Evidence for multiple signaling pathways in single squid olfactory receptor neurons

At least two different G-protein-mediated transduction cascades, the adenylate cyclase and phospholipase C (PLC) pathway, process chemosensory stimuli for various species. In squid olfactory receptor neurons (ORNs), physiological studies indicate that both pathways may be present; however, confirmation of the transduction molecules at the protein level is absent. Here we provide evidence that the G-proteins involved in both adenylate cyclase and PLC pathways are present in squid ORNs (Lolliguncula brevis). We used immunoblotting to show that Galpha(olf), Galpha(q), and a downstream effector, enzyme PLC140, are present in the squid olfactory epithelium (OE). To localize these proteins to one or more of the five morphological cell types described for squid OE, paraformaldehyde-fixed olfactory organs were cryosectioned (10 microm), double-labeled for Galpha(olf), Galpha(q), or PLC140, and imaged. Analysis of serial sections from entire olfactory organs for epithelial area and patterns of immunofluorescence revealed a region of highest immunoreactivity at the anterior half of the organ. At the cellular level, type 1 cells could not be distinguished morphologically and were not included in the analysis. The three labeling patterns observed in type 2 cells were Galpha(q) alone, PLC140 alone, and colocalization of Galpha(q) and PLC140. Subsets of cell types 3, 4, and 5 showed colocalization of Galpha(olf) with Galpha(q) but not with PLC140. These data suggest that the PLC pathway predominates in type 2 cells; however, coexpression of Galpha(olf) with Galpha(q) in cell types 3, 4, and 5 suggests that both pathways may participate in olfactory transduction in non-type 2 squid ORNs.     

Ageing appearance in China: biophysical profile of facial skin and its relationship to perceived age

Background Perceived age is important to women and is a primary driver for topical product use and facial cosmetic surgery. Changes in facial features and biophysical skin parameters with chronological age and their associations with perceived age have not been described in Asian populations. Objective To investigate the relationship between biophysical properties of the skin, visual features of skin ageing and perceived facial age in Chinese women. Methods Facial photographs were collected of 250 Chinese women, aged 25–70 years in Shanghai, China. The perceived facial age was determined and related to the chronological age for each participant and to a range of visual assessments of skin appearance and objective biophysical measurements of the skin. The profile of changes in these parameters with age was investigated together with the differences in those parameters for women judged to look younger than their chronological age and those judged to look older than their chronological age. Results Large discrepancies in perceived age (up to 29 years) were found in women of the same chronological age. Each objective skin measure and visual assessment parameter had a stronger correlation with perceived age than with chronological age. The strongest relationships to perceived age were for wrinkles and hyperpigmentation. Skin colour, hydration and trans‐epidermal water loss (TEWL) had weaker associations with perceived age. Women judged to look older than their chronological age had significantly higher scores than those judged to look younger for coarse wrinkles and hyperpigmentation across all age groups. The appearance differences between these groups were evident in composite facial images of the same average chronological age. Conclusions We have identified the skin attributes which differ with perceived age in Chinese women. Perceived age is a better measure of the biological age of facial skin than is chronological age in this population.     

Modification of the noradrenergic cyclic AMP generating system in the rat limbic forebrain by amphetamine: Role of its hydroxylated metabolites

Summary The cyclic AMP responses to norepinephrine (NE) in slices of the rat limbic forebrain after the administration of (S)-amphetamine and the role of its para- and -hydroxylated metabolites were investigated. The chronic but not acute administration of (S)-amphetamine to rats causes a significant reduction in the sensitivity of the cyclic AMP generating system to NE without changing the basal level of the nucleotide. This change in the sensitivity of the system is not associated with a change in the EC₅₀ value for NE but reflects mainly a decrease in the maximal response. After withdrawal of the drug, the cyclic AMP response to NE returned to control values within 4 days. In vitro, (S)-p-hydroxyamphetamine (POH) and all stereoisomers of p-hydroxynorephedrine (PHN) except (S,R)-PHN enhanced the cyclic AMP response to low concentrations of NE. Since (S,R)-PHN [like the other stereoisomers of PHN and (S)-POH] inhibited in a dose-dependent manner the high affinity uptake of ³H-NE into crude synaptosomal fractions of the limbic forebrain, the results might suggest that the presumably physiological enantiomer of PHN also exerts receptor blocking properties. The inhibition by (S,R)-PHN of the cocaine induced potentiation of the cyclic AMP response to NE supports this supposition. The results provide evidence that the hydroxylated metabolites of (S)-amphetamine, (S)-POH and (S,R)-PHN, modify the action of the parent drug on central noradrenergic function at the level of the NE receptor coupled adenylate cyclase system.     

