The disposition and metabolism of a hypnotic benzodiazepine, quazepam, in the hamster and mouse

The disposition of 14C-quazepam (7-chloro-(2,2,2-trifluoroethyl) [5-14C]-5-o-fluorophenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-thione), a new benzodiazepine hypnotic, was studied in hamsters and mice after iv and po dosing. In both species, quazepam was rapidly absorbed, as indicated by the plasma Cmax being reached within 1 hr of an oral dose (5 mg/kg). Also, radioactivity is essentially completely absorbed in both species, since the percentage of dose excreted in the urine was not dependent on the route of drug administration. Radioactivity was widely distributed in the tissues of both species; however, it was concentrated (relative to plasma) only in the liver and kidneys. In hamsters, 66-77% of the radioactivity was excreted within 48 hr, and 97% within 7 days of dosing (57% found in urine and 40% in feces after iv; 54% in urine and 43% in feces after po dosing). In mice, 86-88% of the radioactivity was excreted within 24 hr, and 98% within 4 days of dosing (43% in urine and 56% in feces after iv, 37% in urine and 61% in feces after po dosing). In both species, plasma levels of quazepam, measured by GLC, accounted for a very small percentage of plasma radioactivity and the elimination half-life was short (2.4 hr in hamster and 1.2 hr in mice), indicating extensive first pass metabolism for this drug. TLC analysis of plasma and urine extracts from both species showed biotransformation of quazepam involved substitution of oxygen for sulfur, followed by: (a) N-dealkylation, 3-hydroxylation, and conjugation or (b) 3-hydroxylation and conjugation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Optimization and evaluation of silk fibroin-chitosan freeze-dried porous scaffolds for cartilage tissue engineering application

Silk fibroin/chitosan blend has been reported to be an attractive biomaterial that provides a 3D porous structure with controllable pore size and mechanical property suitable for tissue engineering applications. However, there is no systematic study for optimizing the ratio of silk fibroin (SF) and chitosan (CS) which seems to influence the scaffold property to a great extent. The present research, therefore, investigates the effect of blend ratio of SF and CS on scaffold property and establishes the optimum value of blend ratio. Among the various blends, the scaffolds with blend ratio of SF/CS (80:20) were found to be superior. The scaffold possesses pore size in the range 71–210 μm and porosity of 82.2 ± 1.3%. The compressive strength of the scaffold was measured as 190 ± 0.2 kPa. The cell supportive property of the scaffold in terms of cell attachment, cell viability, and proliferation was confirmed by cell culture study using mesenchymal stem cells derived from umbilical cord blood. Furthermore, the assessment of glycosaminoglycan secretion on the scaffolds indicates its potentiality toward cartilage tissue regeneration.     

Lipopeptide with a RGDK tetrapeptide sequence can selectively target genes to proangiogenic alpha5beta1 integrin receptor and mouse tumor vasculature

Integrins, the major class of alphabeta heterodimeric transmembrane glycoprotein receptors, play crucial roles in mediating tumor angiogenesis. Genetic ablation experiments combined with use of antibodies/peptide ligands for blocking either alpha(5) or beta(1) integrins have convincingly demonstrated alpha(5)beta(1) integrin to be unquestionably proangiogenic among the 24 known integrin receptors. Herein, we report on a novel RGDK-lipopeptide 1 that targets selectively alpha(5)beta(1) integrin and is capable of targeting genes to mouse tumor vasculatures.     

Electron microscopic evaluation of bacterial adherence to polyvinyl chloride endotracheal tubes used in neonates

Studies in adults suggest a possible association between pulmonary nosocomial infection and bacterial adherence to endotracheal tubes (ETT). Some strains of coagulase-negative Staphylococcus produce a mucoid extracellular material known as slime or glycocalyx that helps bacteria adhere to the surface of biomaterials. We examined by scanning and transmission electron microscope the surface of 29 polyvinyl ETT removed from neonatal patients, and ten unused ETT. Multiple surface irregularities were found in the unused tubes. These irregularities were most prominent in the tip and around the side hole. Amorphous material containing slime-producing bacteria was found on 29 ETT removed from patients. Tubes in place for longer times had greater areas of surface covered; the amorphous material was more concentrated in the areas where surface irregularities were most prominent. No clinical correlation with pulmonary nosocomial infection was established.     

Bleomycin affects cell wall anchorage of mannoproteins in Saccharomyces cerevisiae.

