Isolation and pharmacological characterization of cannitoxin, a presynaptic neurotoxin from the venom of the Papuan Taipan (Oxyuranus scutellatus canni)

The Papuan taipan (Oxyuranus scutellatus canni) is widely distributed throughout much of Papua New Guinea. Although neurotoxicity is a major symptom of envenomation, no neurotoxins have been isolated from this venom. Using a series of size exclusion chromatography steps, we report the isolation of cannitoxin, a presynaptic neurotoxin (44,848 Da) that represents approximately 16% of the whole venom. The toxin displayed high phospholipase A2 (PLA2 activity (330 +/- 5 micromol/min/mg) and caused concentration-dependent (11-66 nM) inhibition of indirect (0.2 ms; 0.1 Hz; supramaximal V) twitches of the chick biventer cervicis nerve-muscle preparation without effecting nicotinic receptor agonists. Prior addition of CSL Taipan antivenom (5 U/ml) or inhibition of phospholipase A2 activity by incubation with 4-bromophenacyl bromide prevented the inhibition of twitches. Cannitoxin is composed of three different subunits, alpha, beta, and gamma, with the possibility of two beta isomers. However, only the alpha subunit displayed in vitro neurotoxic activity of its own. Thus, cannitoxin is similar in structure and pharmacology to taipoxin, which has been isolated from the closely related Australian species O. scutellatus scutellatus (coastal taipan).     

An item response theory-based pain item bank can enhance measurement precision

Cancer-related pain is often under-recognized and undertreated. This is partly due to the lack of appropriate assessments, which need to be comprehensive and precise yet easily integrated into clinics. Computerized adaptive testing (CAT) can enable precise-yet-brief assessments by only selecting the most informative items from a calibrated item bank. The purpose of this study was to create such a bank. The sample included 400 cancer patients who were asked to complete 61 pain-related items. Data were analyzed using factor analysis and the Rasch model. The final bank consisted of 43 items which satisfied the measurement requirement of factor analysis and the Rasch model, demonstrated high internal consistency and reasonable item-total correlations, and discriminated patients with differing degrees of pain. We conclude that this bank demonstrates good psychometric properties, is sensitive to pain reported by patients, and can be used as the foundation for a CAT pain-testing platform for use in clinical practice.     

Ultraviolet A (320-400 nm) modulation of ultraviolet B (290-320 nm)-induced immune suppression is mediated by carbon monoxide

Accumulating evidence suggests that suberythemogenic ultraviolet A (UVA) (320-400 nm) exposure protects against the immunosuppressive effect of ultraviolet B (290-320 nm) radiation or its epidermal photoproduct, cis-urocanic acid (cis-UCA). In skin, UVA photoimmunoprotection is mediated by the inducible antioxidant stress enzyme, heme oxygenase-1 (HO-1), which degrades heme into carbon monoxide (CO), iron, and biliverdin (reduced to bilirubin), and is important for cell survival under conditions of oxidative stress. The identity of the HO enzymatic product(s) that provide the immunoprotection is unknown. Here we examine the potential of CO to fulfill this role in hairless mouse skin, utilizing a novel CO-releasing molecule (CO-RM) to deliver CO to the skin topically. The CO-RM released CO gradually from the lotion vehicle during 3 h following its preparation, and between 50 and 500 microM, concentration-dependently protected mice against the suppression of contact hypersensitivity by either solar-simulated UV radiation (SSUVR) or cis-UCA, whereas aged CO-depleted CO-RM was inactive. Thus, the CO-RM treatment mimicked UVA-photoimmunoprotection, and identified HO-released CO as the protective mediator, providing evidence that the murine cutaneous immune system is modulated by this gaseous messenger. Preliminary evidence for involvement of guanylyl cyclase was obtained by treatment of the mouse with its specific inhibitor 1H-(1,2,4)oxadiazolo-(4,3-1)quinoxaline-1-one, which abrogated UVA photoimmunoprotection.     

Measurement of CT radiation profile width using CR imaging plates

This paper describes the procedure for using a Fuji computed radiography (CR) imaging plate (IP) for the measurement of computed tomography (CT) radiation profiles. Two sources of saturation in the data from the IP, signal and quantization, were characterized to establish appropriate exposure and processing conditions for accurate measurements. The IP generated similar profiles compared to those obtained from digitized ready-pack films, except at the profile edges, where the exposure level is low. However, when IP pixel values are converted to exposure, CR and digitized film profiles are in agreement. The full width at half maximum (FWHM) of the CT radiation profile was determined from the relationship between pixel value and exposure and compared to FWHM of the digitized optical density profile from film. To estimate the effect of scattering by the cassette material, radiation profiles were acquired from IPs enclosed in a cassette or in a paper envelope. The presence of the cassette made no difference in the value determined for FWHM. With proper exposure and processing conditions, the FWHM of 5, 10, and 15 mm collimated beams were measured using IPs to be 7.1, 11.9, and 17.0 mm and using film to be 7.2, 12.2, and 16.8 mm, respectively. Our results suggest that, under appropriate conditions, the estimation of the width of the CT radiation profile using Fuji CR is comparable to the measurement from film density described in American Association of Physicists in Medicine (AAPM) Report No. 39. Although our experiment was conducted using Fuji CR, we anticipate that CR plates from other vendors could be successfully used to measure CT beam profiles because of similar empirical relationships between pixel value and exposure.     

Ambulatory level and asymmetrical weight bearing after stroke affects bone loss in the upper and lower part of the femoral neck differently: bone adaptation after decreased mechanical loading

The aim of this 1-year prospective study of acute stroke patients was to determine the effects of walking and asymmetrical weight bearing on the loss of bone mineral in the upper and lower femoral neck. Forty patients were followed. Eight remained unable to walk, whereas 32 relearned to walk independently within 7 months (12 shortly after the stroke, 15 by 2 months, 5 by 7 months). Bone mineral density (BMD) was measured in the proximal femur within the first week after stroke and 1 year later; regional BMD changes were computed for the lower and upper femoral neck. The lower part of the femoral neck is mainly influenced by compressive stresses of the hip, the upper part by tensile stresses during walking. When comparing mean BMD loss in groups of patients according to when they relearned to walk, a statistically significant trend in BMD loss was found in the lower femoral neck on both the paretic and nonparetic sides (p < 0.01 and p = 0.01, respectively), whereas, for the upper femoral neck, no significant trend was seen (p >/= 0.1). In addition, the body weight distribution during standing was assessed by use of a force-plate in 38 patients who could stand independently at the 7 month evaluation. The only significant correlation between changes in BMD and asymmetrical weight bearing was found in the lower femoral neck on the paretic side (r = 0.6, p < 0.001). In conclusion, this study shows that the reduction in BMD in the femoral neck occurs mainly in the lower part of the neck and on the paretic side. The BMD loss depended on when or if the patients relearned to walk, but also on the amount of body weight born on the paretic leg. Thus, measuring the lower part of the femoral neck gives a better estimate of the impact of gait and weight bearing than measuring the total femoral neck.