The development of a febrile response to pyrogen in the thyroid-deficient rabbit

The development of the febrile response to E. coli lipopolysaccharide (1.5 μg/kg, i.v.) in thyroid-deficient rabbits has been studied. Twenty-eight New Zealand White rabbits weighing 2.1-2.3 kg were used. Hypothyroidism was induced by treatment with propylthiouracil (100 or 200 mg/kg body wt./15 days). Thyroid-deficient animals showed a reduction in the febrile response to lipopolysaccharide, but the effect was significantly different (p<0.01) from the control only for rabbits treated with 200 mg/kg of propylthiouracil. Propranolol (2 mg/kg, i.p.) given 30 min before lipopolysaccharide also reduced (p<0.01) the fever response in control rabbits. The results of this experiment are consistent with the hypothesis that the reduction in the febrile response of thyroid-deficient rabbits is due to the reduced number of β-adrenergic receptors, or to a change in the availability of neurotransmitter in thermogenically active tissues, such as brown fat.

Effects of antithyroid drug on the rectal temperature and metabolic parameters of ducks (Cairina moschata).

The effect of propylthiouracil oral treatment (400 mg/day per bird for 20 days) on body and thyroid weight, rectal temperature and plasma metabolic parameters of ducks (Cairina moschata) was determined. Propylthiouracil treatment produced a reduction (P less than .01) in body weight and an increase (P less than .01) in thyroid weight. The antithyroid drug also produced a decrease in rectal temperature starting from the 15th day of treatment, but did not significantly change blood glucose. Plasma free fatty acids and cholesterol concentrations progressively increased from the 5th and 10th day, respectively, in treated animals.

Effect of isotretinoin on tooth germ and palate development in mouse embryos.

Vitamin A and its derivatives, retinoic acid, tretinoin and isotretinoin, are currently used in dermatological treatments. The administration of high doses of this vitamin provokes congenital malformations in mice: cleft palate, maxillary and mandibular hypoplasia and total or partial fusion of the maxillary incisors. This study compares the tooth germs of the first maxillary and mandibular molars of fetal mice submitted to isotretinoin during organogenesis. Twelve 60-day-old female Mus musculus were divided into two groups on the 7th day of pregnancy: treated group--1 mg isotretinoin per kg body weight, dissolved in vegetable oil, was administered from the 7th to the 13th day of pregnancy; control group--vegetable oil in equivalent volume was administered orally for the same period. On the 16th day of pregnancy, the females were sacrificed, the fetuses were removed and their heads amputated. After standard laboratory procedures, 6-micron thick serial slices were stained with hematoxylin and eosin for optical microscopy examination. The results showed that both groups had closed palates with no reminiscence of epithelial cells; however, the first molar germs of the isotretinoin-treated animals showed delayed development compared to the control animals.

Cell nucleus activity during post-embryonic development of Apis melliferaL. (Hymenoptera: Apidae). Intranuclear acid phosphatase

We report nuclear acid phosphatase activity in the somatic (intra-ovariolar and stromatic) and germ cells of differentiating honey bee worker ovaries, as well as in the midgut cells of metamorphosing bees. There was heterogeneity in the intensity and distribution of electron dense deposits of lead phosphate, indicative of acid phosphatase activity in the nuclei of these tissues, during different phases of post-embryonic bee development. This heterogeneity was interpreted as a variation of the nuclear functional state, related to the cell functions in these tissues.

Development and validation of an UV spectrophotometric method for determination of gatifloxacin in tablets

A simple, sensitive and accurate spectrophotometric method was developed for the assay of gatifloxacin in raw material and tablets. Validation of the method yielded good results concerning range, linearity, precision and accuracy. The absorbance was measured at 287 nm for gatifloxacin tablet solutions. The linearity range was found to be 4.0-14.0 μg/mL for gatifloxacin. It was also found that the excipients in the commercial tablets did not interfere with the method.

