyces yeasts to the two different killer yeasts S. cerevisiae (RNA-plasmid-coded toxin) and K. lactis (DNA-plasmid-coded toxin) were tested. Three industrial polyploid yeasts sensitive to the S. cerevisiae killer yeast were resistant to the K. lactis killer yeast. The S. cerevisiae killer strain itself, however, was sensitive to the K. lactis killer yeast.     

Purification and Production of Novel Angiotensin I-Converting Enzyme (ACE) Inhibitory Bioactive Peptides Derived from Fermented Goat Milk

International Journal of Peptide Research and Therapeutics - In the study, five different Lactobacillus cultures i.e. L. rhamnosus (NK2) (KR080695), L. casei (NK9) (KR732325), L. fermentum (M5)...     

In-vitro biological evaluation of some ONS and NS donor Schiff's bases and their metal complexes

Complexes of Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) with the Schiff bases salicylidene-o-aminothiophenol (H₂L) and thiophene-o-carboxaldeneaniline (SB) have been synthesized and characterized by elemental analyses, magnetic measurements, thermogravimetric analyses as well as infrared spectra and reflectance spectra. The nature of the bonding has been discussed on the basis of IR spectral data. Magnetic susceptibility measurements and electronic spectral data suggest a six-coordinated octahedral structure for these complexes. The complexes of Mn(II), Co(II), Ni(II), Cu(II) are paramagnetic, while Zn(II) and Cd(II) are diamagnetic in nature. The complexes were tested for their antimicrobial activities against Salmonella typhi, Escherichia coli and Serratia marcescens using the “Disc Diffusion Method”. The results are compared with the standard drug (tetracycline) and show moderate activity.     

Phenotypic Switching Induced by Damaged Matrix Is Associated with DNA Methyltransferase 3A (DNMT3A) Activity and Nuclear Localization in Smooth Muscle Cells (SMC)

Extracellular matrix changes are often crucial inciting events for fibroproliferative disease. Epigenetic changes, specifically DNA methylation, are critical factors underlying differentiated phenotypes. We examined the dependency of matrix-induced fibroproliferation and SMC phenotype on DNA methyltransferases. The cooperativity of matrix with growth factors, cell density and hypoxia was also examined. Primary rat visceral SMC of early passage (0–2) were plated on native collagen or damaged/heat-denatured collagen. Hypoxia was induced with 3% O₂ (balanced 5% CO₂ and 95% N₂) over 48 hours. Inhibitors were applied 2–3 hours after cells were plated on matrix, or immediately before hypoxia. Cells were fixed and stained for DNMT3A and smooth muscle actin (SMA) or smooth muscle myosin heavy chain. Illumina 450 K array of CpG sites was performed on bisulfite-converted DNA from smooth muscle cells on damaged matrix vs native collagen. Matrix exquisitely regulates DNMT3A localization and expression, and influences differentiation in SMCs exposed to denatured matrix +/− hypoxia. Analysis of DNA methylation signatures showed that Matrix caused significant DNA methylation alterations in a discrete number of CpG sites proximal to genes related to SMC differentiation. Matrix has a profound effect on the regulation of SMC phenotype, which is associated with altered expression, localization of DNMTs and discrete changes DNA methylation.     

The discovery of the benzazepine class of histamine H3 receptor antagonists

This Letter describes the discovery of a novel series of H₃ receptor antagonists. The initial medicinal chemistry strategy focused on deconstructing and simplifying an early screening hit which rapidly led to the discovery of a novel series of H₃ receptor antagonists based on the benzazepine core. Employing an H₃ driven pharmacodynamic model, the series was then further optimised through to a lead compound that showed robust in vivo functional activity and possessed overall excellent developability properties.     

Quantitative assessment of osseous, ocular, and periocular changes after hypertelorism surgery

The purpose of this study was to develop a methodology to quantify osseous, ocular, and periocular fat changes caused by correction of orbital hypertelorism to test the hypothesis that there is a quantitatively predictable relationship between the movement of the osseous orbit and that of the ocular globe. A retrospective review was performed of 10 patients who were status post unilateral or bilateral transcranial medial orbital translocation, for whom there were archival digital data for preoperative and postoperative (mean interval = 30 months) three-dimensional computed tomographic (CT) scans. In addition to standard demographic and surgical data, the clinical preoperative and postoperative interpupillary and intermedial canthal distances were recorded. By using a computer graphics workstation, the CT digital data were registered to four surgically unaltered anatomic fiducial points to allow longitudinal quantitative comparisons. The following three-dimensional measurements were made for each patient preoperatively and postoperatively: interdacryon and interocular centroid distances, and on a standard series of three horizontal and two vertical planes, the position of the medial and lateral orbital walls, and the thickness of the medial and lateral periorbital fat (20 orbits). CT digital distances were compared with similar clinical distances when possible. The age at operation ranged from 4.0 to 12.5 years (mean, 6.6 years). The reduction in interdacryon distance exceeded the reduction in intercentroid distance (mean interdacryon change = -5.3 mm versus mean intercentroid change = -2.7 mm). Although there was a strong correlation between the amount of reduction of the lateral orbital wall and intercentroid distances, there was only a moderate correlation between the reduction in the intercentroid distance and that of the medial orbital wall. Similarly, there was a moderate correlation between the decrease in thickness of the lateral periorbital fat and the reduction of intercentroid distance but not of the medial orbital fat. In conclusion, medial translocation of the orbit does not produce equivalent movement of the ocular globe; neither the intermedial canthal nor the interdacryon distance is a useful predictor of ocular centroid position; and if the goal of hypertelorism operation is reduction of interocular distance, then CT measurement of globe intercentroid distance is essential for outcome assessment.