Simultaneous determination of azathioprine and 6-mercaptopurine by high-performance liquid chromatography

A specific, sensitive, single-step solid-phase extraction and reversed-phase high-performance liquid chromatographic method for the simultaneous determination of plasma 6-mercaptopurine and azathioprine concentrations is reported. Following solid-phase extraction, analytes are separated on a C₁₈ column with mobile phase consisting of 0.8% acetonitrile in 1 mM triethylamine, pH 3.2, run on a gradient system. Quantitation limits were 5 ng/ml and 2 ng/ml for azathioprine and 6-mercaptopurine, respectively. Peak heights correlated linearly to known extracted standards for 6-mercaptopurine and azathioprine (r = 0.999) over a range of 2–200 ng/ml. No chromatographic interferences were detected.     

Knowledge,Attitudes, and Acceptability of Pre-Exposure Prophylaxis among Individuals Living with HIV in an Urban HIV Clinic

Introduction

Pre-exposure prophylaxis (PrEP) is an effective tool to reduce HIV transmission. The primary objective of this study was to assess awareness of PrEP by individuals living with HIV (HIV+) and acceptance of its use for their HIV negative (HIV-) partners.

Methods

A cross sectional survey was conducted among individuals living with HIV who received care at an urban HIV clinic between January 2013 and June 2013. The survey examined knowledge, attitudes, and acceptability of PrEP, and perception of transmission risk of HIV. Chi-Square test and Fisher''s Exact test were used to compare proportions.

Results

Among 206 subjects living with HIV, 15.3% (32) had heard of PrEP. Men who have sex with men (MSM) were more likely to be aware of PrEP than all others (p = 0.003). Once educated about PrEP those who believed PrEP would reduce their partner’s risk for HIV were more likely to recommend PrEP to their partner (p<0.001). 92% of all respondents said they would be “extremely likely/likely” to discuss PrEP use with their provider. Of 159 subjects whose main partner was HIV-, MSM (p = 0.007), male participants (p = 0.044), and those who were consistently taking meds (p = 0.049) were more likely to be aware of PrEP. Those who perceived they were at risk of transmitting HIV (p<0.001) and those who were consistently taking meds (0.049) were more likely to agree that PrEP could reduce the risk of HIV to their partners.

Conclusion

This study illustrates a low awareness of PrEP but once educated the willingness of a cohort of individuals living with HIV to recommend PrEP to their partners. Our findings demonstrate the importance of providers informing their patients living with HIV about PrEP, as these persons are an underutilized link to support the uptake of PrEP by their HIV- partners.     

Inhibition of fructose bisphosphatase and stimulation of phosphofructokinase by a stable isosteric phosphonate analog of fructose 2,6-bisphosphate

We describe the synthesis of a mixture of D-manno- and D-gluco-2,5-anhydro-1-deoxy-1-phosphonohexitol 6-phosphate via a Horner-Emmons reaction of 2,3,5-tri-O-benzyl-beta-D-arabinofuranose followed by phosphorylation of the equivalent 6-position and subsequent deprotection. This mixture inhibits fructose-1,6-bisphosphatase; the concentration required for half-maximal effect in the presence of 25 microM AMP is approximately 6 microM. The mixture of analogs also stimulates 6-phosphofructo-1-kinase from rabbit liver; the concentration required to reach one-half Vmax was found to be ca. 25 microM at 0.25 mM fructose 6-phosphate and 50 microM AMP. These analogs have replaced the labile anomeric phosphate of fructose 2,6-bisphosphate with a stable methylenephosphonate, and could be of great interest due to their appropriate physiological effects and their chemical stability.