Bleomycin induces strand breakage in DNA through disruption of glycosidic linkages. We investigated the ability of bleomycin to damage yeast cell walls, which are composed primarily of carbohydrate. Bleomycin treatment of intact yeast cells facilitated enzymatic conversion of yeasts to spheroplasts. Bleomycin treatment also altered anchorage of mannoproteins to the cell wall matrix in intact cells or isolated cell walls. Cell surface mannoproteins were labelled with 125I, and their solubilization was monitored. Seventeen hour treatments with bleomycin released some of the label directly into treatment supernatants and facilitated extraction of mannoproteins by dithiothreitol and lytic enzymes. Bleomycin treatments as short as 10 min caused changes in extraction of mannoproteins from intact cells. Specifically, cell wall anchorage of several mannoproteins was affected by the drug. There were drug-induced changes in extractability of mannoproteins with apparent molecular weights of 96,000, 80,000, 61,000, 41,000, 31,500, and 21,000 (determined after deglycosylation with endo-N-acetylglucosaminidase H). The similarity of results obtained in the presence and absence of cycloheximide, the appearance of cell wall effects after only 10 min of treatment, and the similarity of effects in intact cells and isolated cell walls are consistent with direct drug-induced damage and inconsistent with a mechanism dependent on expression of bleomycin-damaged genes or other intracellular mediators. The results are consistent with bleomycin-mediated increases in cell wall permeability through disruption of glycosidic cross-linking structures in the cell wall.     

A halotolerant Enterobacter sp. displaying ACC deaminase activity promotes rice seedling growth under salt stress

Agricultural productivity is proven to be hampered by the synthesis of reactive oxygen species (ROS) and production of stress-induced ethylene under salinity stress. One-aminocyclopropane-1-carboxylic acid (ACC) is the direct precursor of ethylene synthesized by plants. Bacteria possessing ACC deaminase activity can use ACC as a nitrogen source preventing ethylene production. Several salt-tolerant bacterial strains displaying ACC deaminase activity were isolated from rice fields, and their plant growth-promoting (PGP) properties were determined. Among them, strain P23, identified as an Enterobacter sp. based on phenotypic characteristics, matrix-assisted laser desorption ionization-time of flight mass spectrometry data and the 16S rDNA sequence, was selected as the best-performing isolate for several PGP traits, including phosphate solubilization, IAA production, siderophore production, HCN production, etc. Enterobacter sp. P23 was shown to promote rice seedling growth under salt stress, and this effect was correlated with a decrease in antioxidant enzymes and stress-induced ethylene. Isolation of an acdS mutant strain enabled concluding that the reduction in stress-induced ethylene content after inoculation of strain P23 was linked to ACC deaminase activity.     

Cross sectional study to evaluate microbiological spectrum of RTI/STI and co-infections among women with cervicitis or cervico-vaginitis from a community clinic in Mumbai

Cervicitis is an inflammatory condition of cervix, when presented along with vaginal discharge; it is termed as cervico-vaginitis. These can be infective, hence important to diagnose due to risk of spreading to upper genital tract. This cross-sectional study was undertaken to evaluate the microbiological spectrum in cervicitis or cervico-vaginitis among 100 sexually active women by Gram stain and Multiplex Real time polymerase chain reaction. Bacterial vaginosis 21(21%) was the most common RTI. Among STIs, genital mycoplasmas were the predominant infections hence further research is required to understand their pathogenesis.     

Albomycin is an effective antibiotic, as exemplified with Yersinia enterocolitica and Streptococcus pneumoniae

Albomycin belongs to the class of sideromycins, compounds composed of iron carriers linked to antibiotic moieties. Albomycin was found to be active against bacteria that have a functional ferric hydroxamate transport system meaning that bacteria will actively transport albomycin until they die. We examined the activity spectrum of albomycin for bacterial pathogens and found that Enterobacteriaceae except species of Proteus and Morganella were sensitive. Resistance in the two genera was due to the lack of the ferric hydroxamate transport system. Among Gram-positive bacteria, Staphylococcus aureus and Streptococcus pneumoniae were highly sensitive, whereas Streptococcus agalactiae, Streptococcus pyogenes, and Staphylococcus epidermidis were resistant. The in vivo efficacy of albomycin was examined in mice infected with S. pneumoniae or Yersinia enterocolitica. A single dose of 10mg albomycin/kg body weight reduced the colony-forming units of Y. enterocolitica by three to four orders of magnitude. A single dose of 1mg albomycin/kg body weight was sufficient to clear S. pneumoniae infections in mice. In direct competition experiments with wild-type S. pneumoniae and its albomycin-resistant mutant, the recovery rate of the mutant was lower than for the wild-type indicating that the mutant had reduced fitness in the mouse model. We conclude that albomycin is effective in clearing infections caused by both Gram-positive and Gram-negative bacteria in a mouse model. Albomycin treatment reduces the bacterial load allowing the immune system to remove residual albomycin-resistant bacteria, and as such would make albomycin-based antibiotics an adjunct to treatment. The ferrichrome transport system serves as a Trojan horse to get albomycin into bacteria.