A nanoparticle‐coupled T2 peptide induces immune tolerance and ameliorates chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in mice model

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease of unclear etiology. Precise treatment of CP/CPPS is not available due to lack of specific cause; however, autoimmunity is the most valid theory. We develop a new treatment strategy that involves synthesis and coupling of biodegradable nanoparticles to antigenic T2 peptide to induce immune tolerance in CP/CPPS mice models. A total of 50 male C57BL/6 mice were randomized into five groups, that is, naïve, Model, PLGA‐PEMA, PLGA‐PEMA‐OVA_323‐339, and PLGA‐PEMA‐T2 group. All groups except naïve were injected subcutaneously on day 0 with 0.2 mL of T2 peptide with CFA to generate valid CP/CPPS models. After successful induction of CP/CPPS, Model group, PLGA‐PEMA, PLGA‐PEMA‐OVA, and PLGA‐PEMA‐T2 groups were treated with 0.15 mL of normal saline, 0.2 mg of PLGA‐PEMA and PLG‐PEMA‐T2 and 0.3 mg PLGA‐PEMA‐OVA nanoparticles, respectively, on day 28. Hematoxylin and eosin staining, and ELISA were used to evaluate the variation in CP/CPPS manifestations and seral level of IL‐10 in each group. Pain threshold and voiding behavior were also recorded for every group. Mice treated with PLGA‐PEMA‐T2 exhibited enhanced pain threshold, reduced urine frequency, and prostate pathology. Furthermore, serum level of inflammatory mediators (TNF‐α and CRP) were reduced and anti‐inflammatory IL‐10 was enhanced in PLGA‐PEMA‐T2 group as compared to other groups. Our results demonstrate that PLGA‐PEMA‐T2 nanoparticle ameliorates disease manifestations in CP/CPPS mice models and upregulates IL‐10 which is essential for tolerance induction. This strategy highlights the new therapeutic approach utilizing biodegradable nanoparticles for the treatment of CP/CPPS.     

Molecular recognition of sugars by lanthanide (III) complexes of a conjugate of N,N‐bis[2‐[bis[2‐(1, 1‐dimethylethoxy)‐2‐oxoethyl]amino]ethyl]glycine and phenylboronic acid

A novel conjugate of phenylboronic acid and an Ln(DTPA) derivative, in which the central acetate pendant arm was replaced by the methylamide of L ‐lysine, was synthesized and characterized. The results of a fit of variable ¹⁷O NMR data and a ¹H NMRD profile show that the water residence lifetime of the Gd(III) complex (150 ns) is shorter than that of the parent compound Gd(DTPA)^2? (303 ns). Furthermore, the data suggest that several water molecules in the second coordination sphere of Gd(III) contribute to the relaxivity of the conjugate. The Ln(III) complexes of this conjugate are highly suitable for molecular recognition of sugars. The interaction with various sugars was investigated by ¹¹B NMR spectroscopy. Thanks to the thiourea function that links the phenylboronic acid targeting vector with the DTPA derivative, the interactions are stronger than that of phenylboronic acid itself. In particular, the interaction with N‐propylfructosamine, a model for the glucose residue in glycated human serum albumin (HSA), is very strong. Unfortunately, the complex also shows a rather strong interaction with hexose‐free HSA (K_A = 705 ± 300). Copyright © 2007 John Wiley & Sons, Ltd.     

Regional V˙A/Q˙ ratios in man using 133Xe and single photon emission computed tomography (SPECT) corrected for attenuation

We describe a technique to obtain non-invasively regional pulmonary ventilation–perfusion ratios (V˙_A/Q˙) using single photon emission computed tomography (SPECT) and continuous infusion of ¹³³Xe. Single photon transmission tomography was used for attenuation correction, for delineation of the lungs and for V˙_A/Q˙ calculations. Data are presented for six normal subjects and compared to those for two patients with moderate chronic obstructive pulmonary disease (COPD). The mean V˙_A/Q˙ for the whole lung of the normal subjects ranged from 0·49 to 0·65, group mean 0·56 ± 0·07 (1 SD), and there was no significant difference between the right and left lung. The consistently too low V˙_A/Q˙ values are related to the inability to measure regional blood volume and the low resolution of the scintillation camera, giving an under-estimation of tracer input. For the normal subjects, the dispersion of V˙_A/Q˙, as defined by the standard deviation of the individual distribution functions, ranged from 0·12 to 0·19. One of the patients was characterized by a low mean V˙_A/Q˙ of 0·35, and the other patient had a wide dispersion (SD) of V˙_A/Q˙ of 0·37. In the normal subjects, a consistent V˙_A/Q˙ gradient was found only in the ventrodorsal direction. ¹³³Xe and SPECT can be used to obtain meaningful biological information regarding ventilation/perfusion relationships of potential clinical value.