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The objective of this study was to prepare NS-chitosan microparticles for the delivery of 5-aminosalicylic acid (5-ASA) to the colon. Microparticles can spread out over a large area of colon allowing a more effective local efficacy of 5-ASA. N-Succinyl-chitosan was chosen as carrier system because of its excellent pharmaceutical properties in colon drug targeting such as poor solubility in acid environment, biocompatibility, mucoadhesive properties, and low toxicity. It was prepared by introducing succinic group into chitosan N-terminals of the glucosamine units. 5-ASA loaded NS-chitosan microparticles were prepared using spray-drying. As a control, a matrix obtained by freeze-drying technique was also prepared and tested. Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC) and X-ray diffraction studies show the 5-ASA/NS-chitosan electrostatic interactions in both the systems. Mean size of the microparticles was around 5 μm, zeta potential value of both systems was always negative. Scanning electron microscopy (SEM) images show an acceptable spherical non porous structure of microparticles. In vitro swelling and drug release studies were in accordance with the polymer properties, showing the highest swelling ratio and drug release at pH=7.4 (colonic pH) where microparticles were able to deliver more than 90% of 5-ASA during 24h experiments. Rheological studies are in accordance with the swelling and release studies., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The aim of this work was to develop new microparticles for drug delivery to lungs by coating liposomes with chitosan (CH)-xanthan gum (XG) polyelectrolyte complexes to obtain chitosomes. To this purpose, two groups of liposomes were prepared using a mixture of soy phosphatidylcholine and hydrogenated soy phosphatidylcholine in two different concentrations to evaluate their capability to entrap appropriate amounts of the model drug rifampicin. The obtained vesicles were then coated with different CH-XG weight ratios and liposomes and chitosomes were characterized in terms of morphology, size, size distribution, zeta potential, drug entrapment, and rheological properties. The efficiency of chitosomes and liposomes during nebulization was also studied. Results of this study indicated that nebulization and rheological properties of chitosomes are affected by the CH-XG weight ratio. In particular, CH-XG 1:0.5 (w/w) coating was able to greatly improve drug total mass output and drug deposition in the lower stages of the impinger., (Copyright © 2011 Wiley Periodicals, Inc.)

In the roundtable that follows, clinicians discuss a study published in this issue of the Journal in light of its methodology, relevance to practice, and implications for future research., (Copyright © 2010 Mosby, Inc. All rights reserved.)

Recently three groups of rifampicin (RIF)-loaded microparticles (MPs), consisting of chitosan (CHT), PLGA and PLGA/CHT mixtures, were assessed in terms of RIF-loading and retention during nebulisation. The CHT-coated PLGA MPs were found to exhibit high RIF-loading ability together with nebulisation ability, stability, and mucoadhesive properties. All MP types had comparable toxicity towards alveolar cells which was significantly lower than that of the free drug. Herein, we study the release of RIF from all MP-types, during incubation in buffer with pH values: 4.40 and 7.40. Results show that CHT particles exhibit a higher burst release compared to PLGA MPs; at pH 4.40, which is explained by the higher solubility of CHT in acidic media. At pH 7.40 burst release from CHT MP's is significantly lower when CHT is crosslinked with glutaraldehyde, which is consistent with their - previously observed - increased stability during nebulization. From PLGA MPs, RIF release was pH independent under the conditions applied, while the amount of PVA (stabilizer) considerably affected drug release. When PLGA MP's were coated with CHT, at pH 7.40 the retention of RIF increased further (compared to non-coated MPs), while at pH 4.40 the release was faster from the CHT-coated particles. Concluding, it is proven that when PLGA MPs are coated with CHT, in addition to increased particle mucoadhesive properties, the release kinetics of RIF are modified.

The chemical composition of the essential oil and methanol extract of Calycotome villosa (Poiret) Link leaves collected in Sardinia (Italy) has been studied by analytical and spectroscopic methods. Falcarinol and some alcohols, terpenes, furan derivatives, and paraffins have been isolated from the essential oil. Thirteen alkaloids and falcarinol have been identified in the chloroform fraction of the basic methanol extract. Six flavonoids and four anthraquinones have been isolated in the chloroform fraction after acidification of the basic methanol extract. The cytotoxic and antimicrobial activities have also been evaluated. The essential oil, the methanol extract in toto, and the fraction of the basic extract showed strong cytotoxicity, whereas the fraction of the acid extract showed lower cytotoxicity. Furthermore, this fraction showed good antibacterial activity against Staphylococcus aureus, Bacillus lentus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Providencia rettgeri, and Morganella morganii. It can therefore be stated that this plant's cytotoxicity is prevalently due to falcarinol.

The essential oil obtained in toto from Santolina insularis was investigated for its antiviral activity on herpes simplex type 1 (HSV-1) and type 2 (HSV-2) in vitro. The IC(50) values, determined by plaque reduction assays, were 0.88 and 0.7 microg/ml for HSV-1 and HSV-2, respectively, while the CC(50) determined by the MTT test on Vero cells was 112 microg/ml, indicating a CC(50)/IC(50) ratio of 127 for HSV-1 and 160 for HSV-2. Results obtained by plaque reduction assays also indicated that the antiviral activity of S. insularis was principally due to direct virucidal effects. Antiviral activity against HSV-1 and HSV-2 was not observed in a post-attachment assay, and attachment assays indicated that virus adsorption was not inhibited. Up to 80% inhibition of HSV-1 was achieved at the concentration of 40 microg/ml by yield reduction assay. Furthermore, reduction of plaque formation assays also showed that S. insularis essential oil inhibits cell-to-cell transmission of both HSV-1 and HSV-2.

