Inhibition by oral N-acetylcysteine of cigarette smoke-induced "bronchitis" in the rat

Specific pathogen-free rats were exposed to the cigarette smoke (CS) of 25 cigarettes daily for 14 days and concurrently given N-acetylcysteine (Nac) as 1% of their drinking water (average daily dose 973 mg/kg). The thickness of the epithelium was measured at four airway levels and the numbers of mucus-containing secretory cells, stained for neutral or acidic glycoprotein (NGP or AGP respectively), were counted in surface epithelium at eight airway levels. Cigarette smoke increased the thickness of the epithelium at three of the airway levels studied by between 37 and 72%. The number of secretory cells was increased at all airway levels distal to the upper trachea by between 102 and 421%. Secretory cells containing NGP were reduced in number but this was more than offset by a large increase in the number of secretory cells containing AGP at all airway levels. N-acetylcysteine inhibited CS-induced epithelial thickening. Nac also inhibited the CS-induced increase in the number of secretory cells with AGP, but had little effect on the CS-induced reduction in the number of cells with NGP. Thus, prophylactic oral N-acetylcysteine led to an overall inhibition of CS-induced mucous cell hyperplasia and epithelial hypertrophy. The results suggest a novel anti-inflammatory action for a drug with known mucolytic effects.     

West Nile virus preferentially transports along motor neuron axons after sciatic nerve injection of hamsters

Prior findings led us to hypothesize that West Nile virus (WNV) preferentially transports along motor axons instead of sensory axons. WNV is known to undergo axonal transport in cell culture and in infected hamsters to infect motor neurons in the spinal cord. To investigate this hypothesis, WNV was injected directly into the left sciatic nerve of hamsters. WNV envelope-staining in these hamsters was only observed in motor neurons of the ipsilateral ventral horn of the spinal cord, but not in the dorsal root ganglion (DRG). To evaluate the consequence of motor neuron infection by WNV, the authors inoculated wheat germ agglutinin—horseradish peroxidase (WGA-HRP) 9 days after WNV sciatic nerve injection, and stained the spinal cord and the DRG for HRP activity 3 days later. The degree of HRP-staining in DRG was the same in WNV- and sham-infected animals, but the HRP-staining in the motor neuron in the ventral horn was considerably less for WNV-infected hamsters. To investigate the mechanism of WNV transport, hamsters were treated with colchicine, an inhibitor of membranous microtubule-mediated transport. The intensity of the WNV-stained area in the spinal cord of colchicine-treated hamsters at 6 days after WNV infection were significantly reduced (P≤.05) compared to the placebo-treated hamsters. These data suggest that WNV is preferentially transported through the motor axons, but not the sensory axons, to subsequently infect motor neurons and cause motor weakness and paralysis.     

Prostate thermal therapy with high intensity transurethral ultrasound: the impact of pelvic bone heating on treatment delivery.

PURPOSE: This study was designed to assess pelvic bone temperature during typical treatment regimens of transurethral ultrasound thermal ablation of the prostate to establish guidelines for limiting bone heating. METHODS: Treatment with transurethral planar, curvilinear, and sectored tubular applicators was simulated using an acoustic and biothermal pelvic model that accommodates applicator sweeping, boundary temperature control, and changes in perfusion and attenuation with thermal dose to more accurately model ultrasound energy penetration. The effects of various parameters including power and frequency (5-10 MHz) on bone heating were assessed for a range of prostate cross-sections (3-5 cm) and bone distances (1-3 cm). RESULTS: All devices can produce significant bone heating (temperatures >50 degrees C, thermal dose >240 EM(43 degrees C)) without optimization of applied frequency or power for bone <3 cm from the prostate boundary. In small glands ( approximately 3 cm) increasing operating frequency of curvilinear and planar devices can increase bone temperatures, whereas the tubular applicator can be used at 10 MHz to avoid likely bone damage. In larger prostates (4-5 cm wide) increasing frequency reduces bone heating but can substantially increase treatment time. Lowering power can reduce bone temperature but may increase thermal dose by increasing treatment duration. All applicators can be used to treat glands 4-5 cm with limited bone heating by selecting appropriate power and frequency. CONCLUSIONS: Pubic bone heating during ultrasound thermal therapy of the prostate can be substantial in certain situations. Successful realization of this therapy will require patient-specific treatment planning to optimally determine power and frequency in order to minimize bone heating.     

Brain tissue reaction following intracerebral injection of free or liposomally encapsulated BSH

Boron neutron capture therapy (BNCT) is a potentially valuable treatment of malignant brain gliomas. A primary requirement for successful BNCT is achieving high local concentration of boron drugs in tumors. Intratumoral injection of liposomes containing boron drug has potential to meet this requirement and could prove to be of significance for BNCT. The brain tissue reaction following the intracerebral injection of a boron drug, BSH, either in solution form or in liposomally encapsulated form, was studied in rats. On histological examination, no evidence of tissue reaction was found after injecting BSH solution, suggesting that high local concentration of BSH was well tolerated. Injection of liposomal BSH was characterized by phagocytic activity at the site of injection, which was regressing by 24 h. Neither group of animals exhibited any signs of abnormal behavior or neurologic deficit. Direct intracerebral injection of BSH liposomes as per-formed in this report could be regarded as tolerable.