Ethylcelullose microspheres containing sodium diclofenac: Development and characterization

The objective of the present study was the development and characterization of ethylcellulose microspheres containing diclofenac and the determination of the in vitro drug release profile. Microspheres were prepared by emulsification/solvent evaporation method using ethyl acetate as solvent for the polymer and water as non solvent. The microspheres were characterized by morphologic and granulometric analyses. The amount of encapsulated drug as well as its release profile in vitro were also determined. The product obtained was microparticles with smooth surface and narrow size distribution, about 50% of the particles being smaller than 5 μm. The methodology used allowed drug encapsulation with a good yield and the system provided a controlled release of diclofenac.

Liposomes and micro/nanoparticles as colloidal carriers for nasal drug delivery

The use of the nasal route for drug delivery has attracted much interest in recent years in the pharmaceutical field. Local and principally systemic drug delivery can be achieved by this route of administration. But the nasal route of delivery is not applicable to all drugs. Polar drugs and some macromolecules are not absorbed in sufficient concentration due to poor membrane permeability, rapid clearance and enzymatic degradation into the nasal cavity. Thus, alternative means that help overcome these nasal barriers are currently in development. Absorption enhancers such as phospholipids and surfactants are constantly used, but care must be taken in relation to their concentration. Drug delivery systems including liposomes, cyclodextrins, micro- and nanoparticles are being investigated to increase the bioavailability of drugs delivered intranasally. This review article discusses recent progress and specific development issues relating to colloidal drug delivery systems in nasal drug delivery. © 2006 Bentham Science Publishers Ltd.

Development and validation of HPLC method for quantitative analysis of triamcinolone in biodegradable microparticles

A simple, rapid, selective and specific high performance liquid chromatographic (HPLC) method for quantitative analysis of the triamcinolone in polylactide-co-glycolide acid (PLGA) microparticles was developed. The chromatographic parameters were reversed-phase C18 column, 250mm x 4.6mm, with particle size 5 μm. The column oven was thermostated at 35°C ± 2°C. The mobile phase was methanol/water 45:55 (v/v) and elution was isocratic at a flow-rate of 1 mL.mL-1. The determinations were performed using a UV-Vis detector at 239 nm. The injected sample volume was 10 μL. The standard curve was linear (r2 > 0.999) in the concentration range 100-2500 ng.mL-1. The method showed adequate precision, with a relative standard deviation (RSD) was smaller than 3%. The accuracy was analyzed by adding a standard drug and good recovery values were obtained for all drug concentrations used. The method showed specificity and selectivity with linearity in the working range and good precision and accuracy, making it very suitable for quantitation of triamcinolone in PLGA microparticles.

Amphibian secretions for drug discovery studies: A search for new antiparasitic and antifungal compounds

The antiparasitic and antifungal activities of nine amphibian skin secretions were studied in different in vitro models. Seven secretions presented a considerable antiprotozoan activity and one showed promising results against Candida sp. These results can be the basis for the development of new drugs, especially for neglected parasitic diseases. © 2007 Bentham Science Publishers Ltd.

The inhibition of 5-enolpyruvylshikimate-3-phosphate synthase as a model for development of novel antimicrobials

EPSP synthase (EPSPS) is an essential enzyme in the shikimate pathway, transferring the enolpyruvyl group of phosphoenolpyruvate to shikimate-3-phosphate to form 5-enolpyruvyl-3-shikimate phosphate and inorganic phosphate. This enzyme is composed of two domains, which are formed by three copies of βαβαββ-folding units; in between there are two crossover chain segments hinging the nearly topologically symmetrical domains together and allowing conformational changes necessary for substrate conversion. The reaction is ordered with shikimate-3-phosphate binding first, followed by phosphoenolpyruvate, and then by the subsequent release of phosphate and EPSP. N-[phosphomethyl]glycine (glyphosate) is the commercial inhibitor of this enzyme. Apparently, the binding of shikimate-3-phosphate is necessary for glyphosate binding, since it induces the closure of the two domains to form the active site in the interdomain cleft. However, it is somehow controversial whether binding of shikimate-3-phosphate alone is enough to induce the complete conversion to the closed state. The phosphoenolpyruvate binding site seems to be located mainly on the C-terminal domain, while the binding site of shikimate-3-phosphate is located primarily in the N-terminal domain residues. However, recent results demonstrate that the active site of the enzyme undergoes structural changes upon inhibitor binding on a scale that cannot be predicted by conventional computational methods. Studies of molecular docking based on the interaction of known EPSPS structures with (R)- phosphonate TI analogue reveal that more experimental data on the structure and dynamics of various EPSPS-ligand complexes are needed to more effectively apply structure-based drug design of this enzyme in the future. © 2007 Bentham Science Publishers Ltd.

