The purpose of this work was to develop a topical formulation of imiquimod, a novel immune response modifier, to induce local cytokine production for the treatment of external genital and perianal warts. A pH-solubility profile and titration data were used to calculate a pKa of 7.3, indicative of a weak base. Solubility experiments were conducted to identify a solvent that dissolves imiquimod to achieve a 5% formulation concentration. Studies to select surfactants, preservatives, and viscosity-enhancing excipients to formulate an oil-in-water cream indicated that fatty acids were the preferred solvent for topical imiquimod formulations, and isostearic acid (ISA) was selected. A relationship existed between the fatty acid composition of four commercially available ISA sources and the solubility of imiquimod. A combination of polysorbate 60, sorbitan monostearate, and xanthan gum was used to produce a physically stable cream. The preservative system included parabens and benzyl alcohol to meet the USP criteria for preservative activity. An in vitro method was developed to demonstrate that imiquimod was released from the formulation. Topical application of the formulation induced local cytokine activity in mice.
Cardiovascular disease (CVD) is often referred to several different diseases and disorders of the heart and blood vessels that constitute cardiovascular or heart disease. CVD is one of the leading causes of death worldwide. Atherosclerosis is the most common pathological process leading to CVD, a disease of medium to large arteries that majorly causes heart attacks and strokes. The pathogenesis of atherosclerosis lesion is a very complex process that is associated with thickening of the intima layer, weakening of underlying intima. Many components of the vascular, metabolic, and immune systems are involved in this process. These lesions have been presented even in teenagers and young adults and although not clinically significant at this stage, these lesions possess the potential to develop into clinically relevant lesions later on in over decades of life. This article will give an overview relationship between atherosclerosis and cardiovascular disease.
Breast cancer is one of the most leading causes of death in females all over the world. Although, the incidence rate of breast cancer is low, the death proportion is relatively high. For breast cancer patients, the recurrence ratio is rare, yet it still happens. The highest risk of recurrence usually happens at the early time of treatment, and its severeness depends on the diagnosed stage and the size of the tumor. However, the recurrence prognostic of breast cancer still limited due to the poor prediction strength of input data. Therefore, in this study we used four independent data sets (n = 793) with the same chipsets (HG-U133A) of breast cancer patients to investigate a 67 gene signature used in further building the prognostic model for breast cancer patients. Our results finally confirmed that a 67 gene set was significantly associated with the recurrence (RFS) (p = 1.66e−17), and overall survival (OS) (p = 9.27e−06). Besides, the gene signature also correlated with survival outcomes, such as RFS (p = 0.00167), and distant metastasis-free survival (DMFS) (p < 0.001). Remarkably, our classification analysis results reveal that the breast cancer patients who were categorized into the low-risk group tend to have significantly associated with the longer recurrence time in both training and validation data sets. In conclusion, the 67 gene signature should be considered as potential candidates to be used in building up models or integrated into the current treatment regime for breast cancer.
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