Swellable elementary osmotic pump (SEOP): an effective device for delivery of poorly water-soluble drugs.

A new type of elementary osmotic pump (EOP) tablet for efficient delivery of poorly water-soluble/practically insoluble drugs has been designed. Drug release from the system, called swellable elementary osmotic pump (SEOP), is through a delivery orifice in the form of a very fine dispersion ready for dissolution and absorption. SEOP tablets were prepared by compressing the mixture of micronized drug and excipients into convex tablets. Factors affecting the release of drug from the SEOP tablets containing a poorly water-soluble drug, indomethacin, have been explored. The release behaviour of indomethacin from different formulations of this dosage form was studied at pH 6.8 for a period of 24h. The formulations were compared based on four comparative parameters, namely, D(24h) (total release after 24h), t(L) (lag time), RSQ(zero) (R square of zero order equation) and D%(zero) (percentage deviation from zero order kinetics). The drug release profile from osmotic devices showed that the type of polymer in the core formulation can markedly affect the drug release. The results showed that concentration of wetting agent in the core formulation was a very important parameter in D(24h) and release pattern of indomethacin from SEOP system. Increasing the amount of wetting agent to an optimum level (60mg) significantly increased D(24h) and improved zero order release pattern of indomethacin. Increasing concentration of caster oil (hydrophobic) in the semipermeable membrane of the device or hydrophilic plasticizer (glycerin) in coating formulation markedly increased t(L) and decreased D(24h). The results also demonstrated that aperture size is a critical parameter and should be optimized for each SEOP system. Optimum aperture diameter for the formulations studied here was determined to be 650microm for zero order release pattern. t(L) and D%(zero) were dramatically decreased whereas D(24h) and RSQ(zero) increased with increasing the aperture size to optimum level. This study also revealed that optimization of semipermeable membrane thickness is very important for approaching zero order kinetics.     

Synthesis,docking and acetylcholinesterase inhibitory assessment of 2-(2-(4-Benzylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives with potential anti-Alzheimer effects

Background

Alzheimer’s disease (AD) as neurodegenerative disorder, is the most common form of dementia accounting for about 50-60% of the overall cases of dementia among persons over 65 years of age. Low acetylcholine (ACh) concentration in hippocampus and cortex areas of the brain is one of the main reasons for this disease. In recent years, acetylcholinesterase (AChE) inhibitors like donepezil with prevention of acetylcholine hydrolysis can enhance the duration of action of acetylcholine in synaptic cleft and improve the dementia associated with Alzheimer’s disease.

Results

Design, synthesis and assessment of anticholinesterase activity of 2-(2-(4-Benzylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives showed prepared compounds can function as potential acetylcholinesterase inhibitor. Among 12 synthesized derivatives, compound 4a with ortho chlorine moiety as electron withdrawing group exhibited the highest potency in these series (IC₅₀ = 0.91 ± 0.045 μM) compared to donepezil (IC₅₀ = 0.14 ± 0.03 μM). The results of the enzyme inhibition test (Ellman test) showed that electron withdrawing groups like Cl, F and NO₂ can render the best effect at position ortho and para of the phenyl ring. But compound 4g with methoxy group at position 3(meta) afforded a favorable potency (IC₅₀ = 5.5 ± 0.7 μM). Furthermore, docking study confirmed a same binding mode like donepezil for compound 4a.

Conclusions

Synthesized compounds 4a-4l could be proposed as potential anticholinesterase agents.     

Effects of a kappa-receptor agonist U-50488 on bulbar respiratory neurons and its antagonistic action against the mu receptor-induced respiratory depression in decerebrate cats

The function of kappa receptor-mechanisms in bulbar respiratory network was investigated in decerebrate cats. Intravenous injection of U-50488 (0.3-3.0 mg/kg) dose-dependently decreased the phrenic nerve discharge and shortened inspiration and expiration. U-50488 caused hyperpolarization, and decreased input resistance and the action potential discharge in respiratory neurons. The effects of U-50488 were antagonized by nor-binaltorphimine. DAMGO (0.3 mg/kg, i.v.) decreased the phrenic discharge and prolonged inspiration and expiration. U-50488 partially reversed the respiratory depression induced by DAMGO. These results suggest that the activation of K receptors by itself depresses the central respiratory activity, while it opposes the mu receptor-mediated respiratory depression.     

Three new lignans from the seeds of Saussurea involucrata

Three new lignans, arctigenin-4-O-(6'-O-acetyl-β-d-glucoside) (1), arctigenin-4-O-(2'-O-acetyl-β-d-glucoside) (2), and arctigenin-4-O-(3'-O-acetyl-β-d-glucoside) (3), together with two known lignans, were isolated from the seeds of Saussurea involucrata. Their structures were established by spectroscopic methods, mainly 1D and 2D NMR, and mass spectral analysis.     

Inadvertent rubella vaccination of pregnant women: evaluation of possible transplacental infection with rubella vaccine

During mass campaign for measles/rubella vaccination on December 2003 in Iran, many pregnant women have vaccinated mistakenly. These women were grouped to susceptible and immune against rubella before vaccination by the status of IgG avidity response to rubella vaccine, then susceptible women were followed up to delivery time and their neonates were followed up to one year. In five neonates that were born from susceptible women, rubella-specific IgM has detected in cord blood sera, but they have not shown signs compatible to congenital rubella syndrome.     

Characterization of Echinococcus granulosus isolates from human, sheep and camel in Iran.

In the present study, Echinoccocus granulosus isolates collected from human, sheep and camel samples in Iran were characterized based on rostellar hook morphology of protoscoleces as well as PCR-RFLP. Morphological study on human and animal isolates showed the presence of two distinct strains of the parasite, one in sheep and the other one in camels. In this regard, rostellar hook of sheep isolates were significantly different from those of camel origin, meanwhile human isolates were found to be similar to those isolated from sheep. Molecular analysis of the ITS1 region of rDNA derived from human, sheep and camel isolates were in agreement with the morphological findings. Based on the PCR-RFLP method, the sheep and human isolates appeared to pertain to the same genotype and the camel isolates were appeared to pertain to a different genotype.     

Imiquimod for the treatment of Bowen's disease and invasive squamous cell carcinoma

Topical imiquimod is an immune response modifier FDA approved for the treatment of anogenital warts. Recent studies have reported its effectiveness in the treatment of some types of basal cell carcinomas. There have also been some case reports and case series reporting success treating of squamous cell carcinoma in situ with imiquimod. We report two patients with squamous cell carcinoma in situ and one with invasive squamous cell carcinoma treated with 5% imiquimod cream. Lesions were located on shin, posterior shoulder, and nasal tip. 5% imiquimod cream was applied at night for six weeks. Side effects included erythema and crusting in one patient. Biopsies taken four weeks after treatment revealed no residual squamous cell carcinoma in situ or squamous cell carcinoma. Topical 5% imiquimod cream is becoming established as a promising treatment for squamous cell carcinoma in situ. It also seems to be an alternative treatment for some cases of squamous cell carcinoma.