This report sums up the research work since 1993 on the synthesis of coumarin derivatives using carbon suboxide as reagent.

Some coumarin 7-substituted cephalosporins and related sulfones were prepared and an antimicrobial assay was performed. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) carried out on cephalosporins showed a potential activity of some of the synthesized compounds against Gram-positive microorganisms. The tests performed on the corresponding sulfones showed no significant activity, neither as antimicrobial agents nor as inhibitors of beta-lactamase. An association of sulfone 6a with ampicillin was observed to inhibit Gram-positive microorganisms with a lower MIC than for ampicillin alone.

The synthesis of (N-substituted)amino-spiroalkan-dione derivatives 3 is described starting from enamines 1 and carbon suboxide 2, and their inhibitory effects on blood coagulation in vivo and on platelet aggregation in vitro are determined. Some of synthesized compounds showed a strong anticoagulant activity. A comparative pharmacological study of the anticoagulant effects of the new compounds versus Warfarin suggests that their behaviour is analogous, though the action mechanism is different.

The synthesis of N-substituted-2-oxo-(2H)1-Benzopyran-3-Carboxamide derivatives starting from semicarbazones or thiosemicarbazones and Carbon Suboxide (ratio 1:2) is described. Some compounds showed an interesting analgesic and/or diuretic activity in mice.

Many investigators are now using stable isotopes in place of radioactive isotopes because of ethical considerations in human research. Our laboratory has had a long history in the development of an ovine model for the study of the physiological and biochemical changes during pregnancy. We wanted to extend some of the hypotheses and experimental protocols developed while using this model system to the human. As a first step in this process, we carried out infusions using a mixture of both 14C and 13C isotopes of the essential amino acid L-leucine. Results from this study showed that turn-over rates calculated using the two isotopes were equal within experimental error (8.99 +/- 0.45 and 8.97 +/- 0.52 mumol/kg.min, respectively). A key step in the development of the techniques for this study involved the use of tert.-butyldimethylsilyl derivatives for the amino acids. Because of the strong M-57 peak seen in the mass spectra of these compounds, we were able to use a relatively inexpensive Hewlett-Packard mass-selective detector for these determinations. Enrichments in triplicate measurements of the same sample had a precision of +/- 0.03%. Similar precision data were obtained in enrichment measurements of the keto acids derived from the amino acids. The combination of the speed of the analysis and the excellent precision have provided us with the opportunity to study uptake and loss across an organ system (i.e. placenta, liver, etc). This tool is now being used to study the detailed flow of amino acids across the placenta during both normal and abnormal pregnancies.

The synthesis of 2,4-dione derivatives of 1,5-benzodithiepine, 1,5-benzodiazepine and 1,5-benzothiazepine and the anti-microbial activity in vitro of these derivatives and of analogous of 1,5-benzodioxepine, 1,5-benzoxathiepine and 1,5-benzoxazepine, previously prepared, are reported. Some of these compounds showed a good activity against some Gram positive microorganisms and blastomycetes.

Tracer methods using both carbon-13 and -14 have been utilized for determination of ovine fetal amino acid disposal and the results compared in seven animals. We infused [1-13C]leucine simultaneously with [1-14C]leucine into the fetal circulation of pregnant sheep chronically catheterized during late gestation. Radioactive and stable isotope enrichments of leucine (Leu) and stable isotope enrichments of ketoisocaproic acid (KIC) in the umbilical artery and vein and the maternal artery and uterine vein were measured. Stable isotope enrichments and concentrations of both Leu and KIC were determined from a single 0.2-ml sample by the use of internal standards and electron ionization GC/MS analysis after a simple isolation and derivatization procedure. The KIC/Leu enrichment ratio was measured for the first time in fetal arterial plasma and was 0.66 +/- 0.05 (SE). Fetal leucine disposal rate was 9.0 +/- 0.5 (SE) micron/min/kg. Disposal rates determined by stable isotopes were not different from those determined by radioactive isotopes. The GC/MS stable isotope method provided higher precision in both leucine concentration and enrichment measurements and has been shown to be a general method for the determination of concentration and isotopic enrichment of other amino acids and their corresponding keto acids. Furthermore, this method is ideally suited to clinical studies where large numbers of samples of rather small volume can easily be studied with a short turnaround time.

A photoelectric plethysmographic probe, which emits and receives a low-voltage infrared light was placed in the vaginal apex of 122 high-risk pregnant women. The normal pulse form of the upper vagina does not have a diastolic notch. A study was undertaken to determine whether the vaginal apex pulse recording equals the accuracy, sensitivity, and specificity of the uterine artery Doppler velocimetry, and whether abnormal uterine artery wave forms are fixed. The vaginal apex recordings had greater sensitivity to abnormal outcome than did the uterine artery Doppler technique. The vaginal apex pulse height decreased significantly in a majority of the women undergoing elective cesarean section and during uterine contractions. In patients with abnormal wave forms (diastolic notches) and treated with either terbutaline sulfate or magnesium sulfate, the diastolic notch disappeared in eight out of 14 cases.