Development of a controlled release of salicylic acid loaded stearic acid-oleic acid nanoparticles in cream for topical delivery.

Lipid nanoparticles are colloidal carrier systems that have extensively been investigated for controlled drug delivery, cosmetic and pharmaceutical applications. In this work, a cost effective stearic acid-oleic acid nanoparticles (SONs) with high loading of salicylic acid, was prepared by melt emulsification method combined with ultrasonication technique. The physicochemical properties, thermal analysis and encapsulation efficiency of SONs were studied. TEM micrographs revealed that incorporation of oleic acid induces the formation of elongated spherical particles. This observation is in agreement with particle size analysis which also showed that the mean particle size of SONs varied with the amount of OA in the mixture but with no effect on their zeta potential values. Differential scanning calorimetry analysis showed that the SONs prepared in this method have lower crystallinity as compared to pure stearic acid. Different amount of oleic acid incorporated gave different degree of perturbation to the crystalline matrix of SONs and hence resulted in lower degrees of crystallinity, thereby improving their encapsulation efficiencies. The optimized SON was further incorporated in cream and its in vitro release study showed a gradual release for 24 hours, denoting the incorporation of salicylic acid in solid matrix of SON and prolonging the in vitro release.

Angiogenic responses are enhanced in mechanically and microscopically characterized, microbial transglutaminase crosslinked collagen matrices with increased stiffness.

During angiogenesis, endothelial cells (ECs) use both soluble and insoluble cues to expand the existing vascular network to meet the changing trophic needs of the tissue. Fundamental to this expansion are physical interactions between ECs and extracellular matrix (ECM) that influence sprout migration, lumen formation and stabilization. These physical interactions suggest that ECM mechanical properties may influence sprouting ECs and, therefore, angiogenic responses. In a three-dimensional angiogenic model in which a monolayer of ECs is induced to invade an underlying collagen matrix, angiogenic responses were measured as a function of collagen matrix stiffness by inducing collagen crosslinking with microbial transglutaminase (mTG). By biaxial mechanical testing, stiffer collagen matrices were measured with both mTG treatment and incubation time. Using two-photon excited fluorescence (TPF) and second harmonic generation (SHG), it was shown that collagen TPF intensity increased with mTG treatment, and the TPF/SHG ratio correlated with biaxially tested mechanical stiffness. SHG and OCM were further used to show that other ECM physical properties such as porosity and pore size did not change with mTG treatment, thus verifying that matrix stiffness was tuned independently of matrix density. The results showed that stiffer matrices promote more angiogenic sprouts that invade deeper. No differences in lumen size were observed between control and mTG stiffened matrices, but greater remodeling was revealed in stiffer gels using SHG and OCM. The results of this study show that angiogenic responses are influenced by stiffness and suggest that ECM properties may be useful in regenerative medicine applications to engineer angiogenesis.

Memory effect of an organic based trilayer structure with Au nanocrystals in an insulating polymer matrix.

The memory effects of gold (Au) nanocrystal (NC) non-volatile memory structures consisting of polyvinylpyrrolidone (PVP) K-30 polymer tunneling and control layers are investigated. The trilayer structure (PV P/Au-NCs + PV P/PV P) on p-type Si substrate was fabricated by spin coating, and transmission electron microscopy study reveals that the average size of the Au-NCs formed is about 5 nm in diameter. Capacitance-voltage (C-V) measurement on the memory structure shows a counter-clockwise hysteresis loop with a significant flat band voltage shift, revealing a memory effect of the Au-NCs with a charge density of up to 1 x 10(12) cm(-2) and a flat band voltage shift of 2.0 V. A unique feature of the double loop in the C-V curves suggests double barriers during electron tunneling. The I-V hysteresis is also characterized, and a switching mechanism of resistive change is discussed.

Characterization of the interface between the Hf-based high-k thin film and the Si using spatially resolved electron energy-loss spectroscopy.

The interfacial structures of HfO(2) and HfAlO thin films on Si have been investigated using spatially resolved electron energy-loss spectroscopy. We have found that interfaces are not atomically sharp, and variation in the symmetry of the local atomic coordination lasts for a couple of monolayers for both the as-deposited HfO(2) and the HfAlO samples. Annealing of the HfO(2) film in the oxygen environment leads to the formation of a thick SiO(2)/SiO(x) stack layer in-between the original HfO(2) and the Si substrate. As a comparison, the interfacial stability is significantly improved by Al incorporation into the HfO(2) film (forming HfAlO), which effectively reduced/eliminated the interfacial silicon oxide formation during the oxygen annealing process. The mechanism of the high-k film/substrate stabilization by Al incorporation is discussed based on the experimental results.

Negative photoconductivity and memory effects of germanium nanocrystals embedded in HfO2 dielectric.

