Addiction, cognitive decline and therapy: seeking ways to escape a vicious cycle.

Any type of behavioral change is an effortful process. Thus, the process of behavioral therapy, where clients seek to change maladaptive behavioral patterns, requires high-level cognitive engagement. It is unfortunate, then, that cognitive impairment is a feature of substance use disorders (SUDs), and especially because the domains that tend to be impaired are the very ones involved in the process of therapeutic behavioral change. In this review, we compare the cognitive profile that is frequently observed with chronic SUD with the skills that are required to initiate and sustain behavioral change during rehabilitation. Furthermore, we look to new therapeutic developments that seek to improve cognitive function. We propose that the use of these cognitive enhancing agents as adjuncts to behavioral therapy should help to overcome some of the cognitive barriers imposed by the disorder itself, and hence reduce the chance of relapse.

The effects of anterior load carriage on lower limb gait parameters during obstacle clearance.

The purpose of this study was to assess the effect of anterior load carriage on obstacle-crossing behaviour, with a focus on lower limb gait parameters. Nine male participants (age 23+/-1.8 years, height 176+/-5.0cm) volunteered. Participants either walked without a load (No Load), or carried a load (2KG (empty box), 5KG, 10KG), and stepped over a 20cm obstacle. Vision of the obstacle was obscured 1.0m to 1.3m prior to the obstacle. Significant correlations were found between trail limb toe distance and lead limb toe clearance, in the 2KG, 5KG, and 10KG conditions. Toe clearance increased with load (No Load, 147.3+/-13.9mm; 2KG, 162.5+/-15.6mm; 5KG, 167.6+/-17.6mm; 10KG, 173.9+/-17.5mm; p<0.0001). Trail limb toe distance, trail limb toe distance variability, lead heel distance variability, and lead limb toe clearance variability were greater in the 2KG, 5KG, and 10KG conditions, compared with the No Load condition. Participants adopted a conservative gait pattern during obstacle crossing when carrying a load, evidenced by increasing toe clearance, which may have been influenced by availability of visual information regarding obstacle position. In contrast with previous literature, increased lead limb toe clearance may have been associated with absence of relative surface height difference pre- and post-obstacle crossing.

D-Aspartate oxidase and D-amino acid oxidase are localised in the peroxisomes of terrestrial gastropods.

D-Aspartate oxidase and D-amino acid oxidase were found in high activity in the tissues of representative species of terrestrial gastropods. Analytical subcellular fractionation demonstrated that both of these oxidases co-localised with the peroxisome markers, acyl-CoA oxidase and catalase, in the digestive gland homogenate. Electron microscopy of peak peroxisome fractions showed particles of uniform size with generally well preserved variably electron-dense matrices bounded by an apparently single limiting membrane. Many of the particles exhibited a core region of enhanced electron density. Catalase cytochemistry of peak fractions confirmed the peroxisome identity of the organelles. Peroxisome-enriched subcellular fractions were used to investigate the properties of gastropod D-aspartate oxidase and D-amino acid oxidase activities. The substrate and inhibitor specificities of the two activities demonstrated that two distinct enzymes were present analogous to, but not identical to, the equivalent mammalian peroxisomal enzymes.

Atmospheric mercury speciation: laboratory and field evaluation of a mist chamber method for measuring reactive gaseous mercury.

