No abstract

The combination of anticancer drugs in nanoparticles has great potential as a promising strategy to maximize efficacies by eradicating resistant, reduce the dosage of the drug and minimize toxicities on the normal cells. Gemcitabine (GEM), a nucleoside analogue, and atorvastatin (ATV), a cholesterol lowering agent, have shown anticancer effect with some limitations. The objective of this in vitro study was to evaluate the antitumor activity of the combination therapy of GEM and ATVencapsulated in a microemulsion (ME) formulation in the HCT116 colon cancer cells. The cytotoxicity and efficacy of the formulation were assessed by the 3- (4,5dimethylthiazole-2-yl)-2,5-diphyneltetrazolium bromide (MTT) assay. The mechanism of cell death was examined by observing the morphological changes of treated cells under light microscope, identifying apoptosis by using the ApopNexin apoptosis detection kit, and viewing the morphological changes in the chromatin structure stained with 4′,6-diamidino-2-phenylindole (DAPI) under the inverted fluorescence microscope. It has been found that reducing the concentration of GEM loaded on ME (GEM-ME) from 5μM to 1.67μM by combining it with 3.33μM of ATV in a ME formulation (GEM/2ATV-ME) has preserved the strong cytotoxicity of GEM-ME against HCT116 cells. The current study proved that formulating GEM with ATV in ME has improved the therapeutic potential of GEM and ATV as anticancer drugs.

The specific activities of adenylyl and guanylyl cyclases, the cAMP and cGMP phosphodiesterase of rat kidney, liver, heart and brain were examined. Of all tissues, kidney has the highest adenylyl cyclase specific activities by mean (± SD) of (145 ± 14 pmol/min/mg protein) followed by that of heart (113 ± 21 pmol/min/mg protein), brain (101 ± 8 pmol/min/mg protein) and liver (92 ± 9 pmol/min/mg protein). The specific activity of particulate guanylyl cyclase was the highest in liver (26 ± 1 nmol/min/mg protein), but the soluble form predominated in kidney (40 ± 2 nmol/min/mg protein). In contrast to the other tissues examined, brain showed relatively high cAMP and cGMP phosphodiesterase activities. The kinetic properties of the adenylyl cyclases and cAMP phosphodiesterases were also investigated. The optimum pH for both types of activity was found to be at 7.4. Subcellular fractionation of the kidney to locate adenylyl cyclase activity revealed that both the mitochondrial and the microsomal fractions had higher specific activities than that of the nuclear fraction. Studies on the tissue distribution of cyclic nucleotide PDE activity as well as adenylyl and guanylyl cyclase showed that it is widely distributed in intra and extracellular and they have an important role in signal and nucleotide transdaction.

No abstract

This study conducted a clinical trial to evaluate the relieving effects of Saussurea lappa on migraine patients. The results showed that calcium and magnesium concentrations decreased significantly in patients while serotonin increased after two weeks of treatment with Saussurea lappa. The drug (Amitriptyline 20mg/day and Ibuprofen 400mg/day) decreased alkaline phosphatase level significantly, while Saussurea lappa had no effect on its level. This study found Saussurea lappa a safe and effective alternative therapeutic agent which indicated that this root could have an effect in relieving headaches (migraine).