术前口服依他昔布对妇科手术后病人自控镇痛的影响

目的:观察妇科开腹手术患者术前给予依他昔布120mg对术后自控镇痛(PCA)吗啡用量的影响及其副作用。方法:随机选取全麻下接受妇科开腹全子宫(双附件)切除患者40例,术前分别给予安慰剂或依他昔布120mg口服。在手术后观察24h患者PCA吗啡用量,同时记录患者的疼痛评分和满意度评分,并观察不良反应。结果:术后PCA吗啡24h消耗量在依他昔布组为9.4±7.6mg,显著低于安慰剂组15.7±8.9mg。两组患者24h内对PCA的按压次数依他昔布组也低于安慰剂组(P<0.05)。其中术后3、6、8和12hPCA吗啡消耗量在两组间无显著差异。两组患者术后24h疼痛评分和对镇痛治疗的满意度也无差异。两组患者不良反应的发生率亦无差别。结论:在妇科开腹手术患者术前应用依他昔布120mg可使患者术后PCA吗啡消耗量降低,且在术后12h后下降明显。未发现与依他昔布应用相关的副作用。     

Implementation and evaluation of a nurse-centered computerized potassium regulation protocol in the intensive care unit - a before and after analysis

Background  

Potassium disorders can cause major complications and must be avoided in critically ill patients. Regulation of potassium in the intensive care unit (ICU) requires potassium administration with frequent blood potassium measurements and subsequent adjustments of the amount of potassium administrated. The use of a potassium replacement protocol can improve potassium regulation. For safety and efficiency, computerized protocols appear to be superior over paper protocols. The aim of this study was to evaluate if a computerized potassium regulation protocol in the ICU improved potassium regulation.     

Apparent loss and hypertrophy of interneurons in a mouse model of neuronal ceroid lipofuscinosis: evidence for partial response to insulin-like growth factor-1 treatment.

The neuronal ceroid lipofuscinoses (NCL) are progressive neurodegenerative disorders with onset from infancy to adulthood that are manifested by blindness, seizures, and dementia. In NCL, lysosomes accumulate autofluorescent proteolipid in the brain and other tissues. The mnd/mnd mutant mouse was first characterized as exhibiting adult-onset upper and lower motor neuron degeneration, but closer examination revealed early, widespread pathology similar to that seen in NCL. We used the autofluorescent properties of accumulated storage material to map which CNS neuronal populations in the mnd/mnd mouse show NCL-like pathological changes. Pronounced, early accumulation of autofluorescent lipopigment was found in subpopulations of GABAergic neurons, including interneurons in the cortex and hippocampus. Staining for phenotypic markers normally present in these neurons revealed progressive loss of staining in the cortex and hippocampus of mnd/mnd mice, with pronounced hypertrophy of remaining detectable interneurons. In contrast, even in aged mutant mice, many hippocampal interneurons retained staining for glutamic acid decarboxylase. Treatment with insulin-like growth factor-1 partially restored interneuronal number and reduced hypertrophy in some subregions. These results provide the first evidence for the involvement of interneurons in a mouse model of NCL. Moreover, our findings suggest that at least some populations of these neurons persist in a growth factor-responsive state.     

Heterogeneity in mammography use across the nation: separating evidence of disparities from the disproportionate effects of geography

Background

Mammography is essential for early detection of breast cancer and both reduced morbidity and increased survival among breast cancer victims. Utilization is lower than national guidelines, and evidence of a recent decline in mammography use has sparked concern. We demonstrate that regression models estimated over pooled samples of heterogeneous states may provide misleading information regarding predictors of health care utilization and that comprehensive cancer control efforts should focus on understanding these differences and underlying causal factors. Our study population includes all women over age 64 with breast cancer in the Surveillance Epidemiology and End Results (SEER) cancer registries, linked to a nationally representative 5% reference sample of Medicare-eligible women located in 11 states that span all census regions and are heterogeneous in racial and ethnic mix. Combining women with and without cancer in the sample allows assessment of previous cancer diagnosis on propensity to use mammography. Our conceptual model recognizes the interplay between individual, social, cultural, and physical environments along the pathways to health care utilization, while delineating local and more distant levels of influence among contextual variables. In regression modeling, we assess individual-level effects, direct effects of contextual factors, and interaction effects between individual and contextual factors.

Results

Pooling all women across states leads to quite different conclusions than state-specific models. Commuter intensity, community acculturation, and community elderly impoverishment have significant direct impacts on mammography use which vary across states. Minorities living in isolated enclaves with others of the same race/ethnicity may be either advantaged or disadvantaged, depending upon the place studied.

Conclusion

Careful analysis of place-specific context is essential for understanding differences across communities stemming from different causal factors. Optimal policy interventions to change behavior (improve screening rates) will be as heterogeneous as local community characteristics, so no "one size fits all" policy can improve population health. Probability modeling with correction for clustering of individuals within multilevel contexts can reveal important differences from place to place and identify key factors to inform targeting of specific communities for further study.