Systemic coadministration of chloramphenicol with intravenous but not intracerebroventricular morphine markedly increases morphine antinociception and delays development of antinociceptive tolerance in rats

Chloramphenicol, an in vitro inhibitor of the glucuronidation of morphine to its putative antianalgesic metabolite, morphine-3-glucuronide (M3G), was coadministered with morphine in adult male Sprague-Dawley rats to determine whether it inhibited the in vivo metabolism of morphine to M3G, thereby enhancing morphine antinociception and/or delaying the development of antinociceptive tolerance. Parenteral chloramphenicol was given acutely (3-h studies) or chronically (48-h studies). Morphine was administered by the i.v. or i.c.v. route. Control rats received chloramphenicol and/or vehicle. Antinociception was quantified using the hotplate latency test. Coadministration of chloramphenicol with i.v. but not i.cv. morphine increased the extent and duration of morphine antinociception by approximate to 5.5-fold relative to rats that received i.v. morphine alone. Thus, the mechanism through which chloramphenicol enhances i.v. morphine antinociception in the rat does not directly involve supraspinal opioid receptors. Acutely, parenteral coadministration of chloramphenicol and morphine resulted in an approximate to 75% increase in the mean area under the serum morphine concentration-time curve but for chronic dosing there was no significant change in this curve, indicating that factors other than morphine concentrations contribute significantly to antinociception. Antinociceptive tolerance to morphine developed more slowly in rats coadministered chloramphenicol, consistent with our proposal that in vivo inhibition of M3G formation would result in increased antinociception and delayed development of tolerance. However, our data also indicate that chloramphenicol inhibited the biliary secretion of M3G. Whether chloramphenicol altered the passage of M3G and morphine across the blood-brain barrier remains to be investigated.

Quantum controlled-NOT gate with 'hot' trapped ions

We present a novel method of performing quantum logic gates in trapped ion quantum computers which does not require the ions to be cooled down to the ground state of their vibrational modes, thereby avoiding one of the principal experimental difficulties encountered in realizing this technology. Our scheme employs adiabatic passages and a phase shift conditional on the phonon number state.

Calcium absorption in postmenopausal osteoporosis: Benefit of HRT plus calcitriol, but not HRT alone, in both malabsorbers and normal absorbers

In a randomized trial involving 71 postmenopausal osteoporotic women with vertebral compression fractures, radiocalcium absorption studies using the Ca-45 single isotope method (alpha) were performed at baseline and after 8 months of treatment with either continuous combined hormone replacement therapy (HRT, as piperazine estrone sulfate 0.625-0.937mg daily +/- medroxyprogesterone acetate 2.5 mg daily depending on uterine status) or HRT plus calcitriol 0.25 mu g twice daily. A calcium supplement of 600 mg nocte was given to only those women who had a daily calcium intake of less than 1 g per day at baseline, as assessed by recalled dietary intake. There was a significant decrease 0.74 (+/- 0.35 SD) to 0.58 (+/- 0.22), Delta alpha = -0.17 (+/- 0.26), p<0.0005] in alpha at 8 months compared with baseline in the HRT-treated group, but a significant increase [0.68 (+/- 0.31) to 0.84 (+/- 0.27), Delta alpha = +0.16 (+/- 0.30), p<0.003] in the HRT-plus-calcitriol treated patients, resulting in alpha being significantly higher after 8 months in the latter group than in the HRT-only group. Although 72% of the patients had been supplemented with calcium between the first and second studies, separate analyses revealed that the change in calcium intake had not affected the result. Further breakdown of the groups into baseline 'normal' absorbers (alpha greater than or equal to 0.55) and 'malabsorbers' (alpha <0.55) revealed that alpha decreased with HRT treatment only in the normal absorbers, and remained stable in the malabsorbers. Conversely, following HRT plus calcitriol treatment, alpha increased only in the malabsorbers, the normal absorbers in this group remaining unchanged. In conclusion, our data show that HRT, of the type and dose used in this study, did not produce an increase in absorption efficiency; it was in fact associated with a fall. increased absorption efficiency cannot be achieved unless calcitriol is used concurrently, and then only in patients with malabsorption. Calcitriol also had a significant effect in normal absorbers in that it prevented the decline in alpha seen with HRT alone, and thus should be considered in all patients with postmenopausal osteoporosis treated with HRT.