A metal-insulator-semiconductor (MIS) structure containing an HfO2/SiO2 stack tunnel layer, isolated Germanium (Ge) nanocrystals, and an HfO2 capping layer, was obtained by an electron-beam evaporation method. A high-resolution transmission electron microscopy (HRTEM) study revealed that uniform and pronounced Ge nanocrystals had formed after annealing. Raman spectroscopy provided evidence for the formation of Ge-Ge bonds and the optimal annealing temperature for the crystallization ratio of the Ge. The electric properties of the MIS structure were characterized by capacitance-voltage (C-V) and current-voltage (I-V) measurements at room temperature. Negative photoconductivity was observed when the structure was under a forward bias, which screened the bias voltage, resulting in a decrease in the current at a given voltage and a negative shift in flat band voltage. A relatively high stored charge density of 3.27 x 10(12) cm 2 was also achieved.

The type IV pre-pilin leader peptidase of Xanthomonas campestris pv. campestris is functional without conserved cysteine residues.

Type IV pre-pilin leader peptidase was demonstrated to be required for protein secretion, in addition to its involvement in biogenesis of type IV pIII. The type IV pre-pilin leader peptidase gene of Xanthomonas campestris pv. campestris was located on a 3 kb Accl fragment on account of its hybridization with the DNA fragment containing the type IV pre-pilin leader-peptidase gene pilD/xcpA of Pseudomonas aeruginosa. Sequencing of the cloned fragment revealed an open reading frame (ORF) (designated xpsO) of 287 amino acid residues. A protein with an apparent molecular mass of approximately 32.5 kDa was synthesized in vitro from a DNA fragment containing the xpsO gene. The amino acid sequence shares 50% identity with that of PilD throughout the entire sequence. Among other type IV pre-pilin leader peptidases, XpsO is unique in not having the two conserved -CXXC-motifs in a cytoplasmic domain. Instead, new motifs were noted when the protein was compared with XpsE, which is another member of the extracellular protein-secretion machinery. When the xpsO gene was introduced into the pilD mutant of P. aeruginosa, both the sensitivity against infection with the pilus-specific phage PO4 and the ability to secrete extracellular protein were recovered. Furthermore, immunoblot analysis indicated that the P. aeruginosa pilin was apparently processed in vivo by the xpsO gene product.

Treatment of failing glaucoma filtering cystic blebs with tissue plasminogen activator (tPA).

Tissue plasminogen activator (tPA) is a clot-specific fibrinolytic agent shown to be effective in decreasing postsurgical fibrin formation and enhancing filtration after trabeculectomy. To evaluate the efficacy of tPA on blebs showing clinical evidence of failure, a retrospective analysis was performed on 20 eyes of 20 glaucoma patients with failing or failed cystic filtering bleb treated with tPA intrableb and/or intracameral injection. The average pre-tPA intraocular pressure (IOP) was 18.0 +/- 7.2 mmHg and post-tPA was 12.9 +/- 6.2 mmHg. Fifteen of 20 eyes (75%) were able to maintain their IOP at or below target level, in the follow-up period of 3 to 7 months. Eight of the 15 eyes with successful outcome were free of glaucoma medication. Patients experienced no pain or irritation during and after the injection of tPA. No adverse effects on visual acuity or major complications were encountered. Transient mild complications related to tPA injections were subconjunctival hemorrhage (2 eyes), hyphema (1 eye) and hypotony (6 eyes). The revision of failing cystic bleb by tPA intrableb and/or intracameral injection may be considered as a useful adjunct with low risk in management of failing cystic blebs. A well designed clinical trial would provide needed information pertaining to the nature of cystic bleb formation as well as the efficacy, safety and clinical implication on the tPA treatment.

Establishment and characterization of a tumor cell line from human nasopharyngeal carcinoma tissue.

An epithelial tumor cell line, CG1, was established from human nasopharyngeal carcinoma tissues. The CG1 cells are of an epithelial origin as shown by their reactivities with the epithelial-specific antikeratin antibodies and by the presence of the desmosome structure at cell-cell junctions. CG1 cells possess characteristics of tumor cells because these cells are tumorigenic in nude mice and also have reduced serum requirements for in vitro cultivation. The doubling time of CG1 cells is 20 h and these cells have been successfully cultured in vitro for more than 200 generations. The average chromosome number of these cells is 60. Slot and Southern blot hybridizations showed the presence of Epstein-Barr virus-DNA sequences in CG1 cells. This cell line provides us an in vitro system for the study of the role of Epstein-Barr virus in nasopharyngeal carcinoma.

Efficacy and safety of once-daily levobunolol for glaucoma therapy.

We studied the ocular hypotensive efficacy and safety of 0.5% levobunolol hydrochloride and 0.5% timolol maleate administered topically once daily for 3 months in 91 patients (46 in the levobunolol group and 45 in the timolol group) with primary or secondary open-angle glaucoma or ocular hypertension. In this randomized double-masked parallel clinical study, intraocular pressure (IOP) was successfully controlled in 78% of the patients who received levobunolol and 89% of those who received timolol. The overall mean decrease in IOP was 5.6 mm Hg (decrease of 23%) in the levobunolol group and 6.7 mm Hg (26%) in the timolol group, a nonsignificant difference. In both groups the overall mean IOP during treatment was significantly lower than the pretreatment value (p less than 0.001). For both treatment groups changes in heart rate and blood pressure were minimal. We conclude that both 0.5% levobunolol and 0.5% timolol administered once daily are effective and safe in lowering IOP in most patients with ocular hypertension or open-angle glaucoma.