Knowledge of atmospheric mercury speciation is critical to modeling its fate. Thus there is a crucial need for reliable methods to measure the fraction of gaseous atmospheric Hg which is in the oxidized Hg(II) form (termed reactive gaseous mercury, RGM). We have developed a novel method for measurement of RGM using a refluxing mist chamber, and we recently reported the results of sampling campaigns for RGM in Tennessee and Indiana. In general, measured RGM levels were about 3% of total gaseous mercury (TGM), and our results support prevailing hypotheses about the nature and behavior of RGM in ambient air. Because its use for RGM is growing, we now report in more detail the development and testing of the mist chamber method. Several styles of mist chambers have been investigated. The most versatile design employs a single nebulizer nozzle and can operate at flows of 15-20 L/min. The water-soluble Hg is collected in ca. 20 mL of absorbing solution, which is then analyzed for Hg(II) by SnCl2 reduction and CVAFS. One-hour samples (ca. 1 m3 of air) generally contain 50-200 pg of RGM. The method detection limit for 1-h samples is approximately 6-10 pg/m3. Thus short sample times can reveal temporal variations in RGM that would not otherwise be observable. The efficiency of collecting RGM in mist chambers is highly dependent on Cl- concentration in the absorbing solution, in keeping with equilibrium calculations. Artifact formation of Hg(II) by oxidation of Hg0 under ozone ambient conditions appears to be sufficiently slow so as to be negligible for the short (ca. 1 h) runs that are typically employed. We observed no significant error from cosampled particles or aerosols in rural nonimpacted air samples. We have developed a simple approach to analyzing mist chamber samples in the field using an automated Hg sampler.

Zonal rotor purification and characterization of "mannosomes": a tubular membrane system in gastropod mollusc digestive gland.

Mannitol oxidase (manox) is an H2O2-generating oxidase apparently unique to molluscs and especially abundant in alimentary tissues. In the digestive gland it is localized to an organelle ("mannosome") that forms an unusual tubular membrane system. We have developed a novel centrifugation procedure for >100-fold purification of these membranes in 20% yield from approximately 30 g of digestive gland of the slug Arion ater. Mannosomes from several other gastropod species are also substantially purified by the procedure. Four successive density gradient separations are employed which minimize structural damage by exploiting near isosmotic conditions early on and by completely avoiding traumatic pelleting and resuspension. Plasma membrane contamination is reduced by digitonin-induced density perturbation. The purified preparation is characterized by a predominant 68-kDa integral membrane protein and retains the in situ appearance of hexagonally arranged tubules with an enveloping outer membrane.

A two-year dietary carcinogenicity study of the antiestrogen toremifene in Sprague-Dawley rats.

The carcinogenic potential of the nonsteroidal triphenylethylene antiestrogen toremifene (Fareston) was evaluated in a standard 104-week rat dietary carcinogenicity study. The doses were 0, 0.12, 1.2, 5.0 and 12 mg/kg/day and the number of animals 50/sex/dose group. The body weight gain and food consumption were monitored once weekly (study weeks 1-16) or once every four weeks thereafter (study weeks 17-104). Blood samples were taken at weeks 34, 52 and 104 and the plasma concentrations of toremifene, as well as the two main metabolites (deaminohydroxy)toremifene and N-demethyltoremifene, were measured. All doses of toremifene reduced food intake and body weight gain. Toremifene caused a significant reduction in mortality, which was mainly due to reduced incidences of pituitary tumors. This was evident in all dose groups. Drug-related decrease of mammary tumors in females (at all doses) and testicular tumors in male rats (doses > or = 1.2 mg/kg/day) were also evident. The incidence of the preneoplastic foci of basophilic hepatocytes were significantly decreased in treated female groups. Toremifene induced no preneoplastic or neoplastic lesions. Based on histopathology, no obvious toxicity could be observed. Drug-related changes were observed in the genital organs, thyroid, spleen, mammary gland, adrenal, kidney, stomach and lung. These changes were due to hormonal disturbances or as a result of reduced food consumption or reduced incidences of pituitary, mammary or testicular tumors. This study indicates that toremifene is an efficient antiestrogen in long-term treatment, is well tolerated and has no tumorigenic potential in rats.

Safety evaluation of a lipase expressed in Aspergillus oryzae.