Which one of these is not like the others? An inter-hospital study of the viscosity of thickened fluids

Engineering This investigation examined the rheological (viscosity and yield stress) and material property (density) characteristics of the thickened meal-time and videofluorscopy fluids provided by 10 major metropolitan hospitals. Differences in the thickness of thickened fluids were considered as a source of variability and potential hazard for inter-hospital transfers of dysphagic patients. The results indicated considerable differences in the viscosity, density, and yield stress of both meal-time and videofluoroscopy fluids. In theory, the results suggest that dysphagic patients transferred between hospitals could be placed on inappropriate levels of fluid thickness because of inherent differences in the rheology and material property characteristics of the fluids provided by different hospitals. Slowed improvement or medical complications are potential worst-case scenarios for dysphagic patients if the difference between the thick fluids offered by 2 hospitals are extreme. The investigation outlines the most appropriate way to assess the rheological and material property characteristics of thickened fluids. In addition, it suggests a plan of quality improvement to reduce the variability of the thickness of fluids offered at different hospitals.

Relationships among climate, latitude and migration: Australian butterflies are not temperate-zone birds

We examined the distribution of butterflies over the mostly arid and semi-arid continent of Australia and analyzed the proportion of migrant species and species diversity with respect to an array of climatic and geographic variables. On a continent-wide scale, latitude explained virtually no variance in either proportion of migrants (r(2) = 0.01) or species diversity (r(2) = 0.03) in Australian butterflies. These results are in marked contrast to those for temperate-zone birds from three continents where latitude explained between 82 and 98% of the variance in frequency of migrants and also accounted for much of the variance in bird species diversity. In eastern Australia where rainfall regimes are similar to those in temperate Europe and North and South America, latitude explains 78% of the variance in frequency of butterfly migrants. In both eastern and central Australia, latitude also accounts for relatively high proportions of the variance in species diversity. Rainfall patterns and especially soil moisture are negatively associated with migration frequency in Australian butterfly faunas, both alone and in combination with other climate variables. Where moisture levels are relatively high, as in eastern Australia, measures of temperature are associated with migration frequency, a result consistent with findings for temperate-zone birds, suggesting latitude is a surrogate for temperature. The ultimate causes of migration in temperate-zone birds and Australian butterflies are the uneven temporal, and in Australia also spatial, distribution of resources. Uneven distribution is brought about primarily by temperature in temperate regions and by erratic rainfall over much of arid Australia. As a key determinant of productivity, especially in the tropics and subtropics, aridity is likely to be an important determinant of the global distributions of migrants.

Heterogeneous distribution of isoactins in cultured vascular smooth muscle cells does not reflect segregation of contractile and cytoskeletal domains

We have previously demonstrated that or-smooth muscle (alpha -SM) actin is predominantly distributed in the central region and beta -non-muscle (beta -NM) actin in the periphery of cultured rabbit aortic smooth muscle cells (SMCs). To determine whether this reflects a special form of segregation of contractile and cytoskeletal components in SMCs, this study systematically investigated the distribution relationship of structural proteins using high-resolution confocal laser scanning fluorescent microscopy. Not only isoactins but also smooth muscle myosin heavy chain, alpha -actinin, vinculin, and vimentin were heterogeneously distributed in the cultured SMCs. The predominant distribution of beta -NM actin in the cell periphery was associated with densely distributed vinculin plaques and disrupted or striated myosin and ol-actinin aggregates, which may reflect a process of stress fiber assembly during cell spreading and focal adhesion formation. The high-level labeling of alpha -SM actin in the central portion of stress fibers was related to continuous myosin and punctate alpha -actinin distribution, which may represent the maturation of the fibrillar structures. The findings also suggest that the stress fibers, in which actin and myosin filaments organize into sar-comere-like units with alpha -actinin-rich dense bodies analogous to Z-lines, are the contractile vimentin structures of cultured SMCs that link to the network of vimentin-containing intermediate alpha -actinin filaments through the dense bodies and dense plaques.

Exposure of rats to a high but not low dose of ethanol during early postnatal life increases the rate of loss of optic nerve axons and decreases the rate of myelination

