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We have developed large-scale efficient procedures for the conversion of commercially available [(13) C]- or [(2) H3 ,(13) C]methanol and (13) CO2 or (13) C-labeled bromoacetic acid to 2-(phenylthio)[1,2-(13) C2 ]-, [1-(13) C]-, and [2-(13) C]acetic acid. The resulting derivatives are versatile, chemically stable, and nonvolatile two-carbon labeling precursors. We have used the (13) C-isotopomers of 2-(phenylthio)acetic acid in the synthesis of (13) C-labeled acrylic acid, methacrylic acid, and trans-crotonic acid., (Copyright © 2013 John Wiley & Sons, Ltd.)

Objective: To determine the gene expression profile of pelvic ganglia neurones after bilateral cavernosal nerve resection (BCNR) and subsequent treatment with sildenafil in relation to neurotrophic-related pathways., Materials and Methods: Fisher rats aged 5 months were subjected to BCNR or sham operation and treated with or without sildenafil (20 mg/kg body-weight in drinking water) for 7 days. Total RNA isolated from pelvic ganglia was subjected to reverse transcription and then to quantitative reverse transcriptase-polymerase chain reaction (PCR) with the RAT-neurotrophic array. Results were corroborated by real-time PCR and western blotting. Another set of animals were injected with a fluorescent tracer at the base of the penis, 7 days before BCNR or sham operation, and were sacrificed 7 days after surgery. Sections of pelvic ganglia were used for immunohistochemistry with antibodies against neurturin, neuronal nitric oxide synthase, tyrosine hydroxylase and glial cell line-derived neurotrophic factor receptor α2., Results: A down-regulation of the expression of neuronal nitric oxide synthase accompanied by changes in the level of cholinergic neurotrophic factors, such as neurturin and its receptor glial cell line-derived neurotrophic factor receptor α2, artemin, neurotrophin-4 and cilliary neurotrophic factor, was observed 7 days after BCNR in pelvic ganglia neurones. Treatment with sildenafil, starting immediately after surgery, reversed all these changes at a level similar to that in sham-operated animals., Conclusions: Sildenafil treatment promotes changes in the neurotrophic phenotype, leading to a regenerative state of pelvic ganglia neurones. The present study provides a justification for the use of phosphodiesterase 5 inhibitors as a neuroprotective agent after BCNR., (© 2012 BJU International.)

Sulfur mustard agent (HD) (2,2'-dichloroethyl sulfide), a Schedule I compound on the Chemical Weapons Convention Schedule of Chemicals, remains a public health concern because it is simple to synthesize and it is in the chemical weapon stockpiles of several countries. A sensitive, rapid, accurate, and precise method was developed to quantitate trace levels of 1,1'-sulfonylbis [2-(methylthio) ethane] (SBMTE) in human urine as a means of assessing exposure to HD. The method used immobilized liquid-liquid extraction with diatomaceous earth, followed by the analysis of the urine extract using isotope-dilution gas chromatography-tandem mass spectrometry. Relative standard deviations were less than 8.6% at 1 ng/mL and 3.6% at 20 ng/mL. The limit of detection for SBMTE was 0.038 ng/mL in 0.5 mL of urine.

Sulfur mustard (HD), or bis(2-chloroethyl)sulfide, has several urinary metabolites that can be measured to assess human exposure. These metabolites include the simple hydrolysis product thiodiglycol (TDG) and its oxidative analogue, TDG-sulfoxide, as well as metabolites of the glutathione/b-lyase pathway 1,1'-sulfonylbis[2-(methyl-sulfinyl)ethane] (SBMSE) and 1-methyl-sulfinyl-2-[(methylthio)ethyl-sulfonyl]ethane (MSMTESE). Current methods focus on either the TDG or the b-lyase metabolites. We have developed a single method that measures products of both metabolic branches, with the reduced compound of SBMSE and MSMTESE, 1,1'-sulfonylbis [2(methylthio)ethane] (SBMTE), as the definitive analyte and TDG as a confirmation analyte. Sample preparation included b-glucuronidase hydrolysis for TDG-glucuronide conjugates, titanium trichloride reduction of sulfoxides to SBMTE and TDG, solid-phase extraction, and a chemical derivatization. We analyzed samples using gas chromatography-tandem mass spectrometry with quantitation using isotope-dilution calibration. The method limits of detection for TDG and SBMTE were 0.5 ng/mL and 0.25 ng/mL, respectively, with relative standard deviations of less than 10%. Urine samples from individuals with no known exposure to mustard agent HD had measurable concentrations of TDG, but no SBMTE was detected. The geometric mean concentration of TDG was 3.43 ng/mL, with concentrations ranging from < 0.5 ng/mL to 20 ng/mL.