Formulation and evaluation of ketorolac tromethamine-loaded albumin microspheres for potential intramuscular administration

The objective of this work was to prepare and evaluate ketorolac tromethamine-loaded albumin microspheres using a factorial design. Albumin microspheres were prepared by emulsion cross-linking method. Selected formulations were characterized for their entrapment efficiency, particle size, surface morphology, and release behavior. Analysis of variance (ANOVA) for entrapment efficiency indicated that entrapment efficiency is best fitted to a response surface linear model. From the statistical analysis it was observed that as the drug:polymer (D∶P) ratio and volume of glutaraldehyde increased, there was a significant increase in the encapsulation efficiency. Scanning electron microscopy of the microspheres revealed a spherical, nonporous and uniform appearance, with a smooth surface. Based on the entrapment efficiency and physical appearance, 9 formulations were selected for release study. The maximum particle size observed was below 40 μm. The release pattern was biphasic, characterized by an initial burst effect followed by a slow release. All selected microspheres, except those having less polymer proportion (D∶P ratio is 1∶1), exhibited a prolonged release for almost 24 hours. On comparingr ² values for Higuchi and Peppas kinetic models, different batches of microspheres showed Fickian, non-Fickian, and diffusion kinetics. The release mechanism was regulated by D∶P ratio and amount of cross-linking agent. From the experimental data obtained with respect to particle size and extent of drug relaase, it could be concluded that the prepared microspheres are useful for once-a-day intramuscular administration of ketorolac tromethamine. Published: February 23, 2007     

Biotechnological grounds for the regulation of the component composition of cephalosporins in cultures of Acremonium chrysogenum

The dynamics of cephalosporine C and desacetylcephalosporine C alterations in cultures of Acremonium chrysogenum 309A under different conditions was studied. It was shown expedient to determine the fermantation period by the data of HPLC. Genetic predisposition of the strain used to production of both cephalosporine C and desacetylcephalosporine C is discussed. With changing the cultivation procedure, medium active acidity and cultivation time it is possible to change the biosynthesis pathway.     

The biological effects in animals in relation to the accident at the Chernobyl Atomic Electric Power Station. 9. The morphofunctional indices of the immunocompetent organs in mice]

The permanent action of small doses of low-intensity radiation on the immune status of 2.5-3.5 month CC57W mice has been investigated. Total doses of internal and external irradiation were about few cGy. The permanent action of low-level radiation on the experimental animals of the first and fourth generations was shown to change spleen and lymph nodes weights and the count of lymphocytes isolated from these organs. Cellularity and DNA synthesis in the lymph-node lymphocytes and their proliferative response to polyclonal mitogens also changed. The alterations in the parameters that characterized T-lymphocyte population were statistically significant.     

Phenomenon of hypertrophy of the testes after amputation of the lower incisors in rats]

Repeated amputation of the lower incisors in rats carried out at the early postnatal on togenesis causes an enlargement of the salivary glands and hypertrophy of the testis with the phenomena of acceleration of their differentiation. Hypertrophy of the testes withthe mentioned action was much greater (76%) than in the case of unilateral castration at the same age. In adult animals repeated amputation of the lower incisors caused hypertrophy of the salivary glands, but failed to influence the hypertrophy of the testes.     

Analysis of optimal phenotypic space using elementary modes as applied to Corynebacterium glutamicum

Background  

Quantification of the metabolic network of an organism offers insights into possible ways of developing mutant strain for better productivity of an extracellular metabolite. The first step in this quantification is the enumeration of stoichiometries of all reactions occurring in a metabolic network. The structural details of the network in combination with experimentally observed accumulation rates of external metabolites can yield flux distribution at steady state. One such methodology for quantification is the use of elementary modes, which are minimal set of enzymes connecting external metabolites. Here, we have used a linear objective function subject to elementary modes as constraint to determine the fluxes in the metabolic network of Corynebacterium glutamicum. The feasible phenotypic space was evaluated at various combinations of oxygen and ammonia uptake rates.     

Effect of carbohydrates in the culture medium on amino acid composition of a cephalosporin C producer

The intracellular and extracellular amino acid composition of an auxotrophic methionine-deficient strain of Acremonium chrysogenum was studied in respect of the content of various carbohydrates in the fermentation medium. In the presence of glucose, an intensive involvement of exogenous DL-methionine into the cell metabolism was observed at earlier stages than in the presence of dextran or succrose. The total content of intracellular amino acids was lower in the cells grown on the medium with glucose. The production of cephalosporin C depended on the intracellular content of methionine, glutamic acid and lysine.     

Effects of fluoxetine on locomotor activity: possible involvement of dopamine

Plus-maze benavior of adult mail rats was assessed and contents of 5-hydroxyindoleacetic acid (5-HIAA) and dopamine (DA) in different brain regions were analyzed after two-week fluoxetine treatment (25 mg/kg/day, per os). Chronic fluoxetine treatment produced a general decrease in the brain 5-HIAA content and a decrease in DA content in the frontal cortex and striatum. Behaviorally, fluoxetine-treated animals displayed enhanced anxiety and decreased locomotor activity. The DA depletion os supposed to be responsible for fluoxetine-produced hypolocomotion. This is supported by a significant correlation between the dopamine content in the frontal cortex and the number of entries into the closed arms of the plus-maze. The results suggest that the hypolocomotor effect of fluoxetine may involve the changes in the dopaminergic system.     

The role of the functional sites of the Merlin tumor suppressor in Drosophila spermatogenesis

The Merlin gene of Drosophila is homologous to the human Neurofibromatosis 2 (NF2) gene an important regulator of proliferation and endocytosis of cell receptors. It was earlier shown that the Thr5 residue of the Drosophila Merlin protein was homologous to Ser518 of the human protein (which was already known to undergo phosphorylation); hence, it was assumed that Thr559 of Drosophila also was a substrate of phosphorylation. The mutant Merlin proteins MerT559D (an analog of the phosphorylated form) and MerT559A (a nonphosphorylated form) were constructed and tested, under the conditions of ectopic expression for the ability to correct the spermatogenesis defects induced by the Mer4 mutation. The mutant form MerT559D was demonstrated to restore the abnormal nebenkern phenotype induced by this mutation, whereas the MerT559A substituted form did not restore this phenotype. Ectopic expression o the wild-type Merlin protein, MerT559A mutant form, and mycMer345-635 truncated protein in a normal genotype resulted in the abnormal nebenkern phenotype, whereas this phenotype was not observed in the case ofectopic expression of the MerT559D analog of the phosphorylated form. Ectopic expression of the mycMer3, mycMerABB, and mycMer-379 truncate variants led to disturbance of meiotic cytokinesis.     

A steady state analysis indicates that negative feedback regulation of PTP1B by Akt elicits bistability in insulin-stimulated GLUT4 translocation

Background  

The phenomenon of switch-like response to graded input signal is the theme involved in various signaling pathways in living systems. Positive feedback loops or double negative feedback loops embedded with nonlinearity exhibit these switch-like bistable responses. Such feedback regulations exist in insulin signaling pathway as well.