A programme of studies was conducted to establish the safety of a lipase artificially expressed in Aspergillus oryzae to be used in the detergent industry and as a processing aid in the baking industry. Laboratory animal studies were used to assess general and inhalation toxicity, skin sensitization, and skin and eye irritation. Its potential to cause mutagenicity and chromosomal aberrations was assessed in microbial and tissue culture in vitro studies. The pathogenicity of A. oryzae, the organism used to produce the lipase, was also assessed in laboratory animals. Basic ecotoxicity in a variety of test species was studied. General and inhalation toxicity was low. There was evidence of mild skin irritation. There was no evidence of eye irritation, skin sensitization, mutagenic potential, chromosomal aberrations, exotoxicity or notable pathogenicity. Comparison of these results with human exposure levels and previously published data indicates that the lipase appears safe for consumers in the given applications, requires no special occupational health precautions in manufacture and is of low environmental impact. Furthermore, the organism used in production of the lipase hs no notable pathogenicity.

Use of nasal valve stent with anterior rhinomanometry to quantitate nasal valve obstruction.

Some patients have increased resistance in the nasal valve area that is static and does not collapse. Anterior rhinomanometry is unable to document nasal valve disorders in these instances. A simple stent was devised to open the nasal valve area during anterior mask rhinomanometry. Three groups of subjects were studied with and without the stent. These groups were 1) patients with anatomic findings of nasal valve obstruction, 2) normal control subjects, and 3) normal control subjects with artificially created midseptal nasal obstructions. At peak inspiration the median decrease in resistance with the stent in place when compared to nonstented values was 0.91 Pa.cm-3.s-1 for group 1, 0.27 Pa.cm-3.s-1 for group 2, and 0.25 Pa.cm-3.s-1 for group 3. Comparisons using the nonparametric Wilcoxon test had a significance level of p less than .001. An easily fashioned, well-tolerated nasal valve stent can be readily incorporated in anterior mask rhinomanometry technique. With use of the stent, nasal valve obstruction can be accurately diagnosed and quantitated.

Use of the Kirschner wire for mandibular reconstruction.

An adaptation of the Kirschner wire, using tie wires for fixation of the Kirschner wire in primary mandibular reconstruction following ablative surgery, is described. Eighteen patients with a Kirschner wire serving as a prosthesis following mandibular resection were followed up. Except for three patients, who had extensive resection of the tongue, all patients were judged as having satisfactory mastication and deglutition. Only two patients required another operation for wire-related complications. The Kirschner wire, when modified as presented, proved a dependable and stable prosthesis for mandibular reconstruction.

Estrogenic potencies of resorcylic acid lactones and 17 beta-estradiol in female rats.

Uterotrophic response in sexually immature female rats has been used to rank the relative estrogenic potencies of six resorcylic acid lactones (RALs) and to compare their activities with that of 17 beta-estradiol. On oral administration, the estrogenic potency relative to 17 beta-estradiol is as follows: 7 alpha-zearalenol, 10 times less; zeranol, 150 times less; taleranol, 350 times less; zearalanone, 400 times less; zearalenone, 650 times less; 7 beta-zearalenol, 3500 times less. On subcutaneous administration, zeranol is 500 times less estrogenic than 17 beta-estradiol.

Psychogenic G-force intolerance revisited.

Three cases of psychogenic G-force intolerance are presented with a discussion of common factors. This syndrome was first described in 1958 but there has been no attention to it in the aeromedical literature since then. The significant common factor in these cases appears to be inadequate or inappropriate motivation.

Psychotherapy and return to flying duties.

The medical records of a group of 112 successive cases refered for psychiatric consultation to the USAF School of Aerospace Medicine were reviewed. Fifty-eight (52%) of these were psychiatrically disqualified but felt to be amenable to psychotherapy, which was recommended. Followup contact was possible in 49 of these cases to show that 38 did, in fact, receive treatment. Of this later group, 18 were successfully returned to flying duties along with six more, who had no formal treatment beyond several consultative visits, for a total salvage rate of 49%. Psychotherapy had previously been proven to be effective under conditions of major wartime mobilization. Its use in peacetime and during limited warfare has been studied only sparsely, except in the German Air Force, and only for specific conditions in the Royal Air Force. Results of this study support the contention that psychotherapy is feasibly effective in allowing other wise disqualified fliers to return to flying duties.