Synthesis of N6-Substituted 9-[3-(Phosphonomethoxy)Propyl]Adenine Derivatives As Possible Antiviral Agents

A number of N ⁶ -substituted 9-[3-(phosphonomethoxy)propyl]adenine derivatives having hydroxymethyl at C-1′-position were prepared from the appropriate 6-chloroadenine derivative. The syntheses of the corresponding prodrugs of these compounds are also reported. These compounds showed poor activity against HCV in replicon assay.     

Synthesis and Characterization of New Lutidinium Ionic Liquid-Supported Vanadylsalicylaldoxime Complex for Catalytic Application in Epoxidation Reaction

A new chelating task-specific ionic liquid (TSIL), lutidinium-based salicylaldoxime ( LSOH ), and its square pyramidal vanadyl(II) complex (VO(LSO)₂) have been successfully synthesized and structurally characterized using elemental (CHN), spectral, and thermal analyses. The catalytic activity of the lutidinium-salicylaldoxime complex (VO(LSO)₂) in the alkene epoxidation reactions was studied under various reaction conditions, such as solvent effect, alkene/oxidant molar ratio, pH, reaction temperature, reaction time, and the catalyst dose. The results demonstrated that the CHCl₃ solvent, 1 : 3 of the cyclohexene/H₂O₂ ratio, pH 8, temperature of 340 K, and catalyst dose of 0.012 mmol are assigned as the optimum conditions for achieving maximum catalytic activity for VO(LSO)₂. Moreover, the VO(LSO)₂ complex has the potential for application in the effective and selective epoxidation of alkenes. Notably, under optimal VO(LSO)₂ conditions, cyclic alkenes convert more efficiently to their corresponding epoxides than linear alkenes.     

Up-regulation of neuropeptide Y Y4 receptor mRNA expression in the brainstem of refed rats following 48 h of food deprivation: effect of leptin

Neuropeptide Y (NPY) Y4 receptor (Y4R) in rat brainstem has been implicated in the signaling of satiety. In this study, we investigated the effects of leptin, and refeeding-induced satiety on Y4R mRNA expression in rat brainstem. Y4R receptor-specific primers were used to amplify the mRNA obtained from hypothalamus and brainstem utilizing conventional RT-PCR and quantitative real-time RT-PCR. No PCR product for Y4R was obtained from entire hypothalamic mRNA. Real-time RT-PCR showed a significant two-fold increase in the relative quantity of Y4R mRNA in brainstem of refed rats in comparison to food deprived or ad lib fed rats. Consistently, plasma leptin level was elevated in refed rats in comparison to food deprived rats. Similarly, leptin-treated rats exhibited a significant increase in Y4R mRNA in brainstem as compared to saline-injected rats. Plasma leptin was significantly elevated in leptin-treated rats. These results suggest that refeeding stimulates the expression of Y4R gene in the brainstem and that leptin may be one of the peripheral factors involved in this anorectic signaling mechanism.     

Studies on a novel doughnut-shaped minitablet for intraocular drug delivery

The objective of this study was to evaluate the effect of 2 independent formulation variables on the drug release from a novel doughnut-shaped minitablet (DSMT) in order to optimize formulations for intraocular drug delivery. Formulations were based on a 3(2) full-factorial design. The 2 independent variables were the concentration of Resomer (% wt/wt) and the type of Resomer grade (RG502, RG503, and RG504), respectively. The evaluated response was the drug release rate constant computed from a referenced marketed product and in vitro drug release data obtained at pH 7.4 in simulated vitreous humor. DSMT devices were prepared containing either of 2 model drugs, ganciclovir or foscarnet, using a Manesty F3 tableting press fitted with a novel central-rod, punch, and die setup. Dissolution data revealed biphasic drug release behavior with 55% to 60% drug released over 120 days. The inherent viscosity of the various Resomer grades and the concentration were significant to achieve optimum release rate constants. Using the resultant statistical relationships with the release rate constant as a response, the optimum formulation predicted for devices formulated with foscarnet was 70% wt/wt of Resomer RG504, while 92% wt/wt of Resomer RG503 was ideal for devices formulated with ganciclovir. The results of this study revealed that the full-factorial design was a suitable tool to predict an optimized formulation for prolonged intraocular drug delivery.     

Exfoliative cytologic findings of primary pulmonary adenoid cystic carcinom: a report of 2 cases with a review of the cytologic features

BACKGROUND: Adenoid cystic carcinoma is a very rare primary pulmonary neoplasm. Cytologic findings of pulmonary washing and brushing in 2 cases of primary bronchial adenoid cystic carcinoma with special histologic features are described, with an emphasis on some points that have not been reported previously, together with the diagnostic pitfalls. CASES: Two cases of primary adenoid cystic carcinoma of the lung were diagnosed on exfoliative cytology. The patients' ages were 55 and 65 years old. Cytologic findings included large and small clusters of small cells in both 2 and 3 dimensions with occasional cystlike spaces containing mucoid material. The cells were arranged in spherical, cylindrical, basaloid and rosettelike arrangements. There were also abundant small and large mucoid globules, cylinders of homogeneous, acellular, mucous material and "cannon balls." Cytoplasmic and intranuclear round inclusions were noted in case 1. Rare findings of nuclear molding were noted. In case 2, chondromyxoid material and a bimorphic population of tumor cells caused diagnostic confusion with other salivary gland-type tumors of the lung. CONCLUSION: These cases showed characteristic cytologic findings of adenoid cystic carcinoma together with rare findings of intracellular and extracellular inclusionlike bodies, myxochondroid material, bimorphic populations and nuclear molding, which can cause diagnostic confusion with other lung tumors.     

Ultra-wide band electromagnetic radiation does not affect UV-induced recombination and mutagenesis in yeast

Cell samples of the yeast Saccharomyces cerevisiae were exposed to 100 J/m² of 254 nm ultraviolet (UV) radiation followed by a 30 min treatment with ultra-wide band (UWB) electromagnetic pulses. The UWB pulses (101–104 kV/m, 1.0 ns width, 165 ps rise time) were applied at the repetition rates of 0 Hz (sham), 16 Hz, or 600 Hz. The effect of exposures was evaluated from the colony-forming ability of the cells on complete and selective media and the number of aberrant colonies. The experiments established no effect of UWB exposure on the UV-induced reciprocal and non-reciprocal recombination, mutagenesis, or cell survival. Bioelectromagnetics 19: 128–130, 1998. © 1998 Wiley-Liss, Inc.     

Enhanced survival by vitamin A supplementation during a retrovirus infection causing murine AIDS

Infection by LP-BM5 murine leukemia virus (MuLV) produces an AIDS-like condition in mice. The viral infection suppressed the percentage of peripheral blood cells showing surface markers for macrophages, activated macrophages, T lymphocytes and activated lymphoid cells. High dietary vitamin A (retinyl palmitate) caused increased numbers of activated macrophages. It also increased the percentage of cells with markers for Ia+ cells and macrophages in the retrovirally infected mice compared to infected controls. In uninfected mice retinyl palmitate stimulated the percentage of cells with activated lymphocytes bearing IL-2R, and T cytotoxic cells. These were associated with a retarded death rate during infection with LP-BM5 murine leukemia in C57BL/6 mice. By 25 weeks of infection and 20 weeks of retinyl palmitate supplementation 71.3% survived, while 45.0% virally infected controls survived. The mice also had elevated numbers of B cells measured in the blood after 4 and 8 weeks of dietary treatment. Vitamin A stimulation may play a role in the slower death rate for retrovirally infected mice.