Visual system abnormalities are commonly encountered in the fetal alcohol syndrome although the level of exposure at which they become manifest is uncertain. In this study we have examined the effects of either low (ETLD) or high dose (ETHD) ethanol, given between postnatal days 4-9, on the axons of the rat optic nerve. Rats were exposed to ethanol vapour in a special chamber for a period of 3 h per day during the treatment period. The blood alcohol concentration in the ETLD animals averaged similar to 171 mg/dl and in the ETHD animals similar to 430 mg/dl at the end of the treatment on any given day. Groups of 10 and 30-d-old mother-reared control (MRC), separation control (SC), ETLD and ETHD rats were anaesthetised with an intraperitoneal injection or ketamine and xylazine, and killed by intracardiac perfusion with phosphate-buffered glutaraldehyde. In the 10-d-old rat optic nerves there was a total of similar to 145000-165000 axons in MRC, SC and ETLD animals. About 4 % of these fibres were myelinated. The differences between these groups were not statistically significant. However, the 10-d-old ETHD animals had only about 75000 optic nerve axone (P < 0.05) of which about 2.8 % were myelinated. By 30 d of age there was a total of between 75000 90000 optic nerve axons, irrespective of the group examined. The proportion of axons which were myelinated at this age was still significantly lower (P < 0.001) in the ETHD animals (similar to 77 %) than in the other groups (about 98 %). It is concluded that the normal stages of development and maturation of the rat optic nerve axons, as assessed in this study, can be severely compromised by exposure to a relatively high (but not low) dose of ethanol between postnatal d 4 and 9.

Recombinant human growth hormone, but not insulin-like growth factor-I, enhances central fat loss in postmenopausal women undergoing a diet and exercise program

We examined the effect of recombinant human growth hormone (rhGH) and/or recombinant human insulin-like growth factor-I (rhIGF-I) on regional fat loss in postmenopausal women undergoing a weight loss regimen of diet plus exercise. Twenty-seven women aged 59-79 years, 20-40% above ideal body weight, completed a 12-week program consisting of resistance training 2 days/week and walking 3 days/week, while consuming a diet that was 500 kcal/day less than that required for weight maintenance, Participants were randomly assigned in a double-blind fashion to receive rhGH (0.025 mg/kg BW/day: n=7), rhIGF-I (0.015 mg/kg BW/day: n=7), rhGH + rhIGF-I (n = 6), or placebo (PL: n = 7). Regional and whole body fat mass were determined by dual X-ray absorptiometry. Body fat distribution was assessed by the ratios of trunk fat-to-limb fat (TrF/LimbF) and trunk fat-to-total fat (TrF/TotF), Limb and trunk fat decreased in all groups (p < 0.01). For both ratios of fat distribution, the rhGH treated group experienced an enhanced loss of truncal compared to peripheral fat (p less than or equal to 0.01), with no significant change for those administered rhIGF-I or FL. There was no association between change in fat distribution and indices of cardiovascular disease risk as determined by serum lipid/lipoprotein levels and maximal aerobic capacity. These results suggest that administration of rhGH facilitates a decrease in central compared to peripheral fat in older women undertaking a weight loss program that combines exercise and moderate caloric restriction, although no beneficial effects are conferred to lipid/lipoprotein profiles, Further, the effect of rhGH is not enhanced by combining rhCH with rhIGF-I administration. In addition, rhIGF-I does not augment the loss of trunk fat when administered alone.

Biological control of the rabbit in Australia: lessons not learned?

The story of the spread of the European rabbit across Australia, and of the two viruses used to control it, is an interesting way to look at some of the issues associated with biological control. What can be learned from the way this system developed, and what has been learned, or not learned, from the mistakes made? Here, we look at these events and examine what insights can be gained from this history.

Decreased perinatal sunshine duration is associated with increased non-affective but not affective psychosis birth rates

We have previously found an association between variations in schizophrenia birth rates and varyinglevels of perinatal sunshine duration. This study examines whether such an association can also be found for Ža. affective psychosis, and Žb. broadly defined nonaffective psychoses. Data for individuals born between 1931 and 1970 in Australia with ICD9 Other PsychosisŽ295–299.were obtained from the Queensland Mental Health Statistical System. ‘Affective psychosis’ included affective psychosis, schizo-affective psychosis, and depressive and excitative non-organic psychoses. ‘Non-affective psychosis’ included chizophrenia, paranoid disorders and other non-organic psychoses. Those receiving both affective and non-affective psychotic diagnoses were excluded. Rates per 10,000 live monthly general population births were calculated. For each month, we assessed the agreementŽusing the kappa statistic. between trends in Ža. birth rates and Žb. long-term trends in seasonally adjusted perinatal sunshine duration. The analyses were performed separately for males and females. There were 6265 with non-affective psychosis ŽMs3964 rate 66r10,000; Fs2299 44r10,000. and 2858 with affective psychosisŽMs1392 24r10,000; Fs1466 28r10,000.. There were no significant associations between Ža. affective psychosis birth rates for either males or females and Žb. sunshine duration. There was a significant association between nonaffective psychosis birth rates for males only and Žb. sunshine duration Žkappas0.15 p-0.001.. This suggests that, as a risk factor, the effect of reduced perinatal sunshine is specifically associated with males who develop non-affective psychosis. The Stanley Foundation supported this project.