Role of annexin 1 gene expression in mouse craniofacial bone development

BACKGROUND: Annexin 1 is a 37-kDa protein that has complex intra- and extracellular effects. To discover whether the absence of this protein alters bone development, we monitored this event in the annexin-A1 null mice in comparison with littermate wild-type controls. METHODS: Radiographic and densitometry methods were used for the assessment of bone in annexin-A1 null mice at a gross level. We used whole-skeleton staining, histological analysis, and Western blotting techniques to monitor changes at the tissue and cellular levels. RESULTS: There were no gross differences in the appendicular skeleton between the genotypes, but an anomalous development of the skull was observed in the annexin-A1 null mice. This was characterized in the newborn annexin-A1 null animals by a delayed intramembranous ossification of the skull, incomplete fusion of the interfrontal suture and palatine bone, and the presence of an abnormal suture structure. The annexin-A1 gene was shown to be active in osteocytes during this phase and COX-2 was abundantly expressed in cartilage and bone taken from annexin-A1 null mice. CONCLUSIONS: Expression of the annexin-A1 gene is important for the normal development of the skull in mice, possibly through the regulation of osteoblast differentiation and a secondary effect on the expression of components of the cPLA2-COX-2 system. © 2007 Wiley-Liss, Inc.

Molecular hybridization: A useful tool in the design of new drug prototypes

Molecular hybridization is a new concept in drug design and development based on the combination of pharmacophoric moieties of different bioactive substances to produce a new hyrid compound with improved affinity and efficacy, when compared to the parent drugs. Additionally, this strategy can results in compounds presenting modified selectivity profile, different and/or dual modes of action and reduced undesired side effects. So, in this described several example of different strategies for drug design, discovery and pharmacomodulation focused on new innovative hybrid compounds presenting analgesic, anti-inflammatory, platelet anti-aggregating, anti-infections, anticancer, cardio- and neuroactive properties.

Sustainable development: changing production patterns, social equity and the environment

Includes bibliography

Advances in sickle cell disease treatment: From drug discovery until the patient monitoring

Sickle Cell Disease (SCD) is one of the most prevalent hematological diseases in the world. Despite the immense progress in molecular knowledge about SCD in last years few therapeutical sources are currently available. Nowadays the treatment is performed mainly with drugs such as hydroxyurea or other fetal hemoglobin inducers and chelating agents. This review summarizes current knowledge about the treatment and the advancements in drug design in order to discover more effective and safe drugs. Patient monitoring methods in SCD are also discussed. © 2011 Bentham Science Publishers Ltd.

Development and validation of a microbiological agar assay for determination of orbifloxacin in pharmaceutical preparations

Orbifloxacin is a fluoroquinolone with broad-spectrum antimicrobial activity, and belongs to the third generation of quinolones. Regarding the quality control of medicines, a validated microbiological assay for determination of orbifloxacin in pharmaceutical formulations has not as yet been reported. For this purpose, this paper reports the development and validation of a simple, sensitive, accurate and reproducible agar diffusion method to quantify orbifloxacin in tablet formulations. The assay is based on the inhibitory effect of orbifloxacin upon the strain of Staphylococcus aureus ATCC 25923 used as test microorganism. The results were treated statistically by analysis of variance and were found to be linear (r = 0.9992) in the selected range of 16.0-64.0 μg/mL, precise with relative standard deviation (RSD) of repeatability intraday = 2.88%, intermediate precision RSD = 3.33%, and accurate (100.31%). The results demonstrated the validity of the proposed bioassay, which allows reliable orbifloxacin quantitation in pharmaceutical samples and therefore can be used as a useful alternative methodology for the routine quality control of this medicine. © 2011 by the authors; licensee MDPI, Basel, Switzerland.