Effect of changing medication regimens in glaucoma patients.

When glaucoma medication fails to adequately control intraocular pressure (IOP), a second medication is frequently added. Before adding a second drug to patients whose IOP was no longer controlled by 0.5% timolol, we tested the effect of switching to another beta blocker, levobunolol (0.5 or 1%). We also evaluated the effect of study participation on compliance in the control group continuing to receive 0.5% timolol. In each treatment group, the IOP of approximately 30-40% of the patients was successfully controlled for the 3-month study period. The remaining patients did not exhibit significant pressure reductions and were dropped from the study within 2 weeks. We concluded that (1) the results of 'switch' studies without a control group must be interpreted carefully, and (2) the initiation of a 'new regimen' with an equieffective beta blocker may be sufficient to increase compliance and thereby control IOP.

The effect of different brands of MacConkey and xylose lysine deoxycholate agar on the isolation of Aeromonas hydrophila.

Aeromonas hydrophila has been reported to be involved in the opportunistic infection of human beings, therefore, its rapid diagnosis from the clinical specimens was considered to be extremely important for the prognosis. The effect of different brands of MacConkey (MAC) and xylose lysine deoxycholate (XLD) agars on the plating efficiency and colony size of A. hydrophila was evaluated by comparing with blood agar. Results indicate that (i) except Eiken's MAC have low plating efficiency, all the MAC from BBL, Difco, Mast, Merck, and Gibco have good plating efficiency; (ii) except Eiken's and Gibco XLD, all XLD from Difco, Mast, and Merck have larger bacterial colony size; and (iii) colonies of A. hydrophila appeared on MAC are larger than those on XLD of the same brands. We suggested that a clinical laboratory microbiologist should be alert in selecting the appropriate media to isolate the clinically important bacteria.

Factors affecting ascorbate oxidation in aqueous humor.

Aqueous humor from human glaucomatous eyes was divided into two groups. Group I aqueous humor contains a negligible amount of ascorbate, while group II contains ascorbate. Group I aqueous humor stimulates ascorbate oxidation. This oxidative effect is inhibited by the addition of EDTA, indicating the presence of metallic ions. The amount of copper determined by atomic spectrophotometry in these samples was 1.54 micrograms/ml. On the contrary, group II aqueous humor protects against ascorbate oxidation. The small amount of albumin present in these samples accounts for part of this protective effect.

The significance of normal angle vessels.

One hundred patients (200 eyes) were examined over a one-year period for the presence of normal anterior chamber angle vessels. Normal vessels were observed in the angle in 21% of eyes examined. The types, location, and number of normal vessels are documented. The significance of these vessels in two eyes with anterior chamber angle fixated lenses is discussed.

Midazolam as induction agent prior to inhalational anaesthesia: a comparison with thiopentone.

Midazolam, a new water-soluble benzodiazepine, was compared with thiopentone as an induction agent prior to inhalational anaesthesia. Induction time, cardiovascular response and venous sequelae were studied in 100 healthy in-patients randomly divided into two groups. Midazolam proved to be a good alternative to thiopentone, the longer induction time being compensated by a lower incidence and duration of apnoea.

The significance of disc hemorrhage in open-angle glaucoma.

Thirty eyes of 25 patients with open-angle glaucoma and disc splinter hemorrhage (20 with unilateral and five with bilateral hemorrhage) were studied as to the extent of the visual field loss in relation to the time of onset and location of the disc hemorrhage. The degree of visual field deterioration over a follow-up period of one month to seven years was found to be higher in eyes with disc hemorrhage when compared to the contralateral eyes without disc hemorrhage of patients with bilateral open angle glaucoma.

Goniophotocoagulation in the management of rubeosis iridis.

Laser goniophotocoagulation (LGP) in the management of rubeosis iridis has been the subject of a prospective clinical trial in 12 patients over a period of four years. It is effective in the early stage of rubeosis iridis, even prior to the onset of open-angle glaucoma. Preliminary results are encouraging but only partially successful. LGP is an investigational procedure that must be employed with care. The status or characterization of the rubeosis iridis requires detailed description of at least four clinical stages to evaluate the LGP usefulness.

The effect of optic nerve transection upon the hypotensive action of ascorbate and mannitol.

Some investigators have suggested that osmolarity agents act on a central neural regulation mechanism rather than producing a direct local effect on the ocular hemodynamics. In this study, a small dose of ascorbate (.15 gm/kg, IV injection) was given to rabbits following unilateral optic nerve transection. The intraocular pressure of both eyes was significantly reduced within 5 minutes with a maximum drop at 10 minutes. When mannitol was given (0.3 gm/kg, intravenous infusion), maximal reduction of intraocular pressure occurred at 30 to 50 minutes in both eyes. In this study, it appears that optic nerve transection did not abolish the ocular response to the hypotensive action of either ascorbate or mannitol. On the contrary, the hypotensive effect of ascorbate was stronger in the experimental eye. The effective time on aqueous humor dynamics of the ascorbate occurred earlier than that of mannitol under